A Phase 3, Randomized, Open-label, Multicenter Clinical Study to Evaluate the Safety and Efficacy of MK-1084, Cetuximab, and mFOLFOX6 Versus mFOLFOX6 With or Without Bevacizumab as First-line Treatment of Participants With KRAS G12C-mutant, Locally Advanced Unresectable or Metastatic Colorectal Cancer (KANDLELIT-012)

Researchers are looking for other ways to treat locally advanced or metastatic colorectal cancer (mCRC) that is unresectable and has a gene mutation called KRAS G12C.
Standard (or usual) treatments for this type of colorectal cancer may include mFOLFOX6 with or without bevacizumab. Researchers want to learn if adding MK-1084 (the study medicine) and cetuximab to mFOLFOX6 can treat locally advanced or mCRC with the KRAS G12C mutation. MK-1084 and cetuximab are targeted therapies.
The goals of this study are to learn:
* About the safety of MK-1084 with cetuximab and mFOLFOX6 and if people tolerate the treatments
* If people who receive MK-1084 with cetuximab and mFOLFOX6 live longer without mCRC growing or spreading compared to people who receive mFOLFOX6 with or without bevacizumab.

Start Date16 Jul 2025

Sponsor / Collaborator

Merck Sharp & Dohme LLC

NCT06942741

/ Active, not recruitingPhase 1

A Two-Part Study to Determine Bioequivalence Between the MK-1084 Film-Coated Tablet and Oral-Compressed Tablet and the Effect of Food on the Single-Dose Pharmacokinetics of the MK-1084 Film-Coated Tablet in Healthy Adult Participants

This study has 2 parts. Researchers want to learn what happens to MK-1084 in a healthy person's body over time in both parts. The goals of the study are:
* In Part 1, to compare what happens to MK-1084 in a person's blood when it is taken as 2 different types of oral tablets
* In Part 2, to learn what happens to MK-1084 in a person's blood when it is taken on an empty stomach or after a meal

Start Date13 May 2025

Sponsor / Collaborator

Merck Sharp & Dohme LLC

NCT06814119

/ RecruitingPhase 1

A Clinical Study to Evaluate the Effect of Renal Impairment on the Single-Dose Pharmacokinetics of MK-1084

The goal of this study is to learn what happens to MK-1084 levels in a person's body over time. Researchers will measure what happens to MK-1084 levels in the body when it is given to people with moderate or severe renal impairment (RI) (meaning the kidneys do not work properly) as compared to people who are in good health. Researchers also want to learn about the safety of MK-1084 when it is given to people with RI and if people with RI can tolerate it.

Start Date07 Apr 2025

Sponsor / Collaborator

Merck Sharp & Dohme LLC

100 Clinical Results associated with MK-1084

100 Translational Medicine associated with MK-1084

100 Patents (Medical) associated with MK-1084

Literatures (Medical) associated with MK-1084

01 Oct 2024·PATHOLOGY

The histopathological spectrum and molecular changes associated with KRAS G12C mutation in non-small cell lung carcinoma

Article

Author: Cooper, Wendy A ; Li, Jing Jing ; Williamson, Jonathan ; Ding, Pei ; French, Bruce ; Yip, Po Yee ; Chua, Wei ; Vinod, Shalini ; Hagelamin, Abeer ; Gupta, Ruta ; Bray, Victoria ; Wu, Xiao Juan ; Lee, C Soon ; Farzin, Mahtab ; Nindra, Udit ; Pal, Abhijit ; Wang, Bin

KRAS G12C is the most common KRAS mutation in non-small cell lung carcinoma (NSCLC), for which targeted therapy has recently been developed. From the 732 cases of NSCLC that underwent next-generation sequencing at the Department of Anatomical Pathology, Liverpool Hospital, between July 2021 and May 2023, we retrieved 83 (11%) consecutive cases of KRAS G12C mutated NSCLC, and analysed their clinical, pathological, and molecular features. Of the 83 cases of KRAS G12C mutated NSCLC, there were 46 (55%) men and 37 (45%) women, with mean age of 72 years. Of the 49 cases with known clinical information, 94% were current or ex-smokers, and 49% were stage IV at diagnosis with median survival of 12 months. Sixty-three percent were histology cases and the remainder were cytology cases. Eighty-two percent were non-mucinous adenocarcinomas, with conventional histology including lepidic, acinar, solid, single cells and micropapillary patterns, and 62% were poorly differentiated. There were five (6%) cases of mucinous adenocarcinoma, one case of pleomorphic carcinoma and one case of high-grade fetal adenocarcinoma. TTF1 was positive in the majority (89%) of cases. Nineteen (23%) cases had TP53 co-mutation, and these cases had trends towards higher PD-L1 expression, poor differentiation, and presentation as stage IV disease, but the differences were not statistically significant. KRAS G12C mutated NSCLCs almost exclusively occurred in smokers and were mostly non-mucinous adenocarcinomas with conventional histological patterns which ranged from well to poorly differentiated. Around a quarter had TP53 co-mutation, the histological impacts and immune profile of which need to be assessed in a larger study.

11 Jul 2024·JOURNAL OF MEDICINAL CHEMISTRY

Discovery of MK-1084: An Orally Bioavailable and Low-Dose KRAS^G12C Inhibitor

Article

Author: Munsell, Erik V. ; Day, Phil J. ; Sather, Aaron C. ; Han, Yongxin ; Orth, Peter ; Sloman, David L. ; Duggal, Ruchia ; Rankic, Danica A. ; Miller, Richard ; Lyons, Thomas W. ; Song, Xuelei Sherry ; Yang, Yi ; Anderson, Kenneth D. ; Solban, Nicolas ; Wen, Xin ; Ballard, Jeanine E. ; Yang, Ruojing ; Ma, Xiaoshen ; Xu, Zangwei ; Gathiaka, Symon ; Brynczka, Christopher ; Stoeck, Alexander ; Henderson, Timothy J. ; Otte, Ryan D. ; Robinson, Michelle R. ; Bennett, David Jonathan ; Palani, Anandan ; Bharathan, Indu

Oncogenic mutations in the RAS gene account for 30% of all human tumors; more than 60% of which present as KRAS mutations at the hotspot codon 12. After decades of intense pursuit, a covalent inhibition strategy has enabled selective targeting of this previously "undruggable" target. Herein, we disclose our journey toward the discovery of MK-1084, an orally bioavailable and low-dose KRAS^G12C covalent inhibitor currently in phase I clinical trials (NCT05067283). We leveraged structure-based drug design to identify a macrocyclic core structure, and hypothesis-driven optimization of biopharmaceutical properties to further improve metabolic stability and tolerability.

12 Aug 2021·ACS medicinal chemistry letters

Small Molecule Inhibitors of KRAS G12C Mutant

Author: Kargbo, Robert B.

