Anti-EGFR (Micromedmark Biotech)

LUMAKRAS ® (sotorasib) Demonstrated Delayed Time to CNS Progression, Longer CNS PFS and Higher Intracranial ORR vs Docetaxel in Post-Hoc Analysis of Phase 3 CodeBreaK 200 Trial LUMAKRAS Shows Improved PFS vs Docetaxel Across Key Co-Alteration Subgroups in the Phase 3 CodeBreaK 200 Study LUMAKRAS Plus Vectibix ® (panitumumab) and FOLFIRI Combination Show ORR of 55% in Previously Treated KRAS G12C-Mutated Metastatic CRC THOUSAND OAKS, Calif., June 4, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the presentation of new data from the CodeBreaK clinical trial program, the most comprehensive global development program in patients with KRAS G12C-mutated cancers, at the American Society of Clinical Oncology (ASCO) Annual Meeting taking place June 2-6 in Chicago. The research presented reinforces the efficacy of LUMAKRAS®/LUMYKRAS® (sotorasib) in advanced non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (mCRC). Additionally, data from SCARLET, an Amgen funded investigator study sponsored by the West Japan Oncology Group, will be presented on June 6 and is the first study to highlight the safety and efficacy of sotorasib in combination with platinum-based chemotherapy for frontline treatment of patients with advanced NSCLC harboring a KRAS G12C mutation. "As the leader in KRAS inhibition, Amgen continues to advance the CodeBreaK program by evaluating LUMAKRAS across different indications and combinations to potentially help more people living with KRAS G12C-mutated cancers," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "These data presented at ASCO underscore the clinical importance of LUMAKRAS, including the only randomized trial of a KRASG12C inhibitor to show higher intracranial activity compared to chemotherapy, along with data validating our combination treatment approach in metastatic colorectal cancer, where new precision medicine strategies are desperately needed." Improved CNS Activity in Advanced NSCLC In the first and only randomized study for any KRASG12C inhibitor, data from a post-hoc analysis of the global Phase 3 CodeBreaK 200 trial included patients with advanced NSCLC and treated/stable central nervous system (CNS) lesions at baseline, as assessed by a blinded independent central review (BICR). In this analysis using a modified exploratory response assessment in neuro-oncology brain metastases (RANO-BM), LUMAKRAS demonstrated delayed time to CNS progression and longer CNS progression-free survival (PFS) compared with docetaxel. Additionally, the CNS objective response rate (ORR),* an assessment of CNS tumor shrinkage following treatment, was more than double (33.3% vs 15.4%) in patients treated with LUMAKRAS (n= 18) compared to docetaxel (n= 13). The safety profile in this analysis was similar to the CodeBreaK 200 overall population. "CNS metastases are an unfortunately common complication of KRAS G12C-mutated advanced NSCLC, occurring in about 30–40% of patients," said Melissa L. Johnson, M.D., director of Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology. "In this post-hoc analysis from CodeBreaK 200, sotorasib delayed CNS progression-free survival by more than five months and is a potential clinically meaningful benefit for second-line NSCLC patients with KRAS G12C mutations." These results will be presented on Sunday, June 4, as a late-breaking abstract in a poster discussion session: Lung Cancer—Non-Small Cell Metastatic, beginning at 4:30 p.m. CDT. (#LBA9016). *Exploratory post-hoc analysis in patients with stable/treated CNS lesions at baseline, in which measurable lesions were defined per study as CNS lesions ≥10 mm in diameter by BICR using modified RANO-BM Criteria New NSCLC Biomarker Data from CodeBreaK 200 Show Consistent Clinical Benefit Across Subgroups In the first randomized, molecularly-defined analysis of a KRASG12C inhibitor versus chemotherapy, LUMAKRAS showed improved PFS over docetaxel, irrespective of PD-L1 expression level, and retained PFS benefit versus docetaxel across key co-alteration subgroups (including STK11, KEAP1, TP53). Collectively, the biomarker data help inform treatment decision making and the ongoing CodeBreaK clinical development program, which explores LUMAKRAS in novel combinations. These data will be presented on Tuesday, June 6 during an oral abstract session: Lung Cancer–Non-Small Cell Metastatic, from 9:45 a.m.- 12:45 p.m. CDT (Abstract #9008). Encouraging Safety and Efficacy in Metastatic CRC Data from the CodeBreaK 101 Phase 1B study, the first reported results for the combination of LUMAKRAS with Vectibix® (panitumumab) and FOLFIRI, showed encouraging safety and efficacy in previously-treated KRAS G12C-mutated metastatic CRC. Among 42 patients evaluable for response, confirmed ORR was 55% (95% CI: 38.7, 70.2), and disease control rate (DCR) was 93% (95% CI: 80.5, 98.5), with responses observed regardless of the number of prior lines of therapy and regardless of progression on prior irinotecan-based therapy. LUMAKRAS plus Vectibix and FOLFIRI combination reported adverse events consistent with those expected for the therapies under study. "A priority in KRAS G12C-mutated colorectal cancer research is exploring new treatment combinations that can drastically improve response rates attained with current treatments, which can be as low as 2%," said lead investigator, David S. Hong, M.D., professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, Houston. "These results showed encouraging efficacy with sotorasib in combination with panitumumab and FOLFIRI, and importantly showed consistent safety for each product." These data will be presented on Monday, June 5 during a poster discussion session: Gastrointestinal Cancer—Colorectal and Anal, from 1:15-2:45 p.m. CDT (Abstract #3513.) More information on Amgen's abstracts is available on the ASCO website. About LUMAKRAS®/LUMYKRAS® (sotorasib) Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS/LUMYKRAS, a KRASG12C inhibitor.i LUMAKRAS/LUMYKRAS has demonstrated a positive benefit-risk profile with rapid, deep, and durable anticancer activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation.ii Amgen is progressing the largest and broadest global KRASG12C inhibitor development program with unparalleled speed and exploring more than 10 sotorasib combination regimens, with clinical trial sites spanning five continents. To date, over 6,500 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program and commercial use. In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval with its approval in the U.S., under accelerated approval. LUMAKRAS/LUMYKRAS is also approved in the European Union, Japan, United Arab Emirates, South Korea, Hong Kong, Switzerland, Taiwan, Qatar, and in Australia, Brazil, Canada, Great Britain, Singapore, and Israel under the FDA's Project Orbis. Additionally, Amgen has submitted MAAs in Argentina, Colombia, Kuwait, Macao, Malaysia, Mexico, Russia, Saudi Arabia, Thailand and Turkey. LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.iii About Non-Small Cell Lung Cancer and the KRAS G12C Mutation Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.iv Overall survival rates for NSCLC are improving but remain poor for patients with advanced disease, and 5-year survival is only 9% for those with metastatic disease.v KRAS G12C is the most common KRAS mutation in NSCLC.vi About 13% of patients with NSCLC harbor the KRAS G12C mutation.[vii] Unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working. The outcomes with other approved therapies are suboptimal, with a median progression-free survival of approximately four months following second-line treatment of KRAS G12C-mutated NSCLC.viii About Advanced Colorectal Cancer and the KRAS G12C Mutation Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, comprising 10% of all cancer diagnoses.ix It is also the third most commonly diagnosed cancer globally.x Patients with previously treated metastatic CRC need more effective treatment options. For patients in the third-line setting, standard therapies yield median PFS times of about two months and patients' response rates are less than 2%.xi,xii KRAS mutations are among the most common genetic alterations in colorectal cancers, with the KRAS G12C mutation present in approximately 3-5% of colorectal cancers.xiii,xiv,xv About CodeBreaK  The CodeBreaK clinical development program for Amgen's drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.  CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors.xvi Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline.ii The Phase 2 trial in metastatic colorectal cancer (mCRC) is fully enrolled and results have been published.xvii CodeBreaK 200, the global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in KRAS G12C-mutated NSCLC completed enrollment of 345 patients. Eligible patients had previously treated, locally advanced and unresectable or metastatic KRAS G12C-mutated NSCLC. The primary endpoint is progression-free survival and key secondary endpoints include overall survival, objective response rate, and patient-reported outcomes.xviii Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.xix A Phase 2 randomized study will evaluate sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment (CodeBreaK 201).xx LUMAKRAS® (sotorasib) U.S. Indication LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). LUMAKRAS® (sotorasib) Important U.S. Safety Information Hepatotoxicity LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis. Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity. Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction. Interstitial Lung Disease (ILD)/Pneumonitis LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified. Most Common Adverse Reactions The most common adverse reactions occurring in ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough. Drug Interactions Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products. Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS. If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid. Please see LUMAKRAS full Prescribing Information.  