olomorasib (LY3537982) / Eli Lilly - LARVOL DELTA

Intracranial efficacy of olomorasib, a second-generation KRAS G12C inhibitor, in patients with KRAS G12C-mutant NSCLC who have active, untreated brain metastases (ESMO 2025) - No abstract available

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Efficacy and Safety of 1L Olomorasib Plus Pembrolizumab in KRAS G12C-Mutant NSCLC: Results From LOXO-RAS-20001 and SUNRAY-01 (IASLC-WCLC 2025) - "Conclusions : In this merged dataset with double the number of 1L pts relative to previous presentations, olomorasib plus pembrolizumab continues to demonstrate a manageable safety profile and promising efficacy. These updated findings, including longer follow-up on LOXO-RAS-20001 pts, provide additional support for the ongoing Phase 3 SUNRAY-01 trial, comparing olomorasib (100 mg BID) plus pembrolizumab versus placebo plus pembrolizumab as 1L treatment in pts with KRAS G12C-mutant NSCLC and PD-L1 ≥50%."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • KRAS • PD-L1 • RAS

SUNRAY-02: A Phase 3 Study of Olomorasib and Immunotherapy in Stage II-III KRAS G12C-Mutant NSCLC After Definitive Therapy (IASLC-WCLC 2025) - P1/2, P3 | "The phase 1/2 LOXO-RAS-20001 study (NCT04956640) showed that olomorasib alone and in combination with pembrolizumab demonstrated promising preliminary efficacy and a favorable safety profile in patients with metastatic KRAS G12C-mutant NSCLC...In Part B, approximately 300 participants will be randomized in a 1:1 ratio to receive either olomorasib or placebo in combination with durvalumab...The primary endpoint for Part B is progression-free survival (PFS) by blinded independent central review. Secondary endpoints include OS, objective response rate (ORR), duration of response (DoR), disease control rate (DCR), time to response (TTR), progression-free survival 2 (PFS2), safety, changes in HRQoL, and patient-reported outcomes."

IO biomarker • P3 data • Immunology • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ALK • EGFR • KRAS • PD-L1

Efficacy and Safety of 1L Olomorasib + Chemoimmunotherapy in KRAS G12C-Mutant NSCLC: Results From LOXO-RAS-20001 and SUNRAY-01 (IASLC-WCLC 2025) - "Introduction : Olomorasib, a potent and selective second-generation KRAS G12C inhibitor, demonstrated promising antitumor activity and a manageable safety profile in first-line (1L) KRAS G12C-mutant advanced NSCLC in combination with pembrolizumab plus chemotherapy (chemoimmunotherapy). Moreover, efficacy remains promising in this higher-risk population, largely of pts with PD-L1 0-49%. These updated findings further support the ongoing Phase 3 SUNRAY-01 trial, comparing olomorasib (100 mg BID) plus chemoimmunotherapy versus placebo plus chemoimmunotherapy as 1L treatment in pts with KRAS G12C-mutant NSCLC and any PD-L1 level."

Clinical • IO biomarker • Anemia • Fatigue • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • KRAS • PD-L1

A Study of Olomorasib (LY3537982) in Participants With Hepatic Impairment and Healthy Participants (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Eli Lilly and Company | Recruiting ➔ Completed

Trial completion • Hepatitis C • Hepatology • Liver Failure

In an oral presentation (Abstract #MA02.06), Lilly will report on an integrated analysis of efficacy and safety results in patients with KRAS G12C-mutant NSCLC who received olomorasib plus pembrolizumab as first-line treatment in the dose optimization cohorts of the Phase 1/2 LOXO-RAS-20001 study and Phase 3 SUNRAY-01 study. (Eli Lilly Press Release) - "These data will be shared in an oral presentation during the New Treatment Strategies in Other Than EGFR-Positive Tumors session on Sunday, Sept. 7, 2025, from 12-1:15 p.m. Central European Summer Time (CEST)."

Clinical data • Non Small Cell Lung Cancer

In a second oral presentation (Abstract #OA08.02), Lilly will report results of an integrated analysis in patients with KRAS G12C-mutant advanced or metastatic NSCLC who received olomorasib in combination with chemoimmunotherapy (pembrolizumab, pemetrexed and platinum) as a first-line treatment in the Phase 1/2 LOXO-RAS-20001 trial and safety lead-in for the Phase 3 SUNRAY-01 trial. (Eli Lilly Press Release) - "These data will be shared in an oral presentation during the Improving Outcomes in EGFR and KRAS Mutant Tumors, More is Better session on Monday, Sept. 8, 2025, from 12-1:15 p.m. CEST."