The present Patent Highlight relates to certain cyclic heteroaryl compounds and pharmaceutically acceptable salts that inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein.These compounds have utility as therapeutic agents for the treatment of cancer and is related to the recent disclosure by the applicant in ACS Med. Chem. Lett. 2021,https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00321.

News (Medical) associated with MK-1084

29 Jul 2025

·www.merck.com

Merck & Co., Inc., Rahway, N.J., USA Announces Second-Quarter 2025 Financial Results

July 29, 2025 6:30 am ET Total Worldwide Sales Were $15.8 Billion, a Decrease of 2% From Second Quarter 2024 Both Nominally and Excluding the Impact of Foreign Exchange KEYTRUDA Sales Were $8.0 Billion, Growth of 9% Both Nominally and Excluding the Impact of Foreign Exchange WINREVAIR Sales Were $336 Million Animal Health Sales Were $1.6 Billion, Growth of 11% Both Nominally and Excluding the Impact of Foreign Exchange GARDASIL/GARDASIL 9 Sales Were $1.1 Billion, a Decline of 55% Both Nominally and Excluding the Impact of Foreign Exchange GAAP EPS Was $1.76; Non-GAAP EPS Was $2.13; GAAP and Non-GAAP EPS Include a Charge of $0.07 per Share for Closing of Hengrui Pharma License Agreement Announced Agreement To Acquire Verona Pharma and Its First-In-Class COPD Maintenance Treatment for Adults, Ohtuvayre®;1 Transaction Expected To Close in Fourth Quarter 2025 Announced Positive Topline Results From First Two Phase 3 CORALreef Trials of Enlicitide Decanoate for Treatment of Adults With Hyperlipidemia Received FDA Approval of ENFLONSIA for Prevention of RSV Lower Respiratory Tract Disease in Infants Born During or Entering Their First RSV Season; CDC’s ACIP Recommended ENFLONSIA for Prevention of RSV in Infants Younger Than 8 Months of Age for Their First RSV Season Announced Multiyear Optimization Initiative Anticipated To Result in Approximately $3.0 Billion of Annual Cost Savings by the End of 2027, To Be Fully Reinvested Into Strategic Growth Areas Full-Year 2025 Financial Outlook Narrows Expected Worldwide Sales Range To Be Between $64.3 Billion and $65.3 Billion Narrows Expected Non-GAAP EPS Range To Be Between $8.87 and $8.97 Outlook Does Not Include Anticipated Impact of the Announced Acquisition of Verona Pharma KEYTRUDA Sales Were $8.0 Billion, Growth of 9% Both Nominally and Excluding the Impact of Foreign Exchange WINREVAIR Sales Were $336 Million Animal Health Sales Were $1.6 Billion, Growth of 11% Both Nominally and Excluding the Impact of Foreign Exchange GARDASIL/GARDASIL 9 Sales Were $1.1 Billion, a Decline of 55% Both Nominally and Excluding the Impact of Foreign Exchange Narrows Expected Worldwide Sales Range To Be Between $64.3 Billion and $65.3 Billion Narrows Expected Non-GAAP EPS Range To Be Between $8.87 and $8.97 Outlook Does Not Include Anticipated Impact of the Announced Acquisition of Verona Pharma RAHWAY, N.J.--(BUSINESS WIRE)-- Merck & Co., Inc., Rahway, N.J., USA (NYSE: MRK), known as MSD outside the United States and Canada, today announced financial results for the second quarter of 2025. "Earlier this month, we were pleased to announce our pending acquisition of Verona Pharma, which augments our portfolio and pipeline and is another example of acting decisively when science and value align,” said Robert M. Davis, chairman and chief executive officer. “Today, we announced a multiyear optimization initiative that will redirect investment and resources from more mature areas of our business to our burgeoning array of new growth drivers, further enable the transformation of our portfolio, and drive our next chapter of productive, innovation-driven growth. With these actions, I am confident that we are well positioned to generate near- and long-term value for our shareholders and, most importantly, deliver for our patients.” Financial Summary $ in millions, except EPS amounts Second Quarter 2025 2024 Change Change Ex- Exchange Sales $15,806 $16,112 -2% -2% GAAP net income2 4,427 5,455 -19% -17% Non-GAAP net income that excludes certain items2,3* 5,366 5,809 -8% -6% GAAP EPS 1.76 2.14 -18% -16% Non-GAAP EPS that excludes certain items3* 2.13 2.28 -7% -5% *Refer to table on page 7. For the second quarter of 2025, Generally Accepted Accounting Principles (GAAP) earnings per share (EPS) assuming dilution was $1.76 and non-GAAP EPS was $2.13. GAAP and non-GAAP EPS in the second quarter of 2025 include a charge of $0.07 per share for an upfront payment to Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma) upon closing of a license agreement. Non-GAAP EPS excludes acquisition- and divestiture-related costs, costs related to restructuring programs, and income and losses from investments in equity securities. Non-GAAP EPS in the second quarter of 2025 also excludestax benefits primarily resulting from favorable audit adjustments. Non-GAAP EPS in the second quarter of 2024 also excludes a tax benefit due to a reduction in reserves for unrecognized income tax benefits, resulting from the expiration of the statute of limitations for assessments related to the 2019 federal tax return year. Year-to-date results can be found in the attached tables. Second-Quarter Sales Performance The following table reflects sales of the Company’s top products and significant performance drivers. Second Quarter $ in millions 2025 2024 Change Change Ex- Exchange Commentary Total Sales $15,806 $16,112 -2% -2% Pharmaceutical 14,050 14,408 -2% -3% Decline primarily due to vaccines and immunology, partially offset by growth in oncology and cardiology. KEYTRUDA 7,956 7,270 9% 9% Growth driven by continued strong global demand from metastatic indications, including bladder, endometrial and gastric cancers, and increased global uptake in earlier-stage indications, including triple-negative breast cancer, renal cell carcinoma (RCC) and cervical cancer, as well as non-small cell lung cancer in the U.S. GARDASIL/GARDASIL 9 1,126 2,478 -55% -55% Decline primarily due to lower demand in China. Excluding China, sales declined 3%, or 4% excluding impact of foreign exchange, reflecting lower demand in Japan following a national catch-up immunization program, as well as timing of public-sector purchases in certain international markets. U.S. sales increased 2% in the quarter. JANUVIA/JANUMET 623 629 -1% - Decrease primarily attributable to lower demand in China, impacts of generic competition in most international markets, and lower demand in the U.S. due to competitive pressure, which were largely offset by higher net pricing in the U.S. PROQUAD, M-M-R II and VARIVAX 609 617 -1% -2% Decrease primarily reflects lower U.S. sales due to unfavorable VARIVAX public-sector activity and M-M-R II private-sector buy-out, partially offset by partial replenishment of PROQUAD doses borrowed from the U.S. Centers for Disease Control and Prevention (CDC) Pediatric Vaccine Stockpile, and higher pricing. BRIDION 461 455 1% 1% Increase primarily due to higher demand in the U.S., partially offset by lower demand in most international markets due to ongoing generic competition. Lynparza* 370 317 17% 15% Growth primarily due to higher demand in the U.S. and certain international markets. WINREVAIR 336 70 N/M N/M Growth reflects continued uptake since