Request Demo
Last update 28 Oct 2026
Calderasib
Last update 28 Oct 2026
Overview
Basic Info
Drug Type Small molecule drug |
Synonyms MK 1084, MK-1084 |
Target |
Action inhibitors |
Mechanism KRAS G12C inhibitors(GTPase KRas G12C inhibitors) |
Therapeutic Areas |
Inactive Indication- |
Originator Organization |
Active Organization |
Inactive Organization- |
License Organization- |
Drug Highest PhasePhase 3 |
First Approval Date- |
RegulationBreakthrough Therapy (China) |
Login to view timeline
Structure/Sequence
Molecular FormulaC32H31ClF2N6O4 |
InChIKeyBBIVCWWQPMOKAC-UHFFFAOYSA-N |
CAS Registry2641216-67-1 |
Related
19
Clinical Trials associated with CalderasibNCT07554339
A Phase 3, Randomized, Double-blind, Placebo- and Active-Comparator-Controlled Study of MK-1084 Plus Durvalumab Versus Placebo Plus Durvalumab in Participants With Locally Advanced, Unresected KRAS G12C-Mutant Non-Small Cell Lung Cancer Without Disease Progression Following Definitive Platinum-Based Chemoradiotherapy (KANDLELIT-015)
Researchers are looking for new ways to treat locally advanced non-small cell lung cancer (NSCLC) that is unresected and has a gene mutation called KRAS G12C. Researchers want to learn if calderasib (MK-1084) can be given with durvalumab, an immunotherapy, to treat NSCLC after chemotherapy and radiation therapy.
The goal of this trial is to learn if participants who receive calderasib and durvalumab live longer without the cancer growing or spreading compared to participants who receive placebo and durvalumab.
The goal of this trial is to learn if participants who receive calderasib and durvalumab live longer without the cancer growing or spreading compared to participants who receive placebo and durvalumab.
Start Date18 Jun 2026 |
Sponsor / Collaborator |
ChiCTR2600124257
KEYMAKER-U01 Substudy 01F: A Phase 1b/2 Umbrella Study With Rolling Arms of Investigational Agents for Previously Treated Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations
Start Date15 May 2026 |
Sponsor / Collaborator- |
NCT07286149
KEYMAKER-U01 Substudy 01F: A Phase 1b/2 Umbrella Study With Rolling Arms of Investigational Agents for Previously Treated Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations
Researchers want to learn if MK-1084, the study medicine, can treat advanced or metastatic non-squamous NSCLC. MK-1084 is a targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread. The goals of this study are to learn:
* About the safety of MK-1084 and if people tolerate it when taken with other treatments
* How many people have the cancer respond (get smaller or go away) to the treatments
* About the safety of MK-1084 and if people tolerate it when taken with other treatments
* How many people have the cancer respond (get smaller or go away) to the treatments
Start Date30 Apr 2026 |
Sponsor / Collaborator |
100 Clinical Results associated with Calderasib
Login to view more data
100 Translational Medicine associated with Calderasib
Login to view more data
100 Patents (Medical) associated with Calderasib
Login to view more data
7
Literatures (Medical) associated with Calderasib28 May 2026·CANCER INVESTIGATION
A Systematic Review of the Efficacy of KRAS p.G12C Inhibitors in Metastatic Colorectal Cancer: The Current State of Science
Review
Author: Baytar, Doga Kahramangil ; Boby, Jeffrey Mathew ; Benny, Jame Mathew ; Peniche, Paola Zinser ; Sahin, Ibrahim Halil ; Ilerhunmwuwa, Nosakhare
BACKGROUND:
KRAS p.G12C (c.34G > T) inhibitors have been reported to have varying survival outcomes in CRC patients across studies. Hence, our review aimed to provide a comprehensive understanding of the efficacy and safety of these agents among the CRC population.
METHODS:
Major databases, including but not limited to PubMed and Ovid, were searched for original clinical trials assessing the efficacy or safety of KRAS p.G12C (c.34G > T) inhibitors in CRC patients through May 2025. Studies with non-G12C KRAS-mutated populations were excluded. Data on patient demographics and various variables, including but not limited to OS, PFS, and TRAE incidence, were extracted from included studies.
RESULTS:
Our systematic review analyzed 18 trials and 1011 patients. Adagrasib monotherapy yielded a median PFS of 4.4-5.6 months, an OS of 10-19.8 months, and an ORR of 19-23%, while its combination with cetuximab reported a PFS of 6.9 months, an OS of 13.4-15.9 months and an ORR of 34-46%. Sotorasib monotherapy (960 mg) reported a PFS of 4 months, an OS of 10.6 months, and an ORR of 9.7. When combined with panitumumab, 960 mg sotorasib demonstrated better results with a PFS of 5.6-5.7 months, OS of 15.2 months and an ORR of 12.5-30%. Similarly, divarasib monotherapy led to a PFS of 5.6-6.9 months and an ORR of 20%, while its combination with cetuximab resulted in a PFS of 8.1 months and an ORR of 62.5%. Combination therapy of olomorasib and MK-1084, which are new-generation KRAS p.G12C (c.34G > T) inhibitors, with cetuximab also demonstrated highly promising efficacy with ORR of 38-44% and 50%, respectively. Olomorasib with cetuximab also showed a PFS of 6.6-7.5 months. Nausea, vomiting, diarrhea, rash, and increased AST/ALT were the most common TRAEs.
