olomorasib (LY3537982) / Eli Lilly - LARVOL DELTA

First-line (1L) Olomorasib + Chemoimmunotherapy (Chemo-IO) in KRAS G12C-Mutant NSCLC: Updated Results from the LOXO-RAS-20001 and SUNRAY-01 Trials (ESMO 2026) - No abstract available

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

First-line (1L) Olomorasib + Pembrolizumab in KRAS G12C-Mutant NSCLC: Updated Results from LOXO-RAS-20001 and SUNRAY-01 (ESMO 2026) - No abstract available

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

A Study Comparing Two Ways of Taking Olomorasib (LY3537982) in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open

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

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

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

First-line (1L) olomorasib + pembrolizumab in patients with KRAS G12C–mutant advanced NSCLC, and PD-L1 expression 0-49%, from the dose optimization cohorts of LOXO-RAS-20001 and SUNRAY-01. (ASCO 2026) - P1/2, P3 | "Olomorasib + pembrolizumab demonstrated promising efficacy in pts with 1L KRAS G12C-mutant advanced NSCLC, and PD-L1 expression <1% and 1-49% with ORRs that compare favorably with historical outcomes for pembrolizumab and chemo-immunotherapy in unselected advanced NSCLC. Olomorasib + pembrolizumab is under evaluation in pts with 1L KRAS G12C-mutant metastatic NSCLC (SUNRAY-01, NCT06119581) and early-stage NSCLC (SUNRAY-02, NCT06890598). Response and time-to-event endpoints in the Efficacy evaluable population with PD-L1 0-49% (N=30*)."

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

1L olomorasib plus pembrolizumab +/- chemotherapy in KRAS G12C-mutant NSCLC patients +/- a prior cycle of SOC: Results from LOXO-RAS 20001 and SUNRAY-01. (ASCO 2026) - P1/2, P3 | "One cycle of SOC prior to enrollment was permitted when timely initiation of treatment was clinically indicated, this included pembrolizumab (doublet) and pemetrexed + platinum +/- pembrolizumab, or pembrolizumab alone (quad). Treatment with 1 cycle of SOC prior to enrollment appeared to have no detrimental effect on safety and efficacy outcomes of olomorasib in combination with pembrolizumab +/- chemotherapy in pts with KRAS G12C NSCLC. This is the first analysis of the clinical impact of 1 prior cycle of SOC in a NSCLC clinical trial, allowing early access to treatment if clinically indicated. Implementation of this strategy in SUNRAY-01 and other 1L NSCLC trials may expand enrollment and allow for a more representative pt population."

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

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

A Study of Olomorasib (LY3537982) in Participants With Advanced Colorectal Cancer and a KRAS G12C Mutation (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P2 trial • Colorectal Cancer • Oncology • 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 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

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

Nursing Management of KRAS G12C Inhibitor Toxicities in Thoracic Malignancy: A Canadian Perspective (IASLC-WCLC 2026) - "Unlike cell-surface receptor targeting-tyrosine kinase inhibitors (TKIs), such as osimertinib and alectinib, which are familiar to thoracic oncology nurses, KRAS G12C inhibitors act upon an intracellular downstream signaling pathway...While first-in-class inhibitors sotorasib and adagrasib are approved, next-generation agents including divarasib, olomorasib, and calderasib are demonstrating more favourable safety profiles in ongoing trials...As KRAS G12C inhibitors expand beyond NSCLC to broader solid tumour indications, proactive, evidence-informed, and standardized nursing management is essential to optimizing patient outcomes and ensuring equitable access to precision oncology care globally. This requires that nurses be equipped with the education and clinical tools for informed, evidence-based symptom management across geographically diverse healthcare systems."

Hepatology • Interstitial Lung Disease • Liver Failure • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Thoracic Cancer • KRAS

KRAS-Targeted Therapies in NSCLC: Resistance, Combination Strategies, and Emerging Clinical Paradigms. (PubMed, Med Oncol) - "Sotorasib and adagrasib achieve ORRs of 37-43% and median PFS ~ 6-7 months in previously treated KRAS G12C NSCLC, with improved tolerability over docetaxel. Next-generation inhibitors (olomorasib, divarasib, glecirasib, D-1553, IBI351) demonstrate ORRs 45-55% and, in some studies, PFS exceeding first-generation agents, while emerging KRAS G12D inhibitors show early proof-of-concept activity...KRAS-mutant NSCLC is transitioning from historically untargetable disease to a therapeutically actionable subset. Future progress hinges on resistance-directed combinations, biomarker-guided personalization, expansion to non-G12C mutants, and evaluation in earlier disease settings."

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

A Study Comparing Two Ways of Taking Olomorasib (LY3537982) in Healthy Participants (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

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

Olomorasib + Pembrolizumab KRAS G12C Mutant, PD-L1 TPS 1-49% Locally Advanced or Metastatic NSCLC (clinicaltrials.gov) - P2 | N=60 | Suspended | Sponsor: UNC Lineberger Comprehensive Cancer Center | Initiation date: Jun 2026 ➔ Oct 2026 | Not yet recruiting ➔ Suspended

IO biomarker • Trial initiation date • Trial suspension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

SUNRAY-02: A Phase 3 Study of Olomorasib and Immunotherapy in Stage II-III KRAS G12C-Mutant NSCLC (DKK 2026) - "The phase 1/2 LOXORAS-20001 study showed that olomorasib alone and with pembrolizumab (pembro) demonstrated efficacy and a favorable safety profile in patients with advanced NSCLC.SUNRAY-02 is a global, randomized, phase 3 study that aims to determine the efficacy of olomorasib with standard of care immunotherapy following definitive treatment (tx) of stage IIIII NSCLC.Eligible participants are ≥18 years, ECOG PS 0-1, with pathological confirmation of NSCLC with known KRAS G12C mutation and PD-L1 expression (0-100%)...Part B participants will be randomized 1:1 to receive either olomorasib+durvalumab or pbo+durvalumab. Primary endpoint: progression-free survival by blinded independent central review. All participants will receive combination tx for up to ~1 year, followed by olomorasib or pbo monotherapy to complete up to 3 years of total tx.Previously presented at WCLC 2025Sponsored by Eli Lilly and Company."

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

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

Olomorasib and immunotherapy in stage II-III KRAS G12C-mutant NSCLC after definitive therapy: SUNRAY-02 study rationale (ELCC 2026) - P3 | "Part A pts with resected NSCLC receive olomorasib or PBO in combination with pembro, while Part B pts with unresectable (UR) NSCLC receive olomorasib or PBO in combination with durvalumab (durva). RWD also show that approximately 60% pts with UR NSCLC receive concurrent chemoradiotherapy followed by durva. Olomorasib combined with IO may provide additional clinical benefit for these pts."

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

KRAS G12C-Targeted Therapy in Non-Small Cell Lung Cancer: From Resistant Salvage to Potential First-Line Backbone. (PubMed, Int J Mol Sci) - "The discovery of a cryptic binding pocket accessible in the GDP-bound state enabled covalent inhibitors-sotorasib and adagrasib-that have received regulatory approval for previously treated KRAS G12C-mutant NSCLC, with sotorasib demonstrating PFS and OS superiority over docetaxel in CodeBreaK 200 and adagrasib showing meaningful intracranial activity and a progression-free survival benefit over docetaxel in KRYSTAL-12...Next-generation covalent inhibitors (divarasib, glecirasib, olomorasib), tri-complex RAS(ON) inhibitors (RMC-6291), pan-KRAS agents, and rationally designed combinations with EGFR, SHP2, SOS1, and PD-1 inhibitors are repositioning KRAS-directed therapy toward earlier lines of treatment. This review integrates the structural, signaling, and clinical biology of KRAS G12C with contemporary trial and real-world evidence to examine the emerging case for first-line KRAS G12C inhibition in genomically defined subsets of NSCLC. First-line use nonetheless remains..."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • KEAP1 • KRAS • STK11 • TP53