second-quarter 2024 launch in the U.S. Lenvima* 265 249 6% 5% Increase primarily due to higher sales in the U.S. reflecting higher demand, partially offset by lower pricing. VAXNEUVANCE 229 189 21% 20% Growth primarily due to favorable public-sector activity in the U.S. and increased demand in certain international markets, partially offset by lower demand in the U.S. and Japan due to competitive pressure. PREVYMIS 228 188 21% 20% Growth primarily due to higher demand in the U.S. and Europe, partially offset by lower demand in China due to generic competition. WELIREG 162 126 29% 29% Growth primarily driven by higher demand in the U.S. and early launch uptake in certain EU markets, partially offset by lower pricing in the U.S. CAPVAXIVE 129 - - - Represents continued uptake since third-quarter 2024 launch in the U.S. SIMPONI - 172 -100% -100% Marketing rights in former territories of the Company reverted to Johnson & Johnson on Oct. 1, 2024. Animal Health 1,646 1,482 11% 11% Growth primarily due to higher demand for Livestock products, as well as inclusion of sales from Elanco aqua business acquired in July 2024, higher pricing and improved supply. Livestock 961 837 15% 16% Growth primarily driven by higher demand across all species, as well as inclusion of sales from Elanco aqua business acquired in July 2024. Companion Animal 685 645 6% 6% Increase primarily driven by higher pricing. Sales of BRAVECTO were $335 million and $331 million in current and prior year quarters, respectively, which represents an increase of 1%, both nominally and excluding impact of foreign exchange. Other Revenues** 110 222 -50% -3% Primarily due to unfavorable impact of revenue-hedging activities. *Alliance revenue for this product represents the Company’s share of profits, which are product sales net of cost of sales and commercialization costs. **Other revenues are comprised primarily of revenues from third-party manufacturing arrangements and miscellaneous corporate revenues, including revenue-hedging activities. N/M- Not meaningful. Second-Quarter Expense, EPS and Related Information The table below presents selected expense information. $ in millions GAAP Acquisition- and Divestiture- Related Costs4 Restructuring Costs (Income) Loss From Investments in Equity Securities Non- GAAP3 Second Quarter 2025 Cost of sales $3,557 $576 $165 $- $2,816 Selling, general and administrative 2,649 15 1 - 2,633 Research and development 4,048 3 53 - 3,992 Restructuring costs 560 - 560 - - Other (income) expense, net (7) - - (61) 54 Second Quarter 2024 Cost of sales $3,745 $606 $66 $- $3,073 Selling, general and administrative 2,739 24 31 - 2,684 Research and development 3,500 20 - - 3,480 Restructuring costs 80 - 80 - - Other (income) expense, net 42 (17) - (49) 108 GAAP Expense, EPS and Related Information Gross margin was 77.5% for the second quarter of 2025 compared with 76.8% for the second quarter of 2024. The increase was primarily due to the favorable impact of product mix, partially offset by higher restructuring costs and inventory write-offs. Selling, general and administrative (SG&A) expenses were $2.6 billion in the second quarter of 2025, a decrease of 3% compared with the second quarter of 2024. The decrease was primarily due to lower administrative, restructuring and promotional costs. Research and development (R&D) expenses were $4.0 billion in the second quarter of 2025, an increase of 16% compared with the second quarter of 2024. The increase was primarily due to a $200 million charge for an upfront payment made in the second quarter of 2025 for a license agreement with Hengrui Pharma, increased clinical development spending, higher compensation and benefit costs, and higher restructuring costs. Other (income) expense, net, was $7 million of income in the second quarter of 2025 compared with $42 million of expense in the second quarter of 2024. The effective tax rate of 11.4% for the second quarter of 2025 includes a 2.9 percentage point favorable impact due to tax benefits primarily resulting from favorable audit adjustments. GAAP EPS was $1.76 for the second quarter of 2025 compared with $2.14 for the second quarter of 2024. The decrease reflects increased operating expenses driven by higher restructuring costs and research and development spending, a charge related to the closing of a license agreement with Hengrui Pharma, unfavorable tax impacts, and the unfavorable impact of foreign exchange. Non-GAAP Expense, EPS and Related Information Non-GAAP gross margin was 82.2% for the second quarter of 2025 compared with 80.9% for the second quarter of 2024. The increase was primarily due to the favorable impact of product mix, partially offset by higher inventory write-offs. Non-GAAP SG&A expenses were $2.6 billion in the second quarter of 2025, a decrease of 2% compared with the second quarter of 2024. The decrease was primarily due to lower administrative and promotional costs. Non-GAAP R&D expenses were $4.0 billion in the second quarter of 2025, an increase of 15% compared with the second quarter of 2024. The increase was primarily due to a $200 million charge for an upfront payment made in the second quarter of 2025 for a license agreement with Hengrui Pharma, increased clinical development spending, and higher compensation and benefit costs. Non-GAAP other (income) expense, net, was $54 million of expense in the second quarter of 2025 compared with $108 million of expense in the second quarter of 2024. The non-GAAP effective tax rate was 15.0% for the second quarter of 2025. Non-GAAP EPS was $2.13 for the second quarter of 2025 compared with $2.28 for the second quarter of 2024. The decrease reflects increased operating expenses driven by higher research and development spending, a charge related to the closing of a license agreement with Hengrui Pharma, and the unfavorable impact of foreign exchange. A reconciliation of GAAP to non-GAAP net income and EPS is provided in the table that follows. Second Quarter $ in millions, except EPS amounts 2025 2024 EPS GAAP EPS $1.76 $2.14 Difference 0.37 0.14 Non-GAAP EPS that excludes items listed below3 $2.13 $2.28 Net Income GAAP net income2 $4,427 $5,455 Difference 939 354 Non-GAAP net income that excludes items listed below2,3 $5,366 $5,809 Excluded Items: Acquisition- and divestiture-related costs4 $594 $633 Restructuring costs 779 177 Income from investments in equity securities (61) (49) Decrease to net income before taxes 1,312 761 Estimated income tax (benefit) expense5 (373) (407) Decrease to net income $939 $354 Planned Acquisition of Verona Pharma On July 9, 2025, the Company furthered its science-led business development strategy by announcing an agreement under which the Company, through a subsidiary, will acquire Verona Pharma plc (Verona Pharma) for $107 per American Depository Share, each of which represents eight Verona Pharma ordinary shares, for a total transaction value of approximately $10 billion. Through the acquisition, the Company will add Ohtuvayre, a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 (PDE3 and PDE4), to its growing cardio-pulmonary pipeline and portfolio. The U.S. Food and Drug Administration (FDA) approved Ohtuvayre in June 2024 for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. It is the first