CONCLUSIONS:
Initial results of KRAS-G12C inhibitors appear highly promising when they are combined with anti-EGFR therapy compared to historical therapeutic agents indicated for patients with chemotherapy-refractory CRC. Encouraging benefits warrant frontline trials with these novel therapeutics.
23 Apr 2026·JOURNAL OF MEDICINAL CHEMISTRY
From KRAS
G12D
to Pan-KRAS Inhibitors─A Journey Enabled by Synthetic Innovation and Structure-Based Drug Design
Article
Author: Schopf, Patrick ; Lacey, Brian M. ; Day, Philip J. ; O’Reilly, Marc ; Sagara, Takeshi ; Duggal, Ruchia ; Sloman, David L. ; Edelstein, Emma ; Lyons, Thomas W. ; Hoover, Andrew ; Swaminathan, Uma ; Otte, Ryan D. ; Chessari, Gianni ; Stoeck, Alexander ; Shibata, Kazuaki ; Palani, Anandan ; Ye, Yingchun ; Bennett, D. Jonathan ; Solban, Nicolas ; Kobayakawa, Yu ; Su, Dan ; Han, Yongxin ; Miller, Richard ; Ma, Xiaoshen ; Venkataraman, Sriraman ; Howard, Steven ; Gathiaka, Symon ; Henderson, Timothy J. ; Sather, Aaron ; Shikata, Yuki ; Rees, David C. ; Munsell, Erik V. ; Oshima, Tsuyoshi ; Kawamura, Shuhei ; Mizuarai, Shinji ; Mansueto, My S.
KRAS, a significant oncology target, has been challenging to develop drugs for until recent discoveries of KRASG12C mutant-specific covalent inhibitors, including MK-1084. This article describes efforts toward the discovery of KRASG12D mutant-specific inhibitors and how synthetic innovations and structure-based drug design were utilized to facilitate the discovery of pan-KRAS inhibitors.
23 Jan 2026·ORGANIC LETTERS
Asymmetric Synthesis of KRAS G12C Inhibitor MK-1084 via a Crystallization-Induced Diastereomer Transformation (CIDT)
Article
Author: Kwan, Eugene E. ; Johnson, Heather C. ; Kong, Jongrock ; Wen, Xin ; Xu, Jing ; Nawrat, Christopher C. ; Yuan, Yongpeng ; Chen, Yonggang ; Shang, Gao ; He, Cyndi Qixin ; Belyk, Kevin M. ; Wan, Baoqiang ; Xiao, Kai-Jiong ; Hughes, Jonathan M. E. ; Song, Zhiguo J. ; Song, Zhiyan ; Li, Hongming ; Maddess, Matthew ; Zhang, Jin ; Sather, Aaron C. ; Yin, Jingjun ; Tan, Lushi ; Liu, Guiquan ; Fan, Chao ; Lam, Yu-hong
MK-1084 is a potent KRAS G12 inhibitor characterized by a complex macrocyclic ring system incorporating two atropisomeric axes from a restricted rotation around both C-C and N-C bonds. Herein, we report an efficient synthetic approach to manufacture MK-1084 to enable clinical trials. By leveraging the in-depth understanding of the inherent properties of axial chirality, we discovered and developed a one-pot crystallization-induced diastereomer transformation (CIDT)/carbonylation process to establish the unique and challenging macrocyclic core with double axial chiral centers from a racemic advanced precursor and readily available raw materials.
33
News (Medical) associated with Calderasib27 Oct 2026
Every ESMO conference is eventful, but the drama kicked into gear earlier than expected this year when the eagerly anticipated phase 3 data for Moderna and Merck & Co.’s cancer vaccine were leaked two days before the Presidential Symposium.
Shweta Jain, vice president of global clinical development and oncology clinical research at Merck, acknowledged to Fierce in an interview that the leak was “unfortunate,” but explained that the Big Pharma and its partner had stuck to their plan on how to present the data on Saturday.
Going public with the headline data earlier than expected certainly didn’t deter delegates from queuing up for the Saturday symposium. As with previous ESMO show-stoppers, interest was so high that latecomers were reduced to standing around the sidelines of the cavernous Alicante Auditorium.
But it’s easy to assume that the slightly muted atmosphere during the presentation would have been more electric if the audience had been in genuine suspense about the data being unveiled.
Jain may have been resigned to the leak and wanted to focus attention on the trial's “convincing data,” but the ESMO organizers weren’t quite as relaxed. For this conference, Fierce—along with all journalists—was barred from entering either of the exhibition halls under a new policy preventing access to non-healthcare prescribers.
ESMO’s press office told Fierce they “understand your disappointment … and appreciate the frustration this has caused.” But they laid the blame on European legislation governing the promotion of medical products.
Biopharma executives who spoke to Fierce under the condition of anonymity speculated that this hard-line approach was, in fact, a knee-jerk reaction to the negative publicity surrounding the vaccine data leak.
For Merck’s Jain, the intismeran autogene readout was just the most high-profile announcement in a packed ESMO package from the Big Pharma that featured around seven oral presentations alongside “many, many, many abstracts and posters.”
That included two other presidential symposia to showcase Chinese phase 3 data for the Kelun-Biotech-partnered antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT), as well as the potential for Keytruda to treat patients with a type of endometrial cancer.