Clinical data • Non Small Cell Lung Cancer

Eli Lilly and Company…announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to olomorasib, in combination with anti-PD-1 therapy KEYTRUDA (pembrolizumab), for the first-line treatment of patients with unresectable advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation and PD-L1 expression ≥ 50% (Eli Lilly Press Release) - "The FDA Breakthrough Therapy designation is based on encouraging results from the Phase 1/2 LOXO-RAS-20001 trial and the dose optimization portion of the Phase 3 SUNRAY-01 trial."

Breakthrough therapy • Evidence highlight • Non Small Cell Lung Cancer • KRAS

Process improvements towards Olomorasib (ACS-Fall 2025) - "Each of the fragments have been synthesized by multiple routes on production scale with each route improvement focusing on, for example, safety and environmental impact, and yield and selectivity. Select route choices and process improvements for this small molecule will be described."

Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Sarcoma • Solid Tumor • KRAS

A Study of LY3537982 in Participants With Kidney Problems Compared With Participants With Normal Kidney Function (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial • Nephrology • Renal Disease

A Study of Olomorasib (LY3537982) in Healthy Japanese Participants (clinicaltrials.gov) - P1 | N=188 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

Olomorasib: Primary completion of P3 SUNRAY01 trial (NCT06119581) for NSCLC in Oct 2026 (Eli Lilly) - Q2 2025 Results: Completion of P3 SUNRAY01 trial for NSCLC in Oct 2029; Primary completion of P3 SUNRAY02 trial (NCT06890598) for KRAS G12C-mutant NSCLC in May 2029; Completion of P3 SUNRAY02 trial for KRAS G12C-mutant NSCLC in Feb 2032

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Binding modes of the KRAS(G12C) inhibitors GDC-6036 and LY3537982 revealed by all atom molecular dynamics simulations. (PubMed, Sci Rep) - "While both inhibitors display low activity towards KRAS(WT), LY3537982 maintains high activity against other RAS isoforms with G12C mutation. As the simulation predictions align with the experimental results, our findings indicate that microsecond timescale simulations can be a valuable tool for predicting binding modes."

Journal • KRAS

The complex journey of targeting RAS in oncology. (PubMed, BMC Cancer) - "This breakthrough has led to the development of targeted therapeutics, such as sotorasib and adagrasib, for KRAS G12C-mutated non-small cell lung cancer (NSCLC)...New inhibitors, such as LY3537982 or GDC-6036, are promising, but achieving effective and selective RAS inhibition remains a significant challenge...Challenges such as off-target effects and delivery issues remain significant barriers in the introduction of effective therapies based on RAS inhibitors. This overview highlights the evolving nature of targeting RAS in cancer therapy."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • TP53

A Study of Multiple Olomorasib (LY3537982) Capsules in Healthy Participants (clinicaltrials.gov) - P1 | N=120 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

Eli Lilly's olomorasib granted orphan drug designation for NSCLC type (MSN News) - "The U.S. FDA has granted orphan drug designation for Eli Lilly's olomorasib for treatment of KRAS G12C-mutant non-small cell lung cancer. The candidate is in phase 3 for this indication. It is under examination for KRAS G12C-mutated cancers in combination with Keytruda (pembrolizumab) with or without chemotherapy for first-line treatment of advanced NSCLC."

Orphan drug • Non Small Cell Lung Cancer

Multicenter study of the impact of trial eligibility criteria on enrollment to KRAS G12C inhibitor trials in patients with non-small cell lung cancer. (ASCO 2025) - " We extracted EC for Phase I-III trials of six KRAS G12C inhibitors (sotorasib, adagrasib, olomorasib, divarasib, JDQ443 and RMC-6291) that were published or made available by sponsors. Our data indicate substantial differences between the real-world population of patients treated with KRAS G12C inhibitors and those who were trial eligible. Efforts should focus on improving clinical trial generalizability without compromising safety."

Clinical • Lung Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • KRAS

Safety and efficacy of olomorasib + immunotherapy in first-line treatment of patients with KRAS G12C-mutant advanced NSCLC: Update from the LOXO-RAS-20001 trial. (ASCO 2025) - P1/2, P3 | "Olomorasib + pembrolizumab in the 1L metastatic setting demonstrated favorable safety and encouraging antitumor activity in pts with KRAS G12C-mutant advanced NSCLC across all PD-L1 expression levels. A global, registrational study investigating this combination in 1L NSCLC is currently enrolling (SUNRAY-01, NCT06119581)."