novel inhaled mechanism for the treatment of COPD in more than 20 years. The transaction is anticipated to close in the fourth quarter of 2025. Pipeline and Portfolio Highlights In the second quarter, the Company continued to advance its broad and diverse pipeline with multiple regulatory and clinical milestones. In oncology, the FDA approved KEYTRUDA as part of a therapy regimen for the treatment of certain adult patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC), based on results from the Phase 3 KEYNOTE-689 trial. This approval is the first perioperative anti-PD-1 treatment regimen for adults with resectable locally advanced HNSCC whose tumors express PD-L1 (CPS ≥1). In addition, the Ministry of Health, Labor and Welfare (MHLW) in Japan approved WELIREG as monotherapy for the treatment of adults with von Hippel-Lindau (VHL) disease-associated tumors, and for adults with unresectable or metastatic RCC that has progressed after chemotherapy. At the 2025 American Society of Clinical Oncology Annual Meeting, the Company announced new research across more than 25 types of cancer in multiple treatment settings. Data were presented for several candidates, including MK-1084, an investigational oral selective KRAS G12C inhibitor, and from the Company’s pipeline of antibody-drug conjugates (ADCs). The Company also presented data from Phase 3 trials evaluating new combination regimens with KEYTRUDA, and longer-term data for studies of KEYTRUDA and WELIREG, with the KEYTRUDA studies including people with earlier stages of cancer. The Company announced results from the Phase 3 KEYNOTE-B96 trial (also known as ENGOT-ov65) evaluating KEYTRUDA plus chemotherapy, which met its primary endpoint of progression-free survival (PFS) for the treatment of patients with platinum-resistant recurrent ovarian cancer whose tumors express PD-L1 and in all comers, as well as a secondary endpoint of overall survival (OS) in patients whose tumors express PD-L1. In addition, a pre-specified interim analysis of the Phase 3 KEYNOTE-937 study found that compared to placebo, KEYTRUDA did not show a statistically significant improvement in the primary endpoint of recurrence-free survival for certain patients with hepatocellular carcinoma. Also, a pre-specified interim analysis of the Phase 3 LEAP-014 trial found that KEYTRUDA plus Lenvima, in combination with platinum-based chemotherapy, did not show a statistically significant improvement in its primary endpoint of OS compared to KEYTRUDA plus chemotherapy for the first-line treatment of patients with metastatic esophageal squamous cell carcinoma (ESCC). In vaccines and infectious diseases, the Company received FDA approval of ENFLONSIA for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants who are born during or entering their first RSV season. ENFLONSIA is the first and only RSV preventive option administered to infants using the same dose regardless of weight. The CDC’s Advisory Committee on Immunization Practices (ACIP) also recommended ENFLONSIA for the prevention of RSV in infants younger than 8 months of age born during or entering their first RSV season. In addition, the Company announced initiation of the MOBILIZE-1 Phase 3 trial evaluating V181, an investigational single-dose quadrivalent vaccine for the prevention of dengue disease. In addition, the FDA accepted a New Drug Application (NDA) for doravirine/islatravir, an investigational, once-daily, oral, two-drug regimen for the treatment of adults with virologically suppressed HIV-1 based on the Phase 3 MK-8591A-051 and MK-8591A-052 trials. The FDA set a Prescription Drug User Fee Act (PDUFA) date of April 28, 2026. The Company also announced the initiation of the EXPrESSIVE Phase 3 trials for MK-8527, its investigational once-monthly oral candidate for HIV pre-exposure prophylaxis (PrEP). In cardiovascular disease, the Company announced positive topline results from Phase 3 CORALreef HeFH and CORALreef AddOn, the first two of three Phase 3 clinical trials evaluating the safety and efficacy of enlicitide decanoate, an investigational, oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor being evaluated for the treatment of adults with hyperlipidemia already on lipid-lowering therapies, including at least a statin. In both trials, enlicitide demonstrated statistically significant and clinically meaningful reductions in low-density lipoprotein cholesterol. If approved, it would be the first marketed oral PCSK9 inhibitor. In addition, the FDA granted priority review for a new supplemental Biologics License Application for WINREVAIR seeking approval to update the U.S. product label based on compelling results from the Phase 3 ZENITH trial. The FDA has set a PDUFA date of Oct. 25, 2025. The Company also provided an update on the Phase 3 HYPERION study evaluating WINREVAIR in recently diagnosed adults with pulmonary arterial hypertension (PAH). In the study, WINREVAIR added on top of background therapy within 12 months after initial diagnosis of PAH demonstrated a statistically significant and clinically meaningful reduction in the risk of clinical worsening events when compared to placebo. Further, the MHLW in Japan approved sotatercept for the treatment of adults with PAH under the trademark AIRWIN. It is the first activin signaling inhibitor therapy for PAH approved in Japan. In the Animal Health business, the FDA approved BRAVECTO QUANTUM, an injectable formulation of BRAVECTO for dogs for the treatment and persistent killing of fleas and ticks. In addition, the European Commission (EC) approved NUMELVI tablets for dogs, a once-daily, second-generation Janus kinase (JAK) inhibitor, indicated for the treatment of pruritus associated with allergic dermatitis including atopic dermatitis and treatment of clinical manifestations of atopic dermatitis. Notable recent news releases on the Company’s pipeline and portfolio are provided in the table that follows. Visit the News Releases section of the Company’s website to read the releases*. Oncology FDA Approved KEYTRUDA for PD-L1+ Resectable Locally Advanced HNSCC as Neoadjuvant Treatment, Continued as Adjuvant Treatment Combined With Radiotherapy With or Without Cisplatin Then as a Single Agent; Based on Results From Phase 3 KEYNOTE-689 Trial FDA Approved WELIREG for Treatment of Adults and Pediatric Patients 12 Years and Older With Locally Advanced, Unresectable, or Metastatic Pheochromocytoma or Paraganglioma; Based on Results From Phase 2 LITESPARK-015 Clinical Trial Phase 3 KEYNOTE-B96 Trial Met Primary Endpoint of PFS in Patients With Platinum-Resistant Recurrent Ovarian Cancer Whose Tumors Expressed PD-L1 and in All Comers KEYTRUDA Plus Trodelvy Reduced Risk of Disease Progression or Death by 35% Versus KEYTRUDA Plus Chemotherapy in First-Line PD-L1+ Metastatic Triple-Negative Breast Cancer; Based on Results From Phase 3 ASCENT-04/KEYNOTE-D19 Trial MK-1084, an Investigational KRAS G12C Inhibitor, Showed Antitumor Activity in Phase 1 Trial of Patients With Advanced Colorectal Cancer and Non-Small Cell Lung Cancer Whose Tumors Harbor KRAS G12C Mutations Investigational Zilovertamab Vedotin at 1.75 mg/kg Dose Plus Standard of Care Showed Promising Antitumor Activity, Including Complete Response Rate, in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma; Based