olomorasib (LY3537982) / Eli Lilly - LARVOL DELTA

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

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 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

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 Olomorasib (LY3537982) in Healthy Japanese Participants (clinicaltrials.gov) - P1 | N=191 | Completed | Sponsor: Eli Lilly and Company | Recruiting ➔ Completed

Trial completion

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

Pan-tumor activity of olomorasib (LY3537982), a second-generation KRAS G12C inhibitor (G12Ci), in patients with KRAS G12C-mutant advanced solid tumors. (ASCO 2024) - P1/2, P3 | "Olomorasib demonstrates efficacy across a range of KRAS G12C-mutant solid tumors with a favorable safety profile including in pts with prior G12Ci intolerance. Activity of the second-generation G12Ci olomorasib after prior exposure to G12Ci demonstrates the increased potency and target coverage these agents can deliver compared to first generation inhibitors. Phase 2 expansion is currently enrolling pts with PANC, and a global registrational study investigating olomorasib in combination with pembrolizumab in first-line NSCLC is ongoing (NCT06119581)."

Clinical • Metastases • Pan tumor • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Efficacy and Safety of Olomorasib with Pembrolizumab + Chemotherapy as First-Line Treatment in Patients with KRAS G12C-Mutant Advanced NSCLC (IASLC-WCLC 2024) - P1/2, P3 | "This includes an expansion cohort studying two doses of olomorasib (50mg and 100mg, orally twice daily) combined with standard chemotherapy platinum/pemetrexed and pembrolizumab (all at labeled doses). The ORR was lower in this first-line cohort compared to the prior report with olomorasib combined with pembrolizumab, representative of the higher risk patients with PD-L1-negative status, enrolled to the chemo-immunotherapy backbone. A global, registrational study investigating this combination in first-line NSCLC is currently enrolling (SUNRAY-01, NCT06119581)."

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

Efficacy and safety of olomorasib (LY3537982), a second-generation KRAS G12C inhibitor (G12Ci), in combination with pembrolizumab in patients with KRAS G12C-mutant advanced NSCLC. (ASCO 2024) - P1/2, P3 | "Olomorasib (50 or 100 mg BID) in combination with pembrolizumab demonstrated favorable safety and antitumor activity in pts with KRAS G12C-mutant advanced NSCLC, supporting further development in first-line NSCLC. A global, registrational study investigating this combination in first-line NSCLC is currently enrolling (SUNRAY-01, NCT06119581)."

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

Efficacy and safety of olomorasib (LY3537982), a second-generation KRAS G12C inhibitor (G12Ci), in combination with pembrolizumab in patients with KRAS G12C-mutant advanced NSCLC. (ASCOBT 2024) - P1/2, P3 | "Olomorasib (50 or 100 mg BID) in combination with pembrolizumab demonstrated favorable safety and antitumor activity in pts with KRAS G12C-mutant advanced NSCLC, supporting further development in first-line NSCLC. A global, registrational study investigating this combination in first-line NSCLC is currently enrolling (SUNRAY-01, NCT06119581)."

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

SUNRAY-01, a pivotal, global study of olomorasib (LY3537982) in combination with pembrolizumab with or without chemotherapy for 1L treatment in KRAS G12C-mutant advanced NSCLC. (ASCO 2024) - P3 | "In the open-label randomized dose optimization (pembrolizumab plus olomorasib 50 mg vs 100 mg BID) and single arm safety lead-in (olomorasib plus pembrolizumab, pemetrexed, platinum), the optimal dose of olomorasib for combination therapy will be determined before the phase 3 study (parts A and B) is opened for enrollment. 1 Murciano-Goroff et al. 2023 Cancer Res 83 (8 Suppl): CT028."

Clinical • Combination therapy • IO biomarker • Metastases • Cardiovascular • Gastrointestinal Disorder • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • KRAS • PD-L1

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

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

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

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

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

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