Merck also reminded everyone that it has a contender in the hotly contested KRAS G12C inhibitor space by offering early data on how calderasib performed against solid tumors.
“I would say, put together, it just generally shows that we are working towards a more diverse portfolio,” Jain concluded.
At last year’s conference in Berlin , the general consensus was that next-gen ADCs were the stars of the show. But during Fierce’s conversations with senior executives from over 10 Big Pharmas and biotechs, as well as doctors and other attendees milling around the walkways of the sun-dappled IFEMA venue in outer Madrid, there was an altogether different vibe.
In fact, the overarching view was that this year’s theme was: there was no theme.
“I don't see a theme, right?” Incyte’s Global Head of R&D, Pablo Cagnoni, M.D., told Fierce in an impromptu interview in the empty ESMO press conference room.
With Incyte keen to pitch its KRAS G12D inhibitor INCB161734 as the only real rival to Revolution Medicine’s Rasonque follow-up zoldonrasib, Cagnoni acknowledged his focus at the conference had been on “a lot of KRAS stuff happening.”
Despite this tunnel vision, Cagnoni could still see the bigger picture.
“I walked into a couple of presentations randomly, and they were talking about applications of AI from anything from diagnosis to patient care-directed applications,” he said. “So I think that’s a big theme.”
“I think it’s impossible at this ESMO to not talk about the Moderna [cancer] vaccine,” he continued. “There’s strong passions on both sides—I happen to think the data are really good.”
“And the third point I would make is I was struck by the quality of the ovarian cancer readout from Genmab on Friday,” said Cagnoni, referencing the Danish biopharma’s phase 3 win for its Elahere rival Rina-S.
“A first analysis of a study showed survival hazard ratio 0.43,” he explained. “I think that is a really important data set for patients with ovarian cancer.”
Stefan Frings, M.D., Ph.D., deputy chief medical officer at Roche Pharma, had a similar take.
“I would expect that there’s not a single theme, but rather many attractive modalities,” he summarized of the current state of the oncology R&D space.
“We tailor … the target to the modality,” Frings explained. “Sometimes it can be an ADC, sometimes immunotherapy.”
“Sometimes combination targeted molecules like divarasib are still very attractive,” he said, namechecking Roche’s own KRAS G12C inhibitor that aced Amgen’s Lumakras and Bristol Myers Squibb’s Krazati in a phase 3 non-small cell lung cancer study.
“It showcases here that we are making progress in treating cancer,” he concluded.
For the duration of the conference, Roche set up shop in an elegant hotel a couple of miles away from IFEMA. The Swiss pharma weren’t the only ones to seek some calm away from the bustle of the ESMO crowds.
Next, Fierce headed to a Novotel a stone’s throw from the venue to catch up with Yusri Elsayed, M.D., Ph.D., global oncology therapeutic area head at Johnson & Johnson Innovation, to get his take.
J&J had some exciting early-stage data from the regulated induced proximity targeting chimera (RIPTAC) platform acquired in its Halda Therapeutics buyout last year. But Elsayed was similarly open-minded about the most exciting mechanisms on display at this year’s ESMO.
“We are very excited about the RIPTAC, of course,” he said. “But we are also very excited about ways of trying to reach patients, minimizing toxicities and increasing efficacy.”
“For example, we are working now on degrader-antibody conjugates ,” he said, alluding to a platform J&J picked up in its Firefly Bio acquisition in June. “You don't hear about it a lot, but definitely for next ESMO.”
Elsayed and his team were also “excited to hear about” Merck and Moderna’s vaccine success, he pointed out.
As to the reduced emphasis on ADCs this year, “I don't think that’s a bad thing,” he said.
“The emergence of new mechanisms of action, I think, is very exciting.”
That’s not to say that ADCs were kept a low profile at this year’s ESMO. As well as Merck's sac-TMT, GSK unveiled fresh phase 1 data from its Hansoh-partnered B7-H4-directed mo-rez, while AstraZeneca insisted to Fierce that the mixed phase 3 gastric cancer data for its Claudin18.2-targeting sono-ve will be enough to win over regulators.
Takeda used ESMO to lift the lid on its own late-stage success for a CLDN18.2 ADC, called arcotatug tavatecan. As far as P.K. Morrow, M.D., head of Takeda’s oncology therapeutic area unit, was concerned, the modality still has plenty to offer.
“What you saw here—not just with this, but other data across ESMO—is how do we continue to optimize the tolerability profile so we can deliver the degree of efficacy to patients,” she told Fierce.
“So ADCs really are here to stay,” she added.
The most exciting areas of biopharma R&D is among the hot topics being discussed at Fierce Biotech's high-impact event in London next month. Find out more information and register by clicking on the banner below:
Phase 3VaccineClinical ResultImmunotherapyADC
13 Oct 2026
INTerpath-001 data to be presented in Presidential Symposium, featuring the first Phase 3 results for investigational intismeran autogene plus KEYTRUDA
®
(pembrolizumab), demonstrating improvements in recurrence-free survival and distant metastasis-free survival versus KEYTRUDA alone in patients with completely resected stage IIB-IV melanoma in the adjuvant setting
Investigational sacituzumab tirumotecan (sac-TMT) data from TroFuse-005, the first and only Phase 3 trial of a TROP2-directed antibody-drug conjugate to improve overall survival and progression-free survival in certain patients with advanced or recurrent endometrial cancer, will be presented in a Presidential Symposium
KEYNOTE-C93 data to be presented in Presidential Symposium suggesting important role of first-line KEYTRUDA monotherapy for certain patients with mismatch repair deficient (dMMR) advanced or recurrent endometrial cancer
RAHWAY, N.J.--(BUSINESS WIRE)--
$MRK
#MRK
--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that first-time results from three pivotal clinical trials will be presented during late-breaking Presidential Symposia at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain from Oct. 23-27. Additionally, more than 90 additional abstracts across more than 20 tumor types from the company’s pipeline and portfolio will be presented throughout the meeting.
“New data at ESMO, including three Presidential Symposia from three pivotal trials, reflect the strength and depth of Merck’s industry-leading oncology portfolio and pipeline,” said Dr. Marjorie Green, senior vice president and head of oncology global clinical development, Merck Research Laboratories. "We are proud to share Phase 3 data for the first time from intismeran and sac-TMT, alongside new research from our oncology portfolio, reflecting our commitment to advancing research across a range of cancer types."
Key data from Merck’s pipeline and portfolio to be presented:
First presentation of data from the pivotal Phase 3 INTerpath-001 trial evaluating intismeran autogene (intismeran; V940/mRNA-4157), a novel investigational mRNA-based individualized neoantigen therapy, in combination with KEYTRUDA
®
(pembrolizumab), Merck’s anti-PD-1 therapy, as adjuvant treatment for patients with completely resected stage IIB-IV melanoma, which will be featured in an ESMO Presidential Symposium (Presentation #LBA1, Proffered paper session: Presidential Symposium I).
1
First presentation of data from the pivotal Phase 3 TroFuse-005 trial evaluating sacituzumab tirumotecan (sac-TMT), an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate, for patients with advanced or recurrent endometrial cancer who have progressed after platinum-based chemotherapy and a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, which will be featured in an ESMO Presidential Symposium (Presentation #LBA11, Proffered paper session: Presidential Symposium III).
2,3
First presentation of data from the Phase 3 KEYNOTE-C93 trial evaluating KEYTRUDA monotherapy as a first-line treatment for patients with mismatch repair deficient (dMMR) advanced or recurrent endometrial cancer who had not previously received systemic chemotherapy or who experienced recurrence after receiving prior adjuvant therapy, which will be featured in an ESMO Presidential Symposium (Presentation #LBA12, Proffered paper session: Presidential Symposium III).
3
Data from Phase 3 OptiTROP studies evaluating sac-TMT in non-small cell lung cancer (NSCLC), including results from the OptiTROP-Lung06 study (Presentation #LBA66) in first-line PD-L1-negative advanced non-squamous NSCLC and final overall survival data from the OptiTROP-Lung04 study (Presentation #LBA67) in epidermal growth factor receptor (EGFR)-mutated NSCLC following progression on EGFR tyrosine kinase inhibitors (TKIs) (Proffered paper session 1: NSCLC, metastatic).
4
Final analysis results from the Phase 3 LITESPARK-011 study evaluating WELIREG
®
(belzutifan), Merck’s first-in-class, oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, in combination with LENVIMA
®
(lenvatinib), an orally available multiple receptor TKI discovered by Eisai, for patients with advanced renal cell carcinoma with a clear cell component following a PD-1 or PD-L1 inhibitor (Presentation #3587O, Proffered paper session 2: Genitourinary tumours, renal and urothelial).
5
Merck investor event
Merck will hold an Oncology Investor Event to coincide with the ESMO 2026 Congress on Monday, October 26, 7:30 p.m. CET/2:30 p.m. ET, during which senior management will provide an update on the company’s oncology strategy and program. The event will take place in Madrid, Spain, and will be accessible via webcast. Investors, analysts, members of the media and the general public are invited to listen to a webcast of the presentation via this
weblink
. All participants may join the call by dialing (800) 369-2154 (U.S. and Canada Toll-Free) or (517) 308-9422 and using the access code 8984239.
Details on presentations listed above and additional key presentations for Merck
Breast cancer
Final OS analysis of sacituzumab tirumotecan versus chemotherapy in previously treated locally recurrent or metastatic triple-negative breast cancer: Phase III OptiTROP-Breast01. M. Li.
4
Presentation #4639RO, Rapid oral session 2: Breast cancer, advanced stage
Results from KEYNOTE-B49: A Phase 3, randomized, double-blind study of pembrolizumab (pembro) vs placebo (pbo) plus chemotherapy (CT) in participants (pts) with HR+/HER2− advanced breast cancer (ABC). H. S. Rugo.
Presentation #LBA51, Proffered paper session 2: Breast cancer, early and advanced stage
Association between disease control and patient-reported functioning and quality of life in the ASCENT-04/KEYNOTE-D19 study. K. Kalinsky.
6
Presentation #4659P, Poster session: Triple negative breast cancer
Gastrointestinal cancers
Adjuvant intismeran autogene plus FOLFIRINOX in resectable pancreatic ductal adenocarcinoma: Results from a Phase I study. D. J. Pinato.
1
Presentation #3151P, Poster session: Pancreatic cancer
Genitourinary cancers
Final analysis of the Phase 3 LITESPARK-011 study: Belzutifan (bel) plus lenvatinib (len) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti-PD-(L)1 therapy. D. Y. Heng.
5
Presentation #3587O, Proffered paper session 2: Genitourinary tumours, renal and urothelial
Final protocol-prespecified analysis of the Phase 3 KEYNOTE-564 trial of adjuvant pembrolizumab versus placebo in clear cell renal cell carcinoma (ccRCC). T. K. Choueiri.
Presentation #3589RO, Rapid oral session 2: Genitourinary tumours, renal and urothelial
Enfortumab vedotin (EV) with or without pembrolizumab (P) as first-line (1L) treatment for cisplatin (cis)-ineligible locally advanced or metastatic urothelial carcinoma (la/mUC): Long-term follow-up analysis from EV-103 cohorts DE/A and K. J. P. Maroto Rey.
7
Presentation #4740RO, Rapid oral session 1: Genitourinary tumours, renal and urothelial
ctDNA analysis of the Phase 3 KEYNOTE-B15 trial: Neoadjuvant and adjuvant (neoadj-adj) enfortumab vedotin (EV) + pembrolizumab (pembro) for participants (pts) with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin. J. A. Chatzkel.
7
Presentation #4734O, Proffered paper session 1: Genitourinary tumour, renal and urothelial
Health-related quality of life (HRQoL) with neoadjuvant and adjuvant (neoadj-adj) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) eligible for cisplatin in the Phase 3 KEYNOTE-B15 study. A. Gomez de Liano Lista.
7
Presentation #4738RO, Rapid oral session 1: Genitourinary tumours, renal and urothelial
Perioperative pembrolizumab (pembro) or enfortumab vedotin (EV) plus pembro in pts with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: Ad hoc analysis from KEYNOTE-905. A. Ullén.
7
Presentation #4733O, Proffered paper session 1: Genitourinary tumour, renal and urothelial
Sacituzumab tirumotecan (sac-TMT) + pembrolizumab (pembro) for locally advanced or metastatic urothelial carcinoma (la/mUC): Results from a Phase 2 Study (2870-002/SKB264-II-06). X. Bian.
4
Presentation #4739RO, Rapid oral session 1: Genitourinary tumours, renal and urothelial
Updated results from the Phase 1b/2 KEYNOTE-365 cohort I: Pembrolizumab (pembro) + carboplatin and etoposide chemotherapy (chemo) or chemo alone for neuroendocrine prostate cancer (NEPC). G. von Amsberg.
Presentation #2217RO, Rapid oral session: Genitourinary tumours, prostate, penile and testis
Gynecologic cancers
Sacituzumab tirumotecan in previously treated advanced or recurrent endometrial cancer: Results from the Phase 3 TroFuse-005/ENGOT-en23/GOG-3095 study. D. Lorusso.
2,3
Presentation #LBA11, Proffered paper session: Presidential Symposium III
KEYNOTE-C93/GOG-3064/ENGOT-en15: Phase 3, randomized, open-label study of first-line (1L) pembrolizumab (pembro) vs carboplatin (C) + paclitaxel (P) in mismatch repair-deficient (dMMR) advanced or recurrent endometrial carcinoma (a/rEC). B. M. Slomovitz.
3
Presentation #LBA12, Proffered paper session: Presidential Symposium III
Raludotatug deruxtecan (R-DXd) + bevacizumab (bev) in participants (pts) with platinum-resistant recurrent ovarian cancer (PROC): Results for cohort B-1 of the Phase 1b/2 REJOICE-Ovarian02 study. A. Oaknin.
8
Presentation #1247RO, Rapid oral session 2: Gynaecological cancers
Raludotatug deruxtecan (R-DXd) in patients (pts) with platinum-resistant ovarian cancer (PROC): An updated analysis of efficacy and tolerability from the Ph 2 part of REJOICE-Ovarian01. K. Hasegawa.
8
Presentation #1331P, Poster session: Gynaecological cancers
NRG-GY020: Phase III randomized trial of radiation +/- MK-3475 (pembrolizumab) for newly diagnosed early-stage high intermediate risk (HIR) mismatch repair deficient (dMMR) endometrioid endometrial cancer. F. Backes.
9
Presentation #1239O, Proffered paper session: Gynaecological cancers
Sacituzumab tirumotecan (sac-TMT) + pembrolizumab (pembro) in post-platinum advanced mismatch repair proficient (pMMR) endometrial cancer (EC): Results from a Phase 2 study (2870-002/SKB264-II-06). L. Chen.
4
Presentation #1259P, Poster session: Gynaecological cancers
Head and neck cancer
Practical considerations for adopting perioperative pembrolizumab in locally advanced head and neck squamous cell carcinoma (LA HNSCC) in Europe: Insights from KEYNOTE-689. M. Oliva.
Presentation #1580P, Poster session: Head and neck cancer, excluding thyroid
Lung cancer
Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (P) versus chemotherapy (chemo) plus pembrolizumab (P) as first-line (1L) treatment for PD-L1 negative advanced non-squamous (nsq) NSCLC: Randomized Phase 3 OptiTROP-Lung06 study. C. Zhou.
4
Presentation #LBA66, Proffered paper session 1: NSCLC, metastatic
Final OS analysis of sacituzumab tirumotecan (sac-TMT) versus platinum-based chemotherapy in EGFR-mutated non-small cell lung cancer (NSCLC) after progression on EGFR-TKI: Phase III OptiTROP-Lung04 study. W.F. Fang.