on Results From Phase 2 WaveLINE-003 Trial IDeate-Prostate01 Phase 3 Trial of Ifinatamab Deruxtecan Initiated in Patients With Pretreated Metastatic Castration-Resistant Prostate Cancer IDeate-Esophageal01 Phase 3 Trial of Ifinatamab Deruxtecan Initiated in Certain Patients With Pretreated Advanced or Metastatic ESCC Vaccines and Infectious Diseases FDA Approved ENFLONSIA for Prevention of RSV Lower Respiratory Tract Disease in Infants Born During or Entering Their First RSV Season; Based on Results From Phase 2b/3 CLEVER Trial ACIP Recommended Use of ENFLONSIA for Prevention of RSV Lower Respiratory Tract Disease in Infants Younger Than 8 Months of Age Born During or Entering Their First RSV Season FDA Accepted NDA for Doravirine/Islatravir, an Investigational, Once-Daily, Oral, Two-Drug Regimen for Treatment of Adults With Virologically Suppressed HIV-1; Based on Results From Phase 3 MK-8591A-051 and MK-8591A-052 Trials; FDA Set PDUFA Date of April 28, 2026 EXPrESSIVE Phase 3 Trials Initiated for Investigational Once-Monthly HIV Prevention Pill, MK-8527 The Company Initiated MOBILIZE-1 Phase 3 Study Evaluating Dengue Vaccine Candidate Cardiovascular FDA Granted Priority Review for WINREVAIR to Update Label Based on Results From ZENITH Trial; FDA Set PDUFA Date of Oct. 25, 2025 The Company Announced Positive Topline Results From First Two Phase 3 CORALreef Trials Evaluating Enlicitide Decanoate for the Treatment of Adults With Hyperlipidemia Phase 3 HYPERION Study of WINREVAIR Met Primary Endpoint in Recently Diagnosed Adults With PAH Animal Health FDA Approved BRAVECTO QUANTUM EC Approved NUMELVI Tablets for Dogs *References to the Company’s name in the above news release titles have been modified for the purpose of this announcement. New Multiyear Optimization Initiative, Which Includes a Restructuring Program The Company launched a new multiyear optimization initiative to enable the transformation of its portfolio by generating an expected $3.0 billion in annual cost savings from productivity actions, which will be fully reinvested to support new product launches and its pipeline across multiple therapeutic areas. In July 2025, as part of this initiative, the Company approved a new restructuring program, in which it expects to eliminate certain administrative, sales and R&D positions. The Company will, however, continue to hire employees into new roles across strategic growth areas of the business. In addition, the Company will reduce its global real estate footprint and continue to optimize its manufacturing network, aligning the geography of its global manufacturing to its customers and reflecting changes in the Company’s business. The Company anticipates cumulative pretax costs related to the program to be approximately $3.0 billion. For the second quarter of 2025, the Company recorded charges in its GAAP results of $649 million related to this restructuring program. The Company expects the actions under the restructuring program to result in annual cost savings of approximately $1.7 billion, which will be substantially realized by the end of 2027. This restructuring program is part of the multiyear optimization initiative expected to achieve $3.0 billion in annual cost savings by the end of 2027. Manufacturing and R&D Investment The Company continued to make long-term investments in its U.S. manufacturing and R&D capabilities. This includes the start of construction for a $1.0 billion, 470,000-square-foot state-of-the-art biologics center of excellence in Wilmington, Delaware, which will serve as a launch and commercial production facility and the primary U.S. manufacturing site for KEYTRUDA. In addition, the Company announced an $895 million expansion of its Animal Health manufacturing facility in De Soto, Kansas; the 200,000-square-foot facility will increase capacity for Animal Health vaccines and biologic products. Full-Year 2025 Financial Outlook The following table summarizes the Company’s full-year financial outlook. Full Year 2025 Updated Prior Sales* $64.3 billion to $65.3 billion $64.1 billion to $65.6 billion Non-GAAP Gross margin3 Approximately 82% Approximately 82% Non-GAAPOperating expenses3** $25.6 billion to $26.4 billion $25.6 billion to $26.6 billion Non-GAAPOther (income) expense, net3 $300 million to $400 million expense $300 million to $400 million expense Non-GAAPEffective tax rate3 15.0% to 16.0% 15.5% to 16.5% Non-GAAPEPS3*** $8.87 to $8.97 $8.82 to $8.97 Share count (assuming dilution) Approximately 2.51 billion Approximately 2.51 billion *The Company does not have any non-GAAP adjustments to sales. **Includes one-time R&D charges of $300 million for a milestone payment to LaNova Medicines Ltd. (LaNova) associated with the technology transfer for MK-2010 expected to be recorded in the third quarter of 2025 and $200 million for the upfront payment for the license agreement completed with Hengrui Pharma in the second quarter of 2025. Outlook does not assume any additional significant potential business development transactions. ***Includes one-time charges totaling $0.16 per share associated with the payment for the LaNova technology transfer for MK-2010 and upfront payment to Hengrui Pharma. The Company has not provided a reconciliation of forward-looking non-GAAP gross margin, non-GAAP operating expenses, non-GAAP other (income) expense, net, non-GAAP effective tax rate and non-GAAP EPS to the most directly comparable GAAP measures, given it cannot predict with reasonable certainty the amounts necessary for such a reconciliation, including intangible asset impairment charges, legal settlements, and income and losses from investments in equity securities either owned directly or through ownership interests in investment funds, without unreasonable effort. These items are inherently difficult to forecast and could have a significant impact on the Company’s future GAAP results. The Company now expects full-year 2025 sales to be between $64.3 billion and $65.3 billion, including a revised negative impact of foreign exchange of approximately 0.5% at mid-July 2025 exchange rates. The Company now expects its full-year non-GAAP effective income tax rate to be between 15.0% and 16.0%. The Company now expects its full-year non-GAAP EPS to be between $8.87 and $8.97, including a revised negative impact of foreign exchange of approximately $0.15 per share. This revised non-GAAP EPS range continues to reflect the impacts of a one-time charge of $200 million (recorded in the second quarter of 2025) for an upfront payment made in connection with the closing of a license agreement with Hengrui Pharma and the one-time charge of $300 million (to be recorded in the third quarter of 2025) related to a payment to LaNova for the completion of the technology transfer for MK-2010, which will impact EPS by approximately $0.16 in the aggregate. In 2024, non-GAAP EPS of $7.65 was negatively impacted by a net charge of $1.28 per share related to certain asset acquisitions, licensing agreements and collaborations. The financial outlook does not include the anticipated impact of the announced acquisition of Verona Pharma. Consistent with past practice, the financial outlook does not assume additional significant potential business