Clinical • IO biomarker • Metastases • Dermatology • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pruritus • Solid Tumor • KRAS • PD-L1

Efficacy and safety of olomorasib, a second-generation KRAS G12C inhibitor, plus cetuximab in KRAS G12C-mutant advanced colorectal cancer. (ASCO 2025) - P1/2 | " Pts with advanced KRAS G12C-mutant CRC (tissue or plasma) previously treated with ≥1 prior oxaliplatin- or irinotecan-containing regimen were eligible and enrolled into dose escalation/expansion or optimization at 2 doses of olomorasib (100 and 150 mg, orally BID). Olomorasib + cetuximab demonstrated similar antitumor activity and favorable safety at both dose levels in pts with KRAS G12C-mutant CRC, with the optimal dose of olomorasib + cetuximab determined as 100 mg BID. These results further support combining second-generation KRAS G12Ci with other anticancer therapies to improve outcomes in previously treated pts with KRAS G12C-mutant CRC."

Clinical • Metastases • Colorectal Cancer • Dermatitis • Dermatology • Immunology • Oncology • Solid Tumor • KRAS

Gustave Roussy at the ASCO 2025 Congress (Gustave Roussy) - "For this 61st edition, Gustave Roussy’s physician-scientists have contributed to 109 presentations, with results being revealed during oral and poster sessions, but also during the prestigious plenary session."

Clinical data • Colorectal Cancer • Ewing Sarcoma • Squamous Cell Carcinoma of Head and Neck

Lilly announces details of presentations at 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (PRNewswire) - "Presentation Highlights:...(i) Olomorasib (investigational KRAS G12C inhibitor): In two oral presentations, Lilly will report updated results from a Phase 1/2 study of olomorasib, a potent and highly selective second-generation inhibitor of KRAS G12C with preliminary evidence of CNS activity, in combination with pembrolizumab in patients with KRAS G12C-mutant advanced non-small cell lung cancer (NSCLC) and in combination with cetuximab in patients with KRAS G12C-mutant colorectal cancer (CRC). The submitted abstracts utilized a November 13, 2024 data cut-off date, and the presentations will utilize a January 15, 2025 data cut-off date."

P1/2 data • Colorectal Cancer • Non Small Cell Lung Cancer

KRAS G12C inhibitors as monotherapy or in combination for metastatic colorectal cancer: A proportion and comparative meta-analysis of efficacy and toxicity from phase I-II-III trials. (PubMed, Crit Rev Oncol Hematol) - "This analysis suggests that KRAS-G12C inhibitors in combination with anti-EGFR agents may provide a doubled ORR and 1.5-month PFS benefit compared to monotherapy in previously treated mCRC patients, but with a doubled grade 3-4 TRAEs, including skin toxicities, paronychia, and hypomagnesemia. Treatment preferences should be individualized in these highly pretreated patients."

Journal • Monotherapy • P1/2 data • Retrospective data • Review • Colorectal Cancer • Oncology • Solid Tumor • KRAS

LY4050784, a selective inhibitor of SMARCA2, demonstrates synergistic activity in combinations with pembrolizumab or KRAS inhibitors (AACR 2025) - P1 | "LY4050784 demonstrated robust activity in vitro and in vivo when combined with standard lung cancer chemotherapies (paclitaxel, cisplatin, and pemetrexed)...Finally, we explored the activity of LY4050784 in combination with both mutant-selective KRAS G12C and G12D inhibitors (olomorasib and LY3962673, respectively) and the isoform-selective pan-KRAS inhibitor LY4066434...These results demonstrate that LY4050784 exhibits robust antitumor activity in combination with chemotherapy, pembrolizumab, and multiple KRAS inhibitors in preclinical models of SMARCA4-mutant cancers. Investigation of these combinations clinically is warranted"

IO biomarker • Colon Cancer • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS • SMARCA2 • SMARCA4

SUNRAY-02: Study of Olomorasib (LY3537982) in Combination With Standard of Care in Participants With Resected or Unresectable KRAS G12C-mutant Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=700 | Recruiting | Sponsor: Eli Lilly and Company | Trial primary completion date: May 2028 ➔ May 2029

IO biomarker • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Olomorasib: Primary completion of P3 SUNRAY02 trial (NCT06890598) for resected or unresectable KRAS G12C-mutant NSCLC in May 2029 (Eli Lilly) - Q1 2025 Results: Completion of P3 SUNRAY02 trial for resected or unresectable KRAS G12C-mutant NSCLC in Feb 2032; Primary completion and completion of P1/2 trial (NCT04956640) for NSCLC in Apr 2027

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology