olomorasib (LY3537982) / Eli Lilly - LARVOL DELTA

Efficacy and Safety of Olomorasib in Combination with Pembrolizumab in Treatment of Patients with KRAS G12C-Mutant Advanced NSCLC. (PubMed, J Thorac Oncol) - "Olomorasib + pembrolizumab demonstrated manageable safety and promising antitumor activity in patients with KRAS G12C-mutant advanced NSCLC across PD-L1 expression levels, especially in the high PD-L1 first-line setting."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

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

Enrollment open

KaRAnaSa: A Study of Amivantamab and Olomorasib Combination Therapy in Participants With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=60 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Phase 3, Multicenter, Double-Blind, Placebo-controlled Study Assessing the Efficacy and Safety of Olomorasib in Combination with Standard of Care Immunotherapy in Participants with Resected or Unresectable KRAS G12C-Mutant, Non-Small Cell Lung Cancer - SUNRAY-02 (ChiCTR) - P3 | N=700 | Not yet recruiting | Sponsor: Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

IO biomarker • New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

Transcription factors enhancing anti-tumor chemokine expression and lymphocyte infiltration in KRAS G12C inhibitor-resistant non-small cell lung cancer. (AACR-NCI-EORTC 2025) - "Supporting this, early-phase clinical trials combining adagrasib or olomorasib with pembrolizumab have reported improved efficacy, with ORRs ranging from 63–75% (Garassino et al., Ann. These results suggest that G12Ci may stimulate CXCL chemokine expression either by activating transcription or by relieving repression by specific TFs, which may drive lymphocyte recruitment and help convert 'immune cold' tumors into 'hot' microenvironments. The transcription factors we identified may represent new therapeutic targets to potentiate anti-tumor chemokine signaling and improve responses to immunotherapy."

IO biomarker • Colorectal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CXCL10 • CXCL11 • CXCL9 • FOXP1 • IRF1 • KRAS • PD-L1 • STING • STK11 • ZNF384

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

Enrollment open • Nephrology • Renal Disease

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) - P1/2, P3 | "These results support continued clinical development of olomorasib in pts with KRAS G12C-mutant NSCLC including in pts with brain mets. Two global registrational studies investigating olomorasib in combination with immunotherapy in first-line metastatic and early-stage NSCLC are ongoing (NCT06119581, NCT06890598)."

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

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

Enrollment open

Olomorasib (investigational KRAS G12C inhibitor) (PRNewswire) - "In a mini oral presentation, Lilly will share results from the Phase 1/2 study on the intracranial efficacy of olomorasib, a next-generation KRAS G12C inhibitor, in patients with KRAS G12C-mutant non-small cell lung cancer (NSCLC) who have active, untreated brain metastases."

P1/2 data • Non Small Cell Lung Cancer

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