development transactions. The $200 million of costs previously included in the Company’s financial outlook related to the impact of tariffs is unchanged pending the outcome of additional potential government actions. Earnings Conference Call Investors, journalists and the general public may access a live audio webcast of the call on Tuesday, July 29, at 9 a.m. ET via this weblink. A replay of the webcast, along with the sales and earnings news release, supplemental financial disclosures and slides highlighting the results, will be available on the Company’s website. All participants may join the call by dialing (800) 369-3351 (U.S. and Canada Toll-Free) or (517) 308-9448 and using the access code 9818590. About Our Company At Merck & Co., Inc., Rahway, N.J., USA, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “Company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the Company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the Company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the Company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the Company’s Annual Report on Form 10-K for the year ended December 31, 2024 and the Company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov). Appendix Generic product names are provided below. Pharmaceutical BRIDION (sugammadex) CAPVAXIVE (Pneumococcal 21-valent Conjugate Vaccine) ENFLONSIA (clesrovimab-cfor) GARDASIL (Human Papillomavirus Quadrivalent [Types 6, 11, 16 and 18] Vaccine, Recombinant) GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) JANUMET (sitagliptin and metformin HCl) JANUVIA (sitagliptin) KEYTRUDA (pembrolizumab) Lenvima (lenvatinib) Lynparza (olaparib) M-M-R II (Measles, Mumps and Rubella Virus Vaccine Live) PREVYMIS (letermovir) PROQUAD (Measles, Mumps, Rubella and Varicella Virus Vaccine Live) SIMPONI (golimumab) VARIVAX (Varicella Virus Vaccine Live) VAXNEUVANCE (Pneumococcal 15-valent Conjugate Vaccine) WELIREG (belzutifan) WINREVAIR (sotatercept-csrk) Animal Health BRAVECTO (fluralaner) BRAVECTO QUANTUM (fluralaner for extended-release injectable suspension) NUMELVI (atinvicitinib) 1 All trademarks are property of their respective owners. 2 Net income attributable to the Company. 3 The Company is providing certain 2025 and 2024 non-GAAP information that excludes certain items because of the nature of these items and the impact they have on the analysis of underlying business performance and trends. Management believes that providing this information enhances investors’ understanding of the Company’s results because management uses non-GAAP results to assess performance. Management uses non-GAAP measures internally for planning and forecasting purposes and to measure the performance of the Company along with other metrics. In addition, annual employee compensation, including senior management’s compensation, is derived in part using a non-GAAP pretax income metric. This information should be considered in addition to, but not as a substitute for or superior to, information prepared in accordance with GAAP. For a description of the non-GAAP adjustments, see Table 2a attached to this release. 4 Reflects expenses related to business combinations, including the amortization of intangible assets, intangible asset impairment charges, and expense or income related to changes in the estimated fair value measurement of liabilities for contingent consideration. Also includes integration, transaction and certain other costs associated with acquisitions and divestitures, as well as amortization of intangible assets related to collaborations and licensing arrangements. 5 Includes the estimated tax impacts on the reconciling items based on applying the statutory rate of the originating territory of the non-GAAP adjustments for both periods presented. Amount in the second quarter of 2025 also includes a $146 million benefit primarily resulting from favorable audit adjustments. Amount in the second quarter of 2024 also includes a $259 million benefit due to a reduction in reserves for unrecognized income tax benefits resulting from the expiration of the statute of limitations for assessments related to the 2019 federal tax return year. GAAP % Change GAAP % Change 2Q25 2Q24 June YTD 2025 June YTD 2024 $ 15,806 $ 16,112 -2% $ 31,335 $ 31,887 -2% 3,557 3,745 -5% 6,976 7,285 -4% 2,649 2,739 -3% 5,202 5,221 0% 4,048 3,500 16% 7,669 7,492 2% 560 80 * 629 202 * (7 ) 42 * (43 ) 12 * 4,999 6,006 -17% 10,902 11,675 -7% 571 545 1,388 1,447 4,428 5,461 -19% 9,514 10,228 -7% 1 6 8 11 $ 4,427 $ 5,455 -19% $ 9,506 $ 10,217 -7% $ 1.76 $ 2.14 -18% $ 3.77 $ 4.02 -6% 2,513 2,544 2,522 2,544 11.4 % 9.1 % 12.7 % 12.4 % $ 3,557 576 165 741 $ 2,816 2,649 15 1 16 2,633 4,048 3 53 56 3,992 560 560 560 – (7 ) (61 ) (61 ) 54 4,999 (594 ) (779 ) 61 (1,312 ) 6,311 571 (102 ) (3) (139 ) (3) 14 (3) (146 ) (4) (373 ) 944 4,428 (492 ) (640 ) 47 146 (939 ) 5,367 4,427 (492 ) (640 ) 47 146 (939 ) 5,366 $ 1.76 (0.20 ) (0.25 ) 0.02 0.06 (0.37 ) $ 2.13 11.4 % 15.0 % $ 6,976 1,196 201 1,397 $ 5,579 5,202 38 1 39 5,163 7,669 10 53 63 7,606 629 629 629 – (43 ) (3 ) (168 ) (171 ) 128 10,902 (1,241 ) (884 ) 168 (1,957 ) 12,859 1,388 (219 ) (3) (157 ) (3) 36 (3) (146 ) (4) (486 ) 1,874 9,514 (1,022 ) (727 ) 132 146 (1,471 ) 10,985 9,506 (1,022 ) (727 ) 132 146 (1,471 ) 10,977 $ 3.77 (0.40 ) (0.29 ) 0.05 0.06 (0.58 ) $ 4.35 12.7 % 14.6 % 2025 2024 2Q June YTD 1Q 2Q June YTD 1Q 2Q June YTD 3Q 4Q Full Year Nom % Ex-Exch % Nom % Ex-Exch % $15,529 $15,806 $31,335 $15,775 $16,112 $31,887 $16,657 $15,624 $64,168 -2 -2 -2 0 13,638 14,050 27,688 14,006 14,408 28,415 14,943 14,042 57,400 -2 -3 -3 -2 7,205 7,956 15,161 6,947 7,270 14,217 7,429 7,836 29,482 9 9 7 8 312 370 682 292 317 609 337 365 1,311 17 15 12 12 258 265 523 255 249 504 251 255 1,010 6 5 4 4 137 162 300 85 126 211 139 160 509 29 29 42 43 119 107 226 71 90 161 100 110 371 19 19 40 40 1,327 1,126 2,453 2,249 2,478 4,727 2,306 1,550 8,583 -55 -55 -48 -48 539 609 1,148 570 617 1,187 703 594 2,485 -1 -2 -3 -3 230 229 459 219 189 408 239 161 808 21 20 13 13 228 121 349 216 163 379 193 139 711 -26 -26 -8 -7 107 129 236 47 50 97 - - - - 41 38 79 61 59 120 68 74 263 -36 -37 -35 -33 441 461 902 440 455 895 420 449 1,764 1 1 1 1 208 228 436 174 188 362 208 215 785 21 20 20 21 83 96 179 73 92 165 96 79 340 5 5 8 9 70 74 145 56 62 118 64 70 252 21 21 23 24 280 336 615 70 70 149 200 419 106 123 229 98 106 203 102 109 415 16 16 12 12 68 80 147 70 72 142 72 73 287 10 6 4 4 102 83 185 350 110 460 383 121 964 -25 -27 -60 -59 90 86 176 111 89 200 102 92 394 -3 -4 -12 -11 67 83 150 56 60 116 65 69 249 40 35 30 30 45 41 86 42 39 81 42 40 163 5 4 6 6 50 40 90 46 53 99 78 45 222 -24 -26 -9 -8 184 172 356 189 543 -100 -100 -100 -100 39 35 74 41 114 -100 -100 -100 -100 549 372 921 419 405 824 278 232 1,334 -8 -8 12 13 247 251 498 251 224 475 204 255 935 12 14 5 8 729 584 1,313 632 618 1,252 638 699 2,590 -6 -7 5 6 1,588 1,646 3,234 1,511 1,482 2,993 1,487 1,397 5,877 11 11 8 11 924 961 1,885 850 837 1,686 886 889 3,462 15 16 12 16 664 685 1,349 661 645 1,307 601 508 2,415 6 6 3 4 303 110 413 258 222 479 227 185 891 -50 -3 -14 7 Media Contacts: Michael Levey michael.levey@msd.com Johanna Herrmann johanna.herrmann@msd.com Investor Contacts: Peter Dannenbaum (732) 594-1579 Steven Graziano (732) 594-1583

Phase 3Clinical ResultDrug ApprovalAcquisitionFinancial Statement

02 Jun 2025

·www.fiercebiotech.com

ASCO’s bubble of hope: Execs focus on ‘rewriting textbooks’ in cancer care at conference

“I think it is a little bit of a nice bubble to be in at the moment, given all that\'s going on in the world,” Takeda\'s Teresa Bitetti said.\n The first half of this year has been riddled with market volatility and geopolitical tension. But 2025’s American Society of Clinical Oncology conference largely isn’t reflecting that turmoil.In fact, despite the chill in the air, the Chicago-based five-day meeting has felt quite the opposite. Though ASCO\'s CEO Clifford Hudis, M.D., kicked off the event with a warning about the devastating impact President Donald Trump\'s massive proposed budget cuts would have on the National Institutes of Health\'s National Cancer Institute, most attendees focused in on the potential that current pipeline programs could bring to Americans with cancer.“In a fairly tumultuous world, where we just see concerns on funding and concerns on following the science, and then you come into a venue like this—it is energizing when you see the cutting-edge science and how smart some of these advancements are,” Teresa Bitetti, president of Takeda’s global oncology business unit, told Fierce Biotech at the conference. “I think it is a little bit of a nice bubble to be in at the moment, given all that\'s going on in the world,” Bitetti added.Specific to Takeda, Bitetti said the newly shared phase 3 data for the pharma’s Protagonist Therapeutics-partnered asset designed to treat a rare chronic blood disorder was also fueling her excitement.The injectable hepcidin mimetic, called rusfertide, already met the hematology trial’s main endpoint, demonstrating a 76.9% clinical response when paired with standard of care compared to a 32.9% response for those receiving standard of care alone. That finding, which was announced in March, is now supplemented by additional findings, including details on key secondary endpoints, all of which hit their target. The late-stage trial enrolled patients with polycythemia vera (PV), a disease that increases the risk of life-threatening cardiovascular and thrombotic events, and therefore boosts the chances of requiring the regular removal of blood via phlebotomy in order to manage hematocrit levels.However, only 27% of patients in the investigational treatment arm required phlebotomy over the duration of 32 weeks, compared to 78% of patients who received placebo plus the current standard of care.“If I had had this years ago when I was practicing, I think I would have just been in tears with joy,” P.K. Morrow, M.D., head of Takeda’s oncology therapeutic area unit, told Fierce. The company is now on track to submit an approval request to the FDA in the second half of Takeda\'s fiscal year, which ends March 31, 2026.“That\'s why I do love my job, it\'s not often in your career when you can bring forward a transformative medicine, and we\'re doing that,” Bitetti added. “That, to me, is super exciting and very fulfilling.” The conference’s homebase, a sprawling convention center called McCormick Place, appears busy as ever. Fears that recent travel advisories cautioning international visitors from entering the U.S. would impact attendance seem not to have deterred global oncology leaders. A preliminary estimate from ASCO said international on-site registrations were on pace with last year, as of the second day of the conference.For Merck & Co.’s Marjorie Green, M.D., the conference remains a place to push forward with innovative cancer treatments.“Everyone is very happy with Keytruda, and we are too, but we know we can do better,” Merck’s senior vice president and head of oncology clinical development told Fierce. She cited Merck’s investigational KRAS G12C inhibitor, known as MK-1084, which the company is studying in a recently launched phase 3 for metastatic non-small cell lung cancer (NSCLC), plus a pivotal late-stage study slated to start next month in advanced colorectal cancer.In the NSCLC trial, the KRAS G12C inhibitor is being administered in combination with the company’s blockbuster PD-1 inhibitor Keytruda. The investigational duo will be compared against the standard of care in first-line metastatic nonsquamous NSCLC, which is Keytruda combined with pemetrexed and carboplatin.“So, we’re trying to get rid of chemotherapy,” Green explained. “Rewriting textbooks, that’s what we’re going to do.”And though, in the words of Fierce Pharma’s Angus Liu, this ASCO may not have “a lot of drama in the data” occurring, any chance to learn from other thought leaders and trials being presented is a golden one.“Even if a study is a negative study, you\'ve learned something important, and we build upon whatever that is,” Green said. “You\'ve answered an important question and are advancing science. We always want to advance progress for patients.”“The promise of ASCO is exciting,” she said.

Phase 3ASCOAccelerated ApprovalClinical Result

02 Jun 2025

·www.pharmaceutical-technology.com

ASCO25: MSD’s KRAS G12C drug shows early promise in Phase I

MSD investigated the KRAS G12C inhibitor in patients with solid tumours, including advanced colorectal cancer and non-small cell lung cancer. Image credit: Shutterstock / Atmosphere1. MSD’s investigational KRAS G12C inhibitor has shown signs of anti-tumour activity when used both alone and in combination with other oncology drugs. Announcing the data at the American Society of Clinical Oncology (ASCO) meeting 2025, being held from 30 May to 3 June in Chicago, MSD said that MK-1084 was also safe and tolerable in patients with solid tumours, including advanced colorectal cancer (CRC) and non-small cell lung cancer (NSCLC), in the Phase I KANDLELIT-001 trial (NCT05067283). In patients with CRC, there was a 38% confirmed overall response rate (ORR) in the monotherapy arm. When used in combination with Erbitux (cetuximab), there was a 46% confirmed ORR, and when used with both Erbitux and mFOLFOX6(oxaliplatin and leucovorin plus 5-fluorouracil), the confirmed ORR was 38%. Investigators also reported 43% unconfirmed ORR with MK-1084 alone, 56% in combination with Erbitux and 66% in combination with Erbitux and mFOLFOX6. In patients with NSCLC, there was an ORR of 38% in the monotherapy arm, 77% when it was used in combination with Keytruda (pembrolizumab), and 53% when used with Keytruda and chemotherapy (carboplatin and pemetrexed). In all arms, MSD states that MK-1084 had a manageable safety profile. Treatment-related adverse events (AEs) occurred in 58% of patients in the MK-1084 monotherapy arm; 94% of patients in the MK-1084 and Keytruda arm;, 93% of patients in the MK-1084, Keytruda and chemotherapy arm; 95% of patients in the MK-1084 and Erbitux arm; and 97% of patients in the MK-1084 with Erbitux and mFOLFOX6 arm. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence MSD Research Laboratories SVP and oncology, global clinical development Dr Marjorie Green said: “We are encouraged by the promising early data from the KANDLELIT-001 study and look forward to further researching the potential for MK-1084, as monotherapy or in combinations, including with Keytruda in certain settings in patients with KRAS mutations, which are among the most prevalent mutations in cancer.” MSD is also investigating the KRAS G12C in several Phase III trials, including the Phase III KANDLELIT-012 study in patients with unresectable or metastatic CRC with KRAS G12C-mutated tumours and the Phase III KANDLELIT-004 study in patients with NSCLC with KRAS G12C-mutated tumours that express PD-L1 (NCT06345729). ASCO updates MSD also reported data from a Phase II/III study of zilovertamab vedotin as a combination therapy in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study achieved a 56.3% ORR. Other major pharmaceutical companies have also revealed data around the ASCO 2025 conference. Pfizer announced data from its Phase III BREAKWATER study of Braftovi (encorafenib) in combination with Erbitux and mFOLFOX6. Merck KGaA also highlighted success in two studies, a Phase III trial of its CSF-1R inhibitor pimicotinib in tenosynovial giant cell tumour (TGCT) patients and a Phase I study of M9140, a CEACAM5-targeting antibody-drug conjugate (ADC), in patients with metastatic CRC . Pharmaceutical Technology Excellence Awards - Have you nominated? Nominations are now open for the prestigious Pharmaceutical Technology Excellence Awards - one of the industry's most recognised programmes celebrating innovation, leadership, and impact . This is your chance to showcase your achievements, highlight industry advancements , and gain global recognition . Don't miss the opportunity to be honoured among the best - submit your nomination today! Nominate Now

Phase 1ASCOClinical ResultPhase 3ADC

100 Deals associated with MK-1084

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Colonic Cancer	Phase 3	Israel	Merck Sharp & Dohme LLC	16 Jul 2025
Colonic Cancer	Phase 3	Taiwan Province	Merck Sharp & Dohme LLC	16 Jul 2025
KRAS G12C mutant Colorectal Cancer	Phase 3	Israel	Merck Sharp & Dohme LLC	16 Jul 2025
KRAS G12C mutant Colorectal Cancer	Phase 3	Taiwan Province	Merck Sharp & Dohme LLC	16 Jul 2025
Rectal Adenocarcinoma	Phase 3	Israel	Merck Sharp & Dohme LLC	16 Jul 2025
Rectal Adenocarcinoma	Phase 3	Taiwan Province	Merck Sharp & Dohme LLC	16 Jul 2025
KRAS G12C mutant Non-small Cell Lung Cancer	Phase 3	United States	MSD R&D (China) Co. Ltd.	24 May 2024
KRAS G12C mutant Non-small Cell Lung Cancer	Phase 3	United States	Merck Sharp & Dohme LLC	24 May 2024
KRAS G12C mutant Non-small Cell Lung Cancer	Phase 3	China	Merck Sharp & Dohme LLC	24 May 2024
KRAS G12C mutant Non-small Cell Lung Cancer	Phase 3	Japan	Merck Sharp & Dohme LLC	24 May 2024

Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05067283 (KANDLELIT-001, ASCO2025 \| NEWS) Manual	Phase 1	Advanced Malignant Solid Neoplasm \| KRAS G12C mutant Colorectal Cancer KRAS G12C	153	MK-1084 monotherapy (any advanced solid tumor and ≥1 prior systemic therapy + arms 1 and 3)	sufdegecil(mohrgupoop) = xznfuuhvqb ypqtvcmyhj (wxofsuojqm ) View more	Positive	30 May 2025
				MK-1084 + cetuximab (advanced CRC and 1-2 prior systemic therapies + arm 5)	sufdegecil(mohrgupoop) = zxfgyiokos ypqtvcmyhj (wxofsuojqm ) View more
NCT05067283 (KANDLELIT-001, ASCO2025 \| NEWS) Manual	Phase 1	KRAS G12C mutant Non-small Cell Lung Cancer \| KRAS G12C mutation Solid Tumors KRAS G12C	183	MK-1084 monotherapy (arms 1 and 3 + any advanced solid tumor and ≥1 prior systemic therapy)	qfmooqhgfw(pxsuuecgcc) = eyvwvqxirv ymqvdasncy (bczwgwrtkv ) View more	Positive	30 May 2025
				MK-1084 + pembrolizumab (previously untreated mNSCLC and PD-L1 TPS ≥1% + arm 2)	qfmooqhgfw(pxsuuecgcc) = lzelymznax ymqvdasncy (bczwgwrtkv ) View more
NCT05067283 (phase I study, ESMO_TAT2024) Manual	Phase 1	KRAS G12C mutation Solid Tumors \| KRAS G12C mutant Non-small Cell Lung Cancer First line KRAS G12C	78	MK-1084	oytxvntmbd(fexrxgthdg) = uejzkztagk zpepsofzok (wyqxedjain ) View more	Positive	26 Feb 2024
				MK-1084 + pembrolizumab	oytxvntmbd(fexrxgthdg) = nwtzqznnrz zpepsofzok (wyqxedjain ) View more
NCT05067283 (MK-1084-001 \| 1084-001, ESMO 12023 \| ESMO 22023) Manual	Phase 1	Solid tumor \| Non-Small Cell Lung Cancer KRAS G12C mutation	58	MK-1084	xthluxelpo(zqaybxjutf) = hrmdmgagqk ftvsvddiuh (lybfmwsedf ) View more	Positive	23 Oct 2023
				MK-1084 + pembrolizumab	xthluxelpo(zqaybxjutf) = fybytzavma ftvsvddiuh (lybfmwsedf ) View more

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