About Vectibix® (panitumumab) Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC. In June 2017, the FDA approved a refined indication for Vectibix for use in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) mCRC. INDICATION AND LIMITATION OF USE Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC): as first-line therapy in combination with FOLFOX, and as monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. Limitation of Use: Vectibix® is not indicated for the treatment of patients with RAS mutant mCRC or for whom RAS mutation status is unknown. IMPORTANT SAFETY INFORMATION BOXED WARNING: DERMATOLOGIC TOXICITY Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)]. In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix®. The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Monitor patients who develop dermatologic or soft tissue toxicities while on Vectibix® for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix®. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix®. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune- related effects (e.g., Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix® for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix® concerning dermatologic toxicity are provided in the product labeling. Vectibix® is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as "RAS." Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS-mutant mCRC tumors received Vectibix® in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix® and FOLFOX versus FOLFOX alone. Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix® treatment, periodically during Vectibix® treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate. In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix® administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions. Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix® in combination with chemotherapy. Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix®. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix®. In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix® therapy. Discontinue Vectibix® therapy if ILD is confirmed. In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix® versus the risk of pulmonary complications must be carefully considered. Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix®. Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix® use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix® for acute or worsening keratitis. In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix®-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0). NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix®-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix®-treated patients. As a result of the toxicities experienced, patients randomized to Vectibix®, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy. Vectibix® can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix®. In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix® were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea. The most commonly reported adverse reactions (≥ 20%) with Vectibix® + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration. To see the Vectibix® Prescribing Information, including Boxed Warning, visit . About Amgen Oncology At Amgen Oncology, our mission to serve patients drives all that we do. That's why we're relentlessly focused on accelerating the delivery of medicines that have the potential to empower all angles of care and transform lives of people with cancer. For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company's history, moving with great speed to advance those innovations for the patients who need them. For more information, follow us on . About Amgen Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2022, Amgen was named one of the "World's Best Employers" by Forbes and one of "America's 100 Most Sustainable Companies" by Barron's. For more information, visit Amgen.com and follow us on Twitter, LinkedIn, Instagram, TikTok and YouTube. Amgen Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. 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The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. CONTACT: Amgen, Thousand Oaks Michael Strapazon, 805-313-5553 (media) Jessica Akopyan, 805-440-5721 (media) Arvind Sood, 805-447-1060 (investors) _______________________________ i Canon J, et al. Nature. 2019;575: 217–223. ii Skoulidis F, et al. N Engl J Med. 2021;384:2371-2381. iii Hong DS, et al. N Engl J Med. 2020;383:1207-1217. iv Sung H, et al. CA Cancer J Clin. 2021;71:209-249. v American Cancer Society. Lung Cancer Survival Rates. 2023. Available at: . Accessed on June 2, 2023. vi Arbour KC, et al. Clin Cancer Res. 2018;24:334-340. vii Nassar AF, et al. N Engl J. Med. 2021;384:185-187. viii Spira Al, et al. Lung Cancer. 2021;159:1-9. ix Rawla, P, et al. Gastroenterology Review. 2019;14(2):89-103. x World Health Organization. 2022 Statistics. Available at: . Accessed on June 2, 2023. xi Mayer RJ, et al. N Engl J Med. 2015;372(20):1909-1919. xii Grothey A, et al. Lancet. 2013;381(9863):303-312. xiii Neumann J, et al. Pathol Res Pract. 2009;205(12):858-862. xiv Jones RP, et al. Br J Cancer. 2017;116(7):923-929. xv Wiesweg M, et al. Oncogene. 2019;38(16):2953-2966. xvi ClinicalTrials.gov. CodeBreaK 100. 2023. Available at: . Accessed on June 2, 2023. xvii Fakih MG, et al. Lancet Oncol. 2022;23:115-124. xviii ClinicalTrials.gov. CodebreaK 200. 2023. Available at: . Accessed on June 2, 2023. xix ClinicalTrials.gov. CodeBreaK 101. 2023. Available at: . Accessed on June 2, 2023. xx ClinicalTrials.gov. CodeBreaK 201. 2023. Available at: . Accessed on June 2, 2023. SOURCE Amgen

LUMAKRAS ® (sotorasib) Demonstrated Delayed Time to CNS Progression, Longer CNS PFS and Higher Intracranial ORR vs Docetaxel in Post-Hoc Analysis of Phase 3 CodeBreaK 200 Trial LUMAKRAS Shows Improved PFS vs Docetaxel Across Key Co-Alteration Subgroups in the Phase 3 CodeBreaK 200 Study LUMAKRAS Plus Vectibix® (panitumumab) and FOLFIRI Combination Show ORR of 55% in Previously Treated KRAS G12C-Mutated Metastatic CRC THOUSAND OAKS, Calif., June 4, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the presentation of new data from the CodeBreaK clinical trial program, the most comprehensive global development program in patients with KRAS G12C-mutated cancers, at the American Society of Clinical Oncology (ASCO) Annual Meeting taking place June 2-6 in Chicago. The research presented reinforces the efficacy of LUMAKRAS®/LUMYKRAS® (sotorasib) in advanced non-small cell lung cancer (NSCLC) and metastatic colorectal cancer (mCRC). Additionally, data from SCARLET, an Amgen funded investigator study sponsored by the West Japan Oncology Group, will be presented on June 6 and is the first study to highlight the safety and efficacy of sotorasib in combination with platinum-based chemotherapy for frontline treatment of patients with advanced NSCLC harboring a KRAS G12C mutation. "As the leader in KRAS inhibition, Amgen continues to advance the CodeBreaK program by evaluating LUMAKRAS across different indications and combinations to potentially help more people living with KRAS G12C-mutated cancers," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "These data presented at ASCO underscore the clinical importance of LUMAKRAS, including the only randomized trial of a KRASG12C inhibitor to show higher intracranial activity compared to chemotherapy, along with data validating our combination treatment approach in metastatic colorectal cancer, where new precision medicine strategies are desperately needed." Improved CNS Activity in Advanced NSCLC In the first and only randomized study for any KRASG12C inhibitor, data from a post-hoc analysis of the global Phase 3 CodeBreaK 200 trial included patients with advanced NSCLC and treated/stable central nervous system (CNS) lesions at baseline, as assessed by a blinded independent central review (BICR). In this analysis using a modified exploratory response assessment in neuro-oncology brain metastases (RANO-BM), LUMAKRAS demonstrated delayed time to CNS progression and longer CNS progression-free survival (PFS) compared with docetaxel. Additionally, the CNS objective response rate (ORR),* an assessment of CNS tumor shrinkage following treatment, was more than double (33.3% vs 15.4%) in patients treated with LUMAKRAS (n= 18) compared to docetaxel (n= 13). The safety pro this analysis was similar to the CodeBreaK 200 overall population. "CNS metastases are an unfortunately common complication of KRAS G12C-mutated advanced NSCLC, occurring in about 30–40% of patients," said Melissa L. Johnson, M.D., director of Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology. "In this post-hoc analysis from CodeBreaK 200, sotorasib delayed CNS progression-free survival by more than five months and is a potential clinically meaningful benefit for second-line NSCLC patients with KRAS G12C mutations." These results will be presented on Sunday, June 4, as a late-breaking abstract in a poster discussion session: Lung Cancer—Non-Small Cell Metastatic, beginning at 4:30 p.m. CDT. (#LBA9016). *Exploratory post-hoc analysis in patients with stable/treated CNS lesions at baseline, in which measurable lesions were defined per study as CNS lesions ≥10 mm in diameter by BICR using modified RANO-BM Criteria New NSCLC Biomarker Data from CodeBreaK 200 Show Consistent Clinical Benefit Across Subgroups In the first randomized, molecularly-defined analysis of a KRASG12C inhibitor versus chemotherapy, LUMAKRAS showed improved PFS over docetaxel, irrespective of PD-L1 expression level, and retained PFS benefit versus docetaxel across key co-alteration subgroups (including STK11, KEAP1, TP53). Collectively, the biomarker data help inform treatment decision making and the ongoing CodeBreaK clinical development program, which explores LUMAKRAS in novel combinations. These data will be presented on Tuesday, June 6 during an oral abstract session: Lung Cancer–Non-Small Cell Metastatic, from 9:45 a.m.- 12:45 p.m. CDT (Abstract #9008). Encouraging Safety and Efficacy in Metastatic CRC Data from the CodeBreaK 101 Phase 1B study, the first reported results for the combination of LUMAKRAS with Vectibix® (panitumumab) and FOLFIRI, showed encouraging safety and efficacy in previously-treated KRAS G12C-mutated metastatic CRC. Among 42 patients evaluable for response, confirmed ORR was 55% (95% CI: 38.7, 70.2), and disease control rate (DCR) was 93% (95% CI: 80.5, 98.5), with responses observed regardless of the number of prior lines of therapy and regardless of progression on prior irinotecan-based therapy. LUMAKRAS plus Vectibix and FOLFIRI combination reported adverse events consistent with those expected for the therapies under study. "A priority in KRAS G12C-mutated colorectal cancer research is exploring new treatment combinations that can drastically improve response rates attained with current treatments, which can be as low as 2%," said lead investigator, David S. Hong, M.D., professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, Houston. "These results showed encouraging efficacy with sotorasib in combination with panitumumab and FOLFIRI, and importantly showed consistent safety for each product." These data will be presented on Monday, June 5 during a poster discussion session: Gastrointestinal Cancer—Colorectal and Anal, from 1:15-2:45 p.m. CDT (Abstract #3513.) More information on Amgen's abstracts is available on the ASCO website. About LUMAKRAS®/LUMYKRAS® (sotorasib) Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS/LUMYKRAS, a KRASG12C inhibitor.i LUMAKRAS/LUMYKRAS has demonstrated a positive benefit-risk pro rapid, deep, and durable anticancer activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation.ii Amgen is progressing the largest and broadest global KRASG12C inhibitor development program with unparalleled speed and exploring more than 10 sotorasib combination regimens, with clinical trial sites spanning five continents. To date, over 6,500 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program and commercial use. In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval with its approval in the U.S., under accelerated approval. LUMAKRAS/LUMYKRAS is also approved in the European Union, Japan, United Arab Emirates, South Korea, Hong Kong, Switzerland, Taiwan, Qatar, and in Australia, Brazil, Canada, Great Britain, Singapore, and Israel under the FDA's Project Orbis. Additionally, Amgen has submitted MAAs in Argentina, Colombia, Kuwait, Macao, Malaysia, Mexico, Russia, Saudi Arabia, Thailand and Turkey. LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.iii About Non-Small Cell Lung Cancer and the KRAS G12C Mutation Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.iv Overall survival rates for NSCLC are improving but remain poor for patients with advanced disease, and 5-year survival is only 9% for those with metastatic disease.v KRAS G12C is the most common KRAS mutation in NSCLC.vi About 13% of patients with NSCLC harbor the KRAS G12C mutation.[vii] Unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working. The outcomes with other approved therapies are suboptimal, with a median progression-free survival of approximately four months following second-line treatment of KRAS G12C-mutated NSCLC.viii About Advanced Colorectal Cancer and the KRAS G12C Mutation Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, comprising 10% of all cancer diagnoses.ix It is also the third most commonly diagnosed cancer globally.x Patients with previously treated metastatic CRC need more effective treatment options. For patients in the third-line setting, standard therapies yield median PFS times of about two months and patients' response rates are less than 2%.xi,xii KRAS mutations are among the most common genetic alterations in colorectal cancers, with the KRAS G12C mutation present in approximately 3-5% of colorectal cancers.xiii,xiv,xv About CodeBreaK The CodeBreaK clinical development program for Amgen's drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers. CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors.xvi Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline.ii The Phase 2 trial in metastatic colorectal cancer (mCRC) is fully enrolled and results have been published.xvii CodeBreaK 200, the global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in KRAS G12C-mutated NSCLC completed enrollment of 345 patients. Eligible patients had previously treated, locally advanced and unresectable or metastatic KRAS G12C-mutated NSCLC. The primary endpoint is progression-free survival and key secondary endpoints include overall survival, objective response rate, and patient-reported outcomes.xviii Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.xix A Phase 2 randomized study will evaluate sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment (CodeBreaK 201).xx LUMAKRAS® (sotorasib) U.S. Indication LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). LUMAKRAS® (sotorasib) Important U.S. Safety Information Hepatotoxicity LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis. Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity. Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction. Interstitial Lung Disease (ILD)/Pneumonitis LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified. Most Common Adverse Reactions The most common adverse reactions occurring in ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough. Drug Interactions Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products. Inform patients to avoid proton pump inhibitors and H2 receptor antagonists while taking LUMAKRAS. If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid. Please see LUMAKRAS full Prescribing Information. About Vectibix® (panitumumab) Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC. In June 2017, the FDA approved a refined indication for Vectibix for use in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) mCRC. INDICATION AND LIMITATION OF USE Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC): as first-line therapy in combination with FOLFOX, and as monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. Limitation of Use: Vectibix® is not indicated for the treatment of patients with RAS mutant mCRC or for whom RAS mutation status is unknown. IMPORTANT SAFETY INFORMATION BOXED WARNING: DERMATOLOGIC TOXICITY Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)]. In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix®. The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Monitor patients who develop dermatologic or soft tissue toxicities while on Vectibix® for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix®. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix®. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune- related effects (e.g., Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix® for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix® concerning dermatologic toxicity are provided in the product labeling. Vectibix® is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as "RAS." Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS-mutant mCRC tumors received Vectibix® in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix® and FOLFOX versus FOLFOX alone. Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix® treatment, periodically during Vectibix® treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate. In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix® administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions. Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix® in combination with chemotherapy. Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix®. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix®. In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix® therapy. Discontinue Vectibix® therapy if ILD is confirmed. In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix® versus the risk of pulmonary complications must be carefully considered. Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix®. Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix® use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix® for acute or worsening keratitis. In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix®-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0). NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix®-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix®-treated patients. As a result of the toxicities experienced, patients randomized to Vectibix®, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy. Vectibix® can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix®. In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix® were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea. The most commonly reported adverse reactions (≥ 20%) with Vectibix® + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration. To see the Vectibix® Prescribing Information, including Boxed Warning, visit . About Amgen Oncology At Amgen Oncology, our mission to serve patients drives all that we do. That's why we're relentlessly focused on accelerating the delivery of medicines that have the potential to empower all angles of care and transform lives of people with cancer. For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company's history, moving with great speed to advance those innovations for the patients who need them. For more information, follow us on . About Amgen Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2022, Amgen was named one of the "World's Best Employers" by Forbes and one of "America's 100 Most Sustainable Companies" by Barron's. For more information, visit Amgen.com and follow us on Twitter, LinkedIn, Instagram, TikTok and YouTube. Amgen Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. 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The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. CONTACT: Amgen, Thousand Oaks Michael Strapazon, 805-313-5553 (media) Jessica Akopyan, 805-440-5721 (media) Arvind Sood, 805-447-1060 (investors) _______________________________ i Canon J, et al. Nature. 2019;575: 217–223. ii Skoulidis F, et al. N Engl J Med. 2021;384:2371-2381. iii Hong DS, et al. N Engl J Med. 2020;383:1207-1217. iv Sung H, et al. CA Cancer J Clin. 2021;71:209-249. v American Cancer Society. Lung Cancer Survival Rates. 2023. Available at: . Accessed on June 2, 2023. vi Arbour KC, et al. Clin Cancer Res. 2018;24:334-340. vii Nassar AF, et al. N Engl J. Med. 2021;384:185-187. viii Spira Al, et al. Lung Cancer. 2021;159:1-9. ix Rawla, P, et al. Gastroenterology Review. 2019;14(2):89-103. x World Health Organization. 2022 Statistics. Available at: . Accessed on June 2, 2023. xi Mayer RJ, et al. N Engl J Med. 2015;372(20):1909-1919. xii Grothey A, et al. Lancet. 2013;381(9863):303-312. xiii Neumann J, et al. Pathol Res Pract. 2009;205(12):858-862. xiv Jones RP, et al. Br J Cancer. 2017;116(7):923-929. xv Wiesweg M, et al. Oncogene. 2019;38(16):2953-2966. xvi ClinicalTrials.gov. CodeBreaK 100. 2023. Available at: . Accessed on June 2, 2023. xvii Fakih MG, et al. Lancet Oncol. 2022;23:115-124. xviii ClinicalTrials.gov. CodebreaK 200. 2023. Available at: . Accessed on June 2, 2023. xix ClinicalTrials.gov. CodeBreaK 101. 2023. Available at: . Accessed on June 2, 2023. xx ClinicalTrials.gov. CodeBreaK 201. 2023. Available at: . Accessed on June 2, 2023. 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