4
Presentation #LBA67, Proffered paper session 1: NSCLC, metastatic
Calderasib (MK-1084), alone or in combination, for KRAS G12C-mutant metastatic non-small cell lung cancer (mNSCLC). M. A. N. Sendur.
10
Presentation #2680RO, Rapid oral session 2: NSCLC, metastatic
Final analysis of adjuvant pembrolizumab (pembro) in resected early-stage non–small-cell lung cancer (NSCLC): Phase 3 PEARLS/KEYNOTE-091 study. M. E. O’Brien.
Presentation #2511O, Proffered paper session: Non-metastatic NSCLC and other thoracic malignancies
Ifinatamab deruxtecan (I-DXd) in extensive-stage small cell lung cancer (ES-SCLC): IDeate-Lung01 updated results. M. Ahn.
8
Presentation #3842P, Poster session: SCLC
Melanoma
INTerpath-001: Phase 3 study of the mRNA-based individualized neoantigen therapy (INT) intismeran autogene (intismeran) plus pembrolizumab (pembro) vs pembro alone for adjuvant treatment of resected stage IIB-IV melanoma (MEL). G. V. Long.
1
Presentation #LBA1, Proffered paper session: Presidential Symposium I
STARBOARD Phase 3: A randomized, double-blind study of first-line (1L) encorafenib (enco), binimetinib (bini) and pembrolizumab (pembro) vs placebo (pbo) and pembro for unresectable locally advanced or metastatic BRAF V600-mutant melanoma. D. Schadendorf.
7
Presentation #2071O, Proffered paper session: Melanoma and other skin tumours
Physician perspectives on defining cure in early-stage melanoma. H. M. Shaw.
Presentation #2173eP, ePoster session: Melanoma
Patritumab deruxtecan (HER3-DXd) in melanoma after anti-PD-(L)1 therapy: Primary analysis from HERTHENA-PanTumor01. M. McKean.
8
Presentation #2073RO, Rapid oral session: Melanoma and other skin tumours
Multi-tumor
Final results of the TUXEDO-3 Phase II trial of patritumab deruxtecan (HER3-DXd) in active brain metastases (BMs) and leptomeningeal disease (LMD). M. Preusser.
8
Presentation #690O, Proffered paper session: CNS tumours
Calderasib monotherapy in various KRAS G12C-mutated advanced solid tumors: Results from the Phase 1 KANDLELIT-001 study. M Kwiatkowski.
10
Presentation #1039P, Poster session: Developmental therapeutics
1
In collaboration with Moderna
2
In collaboration with Kelun-Biotech
3
In collaboration with the European Network for Gynaecological Oncology Trial (ENGOT) groups and the GOG Foundation, Inc. (GOG)
4
Led by Kelun-Biotech, conducted in China
5
In collaboration with Eisai
6
In collaboration with Gilead
7
In collaboration with Astellas/Pfizer
8
In collaboration with Daiichi Sankyo
9
Sponsored by U.S. National Cancer Institute (NCI)/led by NRG Oncology
10
In collaboration with Taiho Pharmaceutical Co. Ltd and Astex Pharmaceuticals (UK), a wholly owned subsidiary of Otsuka Pharmaceutical Co., Ltd
About intismeran autogene
Intismeran autogene (intismeran; V940 or mRNA-4157) is a novel, potential first-in-class investigational messenger RNA (mRNA)-based individualized neoantigen therapy (INT) jointly developed by Merck and Moderna. Intismeran is designed and produced using a patient's tumor sample to identify the unique mutational signature, or "fingerprint," of their cancer and generate an anti-tumor immune response. Each therapy consists of a synthetic mRNA coding for up to 34 neoantigens and is tailored to the unique biology of an individual patient's tumor. Upon administration, the RNA-encoded neoantigen sequences are translated in the body and presented to the immune system, a key step in generating specific T-cell responses against cancer cells. Individualized neoantigen therapies are designed to train and activate an anti-tumor immune response based on the unique mutational signature of a patient's tumor. Merck and Moderna are advancing the robust
INTerpath clinical development program
evaluating the safety and efficacy of intismeran in combination with KEYTRUDA and other anti-cancer therapies, and as a monotherapy.
About sacituzumab tirumotecan (sac-TMT)
Sac-TMT is an investigational TROP2-directed ADC with a belotecan-derived topoisomerase I inhibitor payload and a unique bifunctional linker designed with the potential to maximize payload delivery to tumor cells and minimize payload loss while circulating in the body.
TROP2 is overexpressed on tumor cells compared to healthy cells in many common cancers, and through the TroFuse clinical development program, Merck is evaluating sac-TMT in 18 ongoing global Phase 3 trials across multiple tumor types, the broadest range of disease and treatment settings compared to any TROP2-directed ADC to date. The
TroFuse development program
spans early-to-late-stage disease in more than nine disease areas and includes more than 15,000 patients worldwide. Numerous Phase 3 trials are exploring sac-TMT as monotherapy and in combination with immunotherapies, aiming to improve survival and quality of life for patients with advanced and earlier-stage cancers.
About calderasib
Calderasib (MK-1084) is an investigational, highly potent and specific next-generation
KRAS
G12C covalent inhibitor. Mutations in
KRAS
are among the most prevalent mutations found in cancer, occurring with high frequency in non-small cell lung cancer (NSCLC), pancreatic, urogenital and colorectal cancers. The
KRAS
G12C mutation is the most frequently observed
KRAS
mutation in patients, occurring in approximately 14% of patients with NSCLC (adenocarcinoma). Despite decades of research and recognition of the therapeutic importance of targeting
KRAS
, the development of small molecule inhibitors targeting
KRAS
mutations has been challenging.
About KEYTRUDA
®
(pembrolizumab) injection for intravenous use, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 2,800 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected Indications in the U.S. for KEYTRUDA
®
(pembrolizumab)
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-authorized test, with no EGFR or ALK genomic tumor aberrations, and is:
Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-authorized test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Head and Neck Squamous Cell Cancer
KEYTRUDA is indicated for the treatment of adult patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-authorized test, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin and then as a single agent.
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-authorized test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Urothelial Cancer
KEYTRUDA, in combination with enfortumab vedotin-ejfv, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:
who are not eligible for any platinum-containing chemotherapy, or
who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
KEYTRUDA, in combination with enfortumab vedotin-ejfv, as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment, is indicated for the treatment of adult patients with muscle invasive bladder cancer (MIBC).
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA, in combination with lenvatinib, is indicated for the first-line treatment of adult patients with advanced RCC.
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
KEYTRUDA, in combination with belzutifan, is indicated for the adjuvant treatment of adult patients with RCC with a clear cell component (ccRCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.
KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not MSI-H as determined by an FDA-authorized test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
KEYTRUDA, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-authorized test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Contacts
Media Contacts:
Julie Cunningham
julie.cunningham@merck.com
Justine Moore
justine.moore@merck.com
Investor Contacts:
Peter Dannenbaum
(732) 594-1579
Steven Graziano
(732) 594-1583
Read full story here
Clinical ResultPhase 3Phase 1Phase 2ADC
28 Sep 2026
Merck & Co. has become the latest pharma to jump on the KRAS G12D bandwagon, paying $400 million to China’s SciBrunch for a preclinical candidate.
In return for the worldwide rights to the therapy, dubbed SPR2015, Merck has also agreed to milestone payments that could bring the deal’s total value up to $2.13 billion across “multiple indications,” according to a Sept. 28 release .
KRAS is a frequently mutated oncogene, but the lack of well-defined binding pockets rendered the proteins undruggable for years. With Amgen and Mirati Therapeutics showing KRAS G12C can be drugged by Lumakras and Krazati, interest in hitting other KRAS variants has increased in recent years.
KRAS G12D, a mutation found in about 38% of pancreatic cancer patients, is at the center of the next wave of programs. This has included Bayer penning a $1.3 billion biobucks deal with Kumquat Biosciences for a preclinical asset.
Merck already has a KRAS drug in the clinic in the form of the KRAS G12C inhibitor calderasib, which is in phase 3 trials for colorectal cancer and non-small cell lung cancer. Today’s deal with SciBrunch means the U.S. pharma now also has a bet placed on KRAS G12D.
“Evidence continues to accumulate for the therapeutic potential of targeting the KRAS pathway, a well-characterized factor in tumor cell growth,” George Addona, senior vice president, discovery, preclinical development and translational medicine, Merck Research Laboratories, said in the release.
“This agreement complements and diversifies our expanding pipeline of precision targeted candidates with SPR2015, a potent engineered inhibitor for one of the most prevalent mutant forms of KRAS found in human cancers,” Addona added.
Merck pointed out that SPR2015 has already demonstrated “nanomolar antiproliferative activities in various KRAS G12D-mutant cell lines while maintaining good selectivity over KRAS wildtype cells.”
Shanghai-based SciBrunch was founded two years ago by entrepreneur Tao Hu, Ph.D., and medicinal chemist Yang Zhang, Ph.D. The biotech has already taken its lead candidate , a brain-penetrant PARP1-selective inhibitor for a range of cancers, into the clinic, bankrolled by $65 million raised across two funding rounds.
“Since our founding, SciBrunch has remained focused on advancing innovative therapies targeting the RAS pathway and is committed to delivering transformative treatment options for patients with pancreatic, colorectal, lung and other major malignant tumors,” Hu said in the release.
Phase 3License out/in
100 Deals associated with Calderasib
Login to view more data
R&D Status
10 top R&D records. to view more data
Login
| Indication | Highest Phase | Country/Location | Organization | Date |
|---|---|---|---|---|
| Locally Advanced Lung Non-Small Cell Carcinoma | Phase 3 | United States | 18 Jun 2026 | |
| Locally Advanced Lung Non-Small Cell Carcinoma | Phase 3 | United States | 18 Jun 2026 | |
| Locally Advanced Lung Non-Small Cell Carcinoma | Phase 3 | United States | 18 Jun 2026 | |
| Locally Advanced Lung Non-Small Cell Carcinoma | Phase 3 | Japan | 18 Jun 2026 | |
| Locally Advanced Lung Non-Small Cell Carcinoma | Phase 3 | Japan | 18 Jun 2026 | |
| Locally Advanced Lung Non-Small Cell Carcinoma | Phase 3 | Japan | 18 Jun 2026 | |
| Locally Advanced Lung Non-Small Cell Carcinoma | Phase 3 | Argentina | 18 Jun 2026 | |
| Locally Advanced Lung Non-Small Cell Carcinoma | Phase 3 | Argentina | 18 Jun 2026 | |
| Locally Advanced Lung Non-Small Cell Carcinoma | Phase 3 | Argentina | 18 Jun 2026 | |
| Locally Advanced Lung Non-Small Cell Carcinoma | Phase 3 | Australia | 18 Jun 2026 |
Login to view more data
Clinical Result
Clinical Result
Indication
Phase
Evaluation
View All Results
| Study | Phase | Population | Analyzed Enrollment | Group | Results | Evaluation | Publication Date |
|---|
Phase 1 | 193 | hmmaohtgxf(jnaxdafqdk) = ipiticryeq muatcctisc (veyjbihjzy, 58 - 82) View more | Positive | 23 Oct 2026 | |||
hmmaohtgxf(jnaxdafqdk) = qpywghaziw muatcctisc (veyjbihjzy, 88 - 98) View more | |||||||
Phase 1 | KRAS G12C mutation Solid Tumors KRAS G12C mutation | 60 | irpisrgjyt(ceyxoqfliz) = tldeylpwox uzbnrturua (zqljikdfqx, 18 - 43) View more | Positive | 23 Oct 2026 | ||
Phase 1/2 | 190 | kzscdzdwvb(cvqtregkar) = pnjdtadsvj swtdvafgef (ndaswipcqv, 4.4 - 8.3) View more | Positive | 12 Sep 2026 | |||
Calderasib + sac-TMT | kketbtwsvp(lntsgzwlgc) = fzinrucvwg sofggteqnf (irfyeckkfk ) View more | ||||||
Phase 3 | 400 | Calderasib+pembrolizumab SC | rersubncqi(ujgedpbfru) = zhygbyasrv iflsoevxbk (mzgrugxhec, 85 - 93) View more | Positive | 12 Sep 2026 | ||
Placebo + pembrolizumab SC | ywwyfcajjp(oxecsrmrdm) = omemnlblyw kwpbjvtpcb (drtqjhagfk, 32 - 49) View more | ||||||
Phase 1/2 | 140 | nudkbxnazx(peyfjlhaia) = dbgthbfdko vabxpouwsv (ptsdiprcgf ) View more | Positive | 11 Sep 2026 | |||
xdarymrszd(wwhjeqghix) = yhttnzmmoy qrdslwgnqn (gwhpltheod ) View more | |||||||
Phase 3 | 675 | Calderasib plus subcutaneous pembrolizumab | qcpluoiyma(wgwsnxidls) = ekmuxialma sgkucluosj (kgaqfjzfpo, 9.3 - 15.3) View more | Positive | 11 Sep 2026 | ||
Subcutaneous pembrolizumab plus chemotherapy | qcpluoiyma(wgwsnxidls) = zphqeajaso sgkucluosj (kgaqfjzfpo, 7.2 - 10.9) View more | ||||||
Phase 3 | 477 | pvonwbiybr(kzuuuiqkxy) = pbrnnezoxg cqiujaqxvs (iqrhftjrds ) | Positive | 11 Sep 2026 | |||
pvonwbiybr(kzuuuiqkxy) = elmapriefn cqiujaqxvs (iqrhftjrds ) | |||||||
Phase 2 | 88 | eznhcewkac(gjzbcnfcze) = nynmgozxpq xpnhrwzmgj (kqtlqttxgg ) View more | Positive | 11 Sep 2026 | |||
eznhcewkac(gjzbcnfcze) = dugmshiqev xpnhrwzmgj (kqtlqttxgg ) View more | |||||||
Phase 2 | KRAS G12C mutation Solid Tumors KRAS G12C | 68 | zqnrabkqem(oxddtpijll) = cwbkhtqgnh jwmcjujcpf (apxlgoajcf, 11.4 - 17.0) | Positive | 29 May 2026 | ||
Phase 3 | metastatic non-small cell lung cancer First line KRAS G12C mutation | PD-L1 Tumor Proportion Score ≥50% | 400 | bcfpbwuski(wwyujpxvjp) = qabihfzhlv nwacsjctob (egywynclzn ) View more | Positive | 10 Sep 2025 | ||
Pembrolizumab plus placebo | bcfpbwuski(wwyujpxvjp) = qaimnvjxgv nwacsjctob (egywynclzn ) |
Login to view more data
Translational Medicine
Boost your research with our translational medicine data.
login
or
Deal
Boost your decision using our deal data.
login
or
Core Patent
Boost your research with our Core Patent data.
login
or
Clinical Trial
Identify the latest clinical trials across global registries.
login
or
Approval
Accelerate your research with the latest regulatory approval information.
login
or
Regulation
Understand key drug designations in just a few clicks with Synapse.
login
or
Hiro LS Researcher
The AI Search Engine Built to Accelerate Biopharma Decisions
Search across billion-scale life sciences data to uncover signals, validate evidence, and act with confidence.
Ask any biopharma research question→
Get started for free today!
Accelerate Strategic R&D decision making with Synapse, Patsnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.
Discover Synapse Data Servers
Synapse data is now integrated into the PatSnap LS Model Context Protocol (MCP) service. Customize your LLM agent now using our MCP server!
Bio
Bio Sequences Search & Analysis
Sign up for free
Chemical
Chemical Structures Search & Analysis
Sign up for free