olomorasib (LY3537982) / Eli Lilly - LARVOL DELTA

FMC-242, a highly potent and selective covalent inhibitor of the PI3Kα -RAS interaction, demonstrates robust anti-tumor activity as monotherapy and in combination with targeted therapies (AACR 2026) - "Combination of FMC-242 with targeted therapies including EGFR inhibitors, KRASG12C inhibitors such as FMC-376, divarasib, olomorasib, or pan-RAS/KRAS agents results in enhanced efficacy and tumor regressions in vivo. Together, these data demonstrate the potential of FMC-242, a selective covalent inhibitor of PI3Kα -RAS interaction, to deliver improved outcomes for patients as monotherapy and in combination with targeted therapies in the clinic."

Combination therapy • Monotherapy • Oncology • HER-2 • KRAS • PIK3CA

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

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

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 Healthy Participants (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open

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

Olomorasib + Chemoimmunotherapy in KRAS G12C-Mutant NSCLC: Results from LOXO-RAS-20001 and SUNRAY-01 (DKK 2026) - "Here, we report results of 1L patient (pts) from LOXO-RAS-20001 and the safety lead-in for SUNRAY-01.Pts with advanced KRAS G12C-mutant NSCLC, PD-L1 0-100% (ECOG PS 0-1) were assigned to olomorasib (50/100 mg, orally BID) with pembrolizumab+chemotherapy (chemo-IO). These updated findings further support the ongoing SUNRAY-01 trial, comparing olomorasib (100 mg BID)+chemo-IO vs placebo+chemo-IO as 1L tx in pts with KRAS G12C-mutant NSCLC and any PD-L1 level. Previously presented at WCLC 2025Sponsored by Eli Lilly and Company."

IO biomarker • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • 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

Olomorasib+Pembrolizumab in KRAS G12C-Mutant NSCLC: Results from LOXO-RAS-20001 and SUNRAY-01 (DKK 2026) - "These updated findings, including longer follow-up on Phase 1 pts, provide additional support for the ongoing Phase 3 trial, comparing olomorasib (100 mg BID)+pembro vs placebo+pembro as 1L treatment in pts with KRAS G12C-mutant NSCLC and PD-L1 ≥50%. Previously presented at WCLC 2025Sponsored by Eli Lilly and Company ."

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

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

SUNRAY-01: A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=1264 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Oct 2029 ➔ Jan 2031 | Trial primary completion date: Oct 2026 ➔ Nov 2027

IO biomarker • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • 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 | Trial completion date: Nov 2028 ➔ Apr 2029

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PD-L1

Pan-tumor activity of olomorasib, a next-generation KRAS G12C inhibitor in KRAS G12C-mutant advanced solid tumors: a first-in-human study. (PubMed, Nat Commun) - P1/2 | "Intracranial responses were observed in patients with untreated, active brain metastases. This may support the potential of next-generation KRAS G12C inhibitors to overcome limitations of earlier agents and justify further investigation of combination therapy."

First-in-human • Journal • P1 data • Pan tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

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 Systematic Review of the Efficacy of KRAS p.G12C Inhibitors in Metastatic Colorectal Cancer: The Current State of Science. (PubMed, Cancer Invest) - "Adagrasib monotherapy yielded a median PFS of 4.4-5.6 months, an OS of 10-19.8 months, and an ORR of 19-23%, while its combination with cetuximab reported a PFS of 6.9 months, an OS of 13.4-15.9 months and an ORR of 34-46%...When combined with panitumumab, 960 mg sotorasib demonstrated better results with a PFS of 5.6-5.7 months, OS of 15.2 months and an ORR of 12.5-30%. Similarly, divarasib monotherapy led to a PFS of 5.6-6.9 months and an ORR of 20%, while its combination with cetuximab resulted in a PFS of 8.1 months and an ORR of 62.5%. Combination therapy of olomorasib and MK-1084, which are new-generation KRAS p.G12C (c.34G > T) inhibitors, with cetuximab also demonstrated highly promising efficacy with ORR of 38-44% and 50%, respectively...Initial results of KRAS-G12C inhibitors appear highly promising when they are combined with anti-EGFR therapy compared to historical therapeutic agents indicated for patients with chemotherapy-refractory CRC. Encouraging..."

Journal • Colorectal Cancer • Oncology • Solid Tumor • KRAS

A Study of Olomorasib (LY3537982) in Healthy Participants (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

Therapeutic advances with KRASG12C inhibitors and combination strategies in non-small cell lung cancer brain metastases. (PubMed, Cancer Gene Ther) - "This article examines the clinical and translational application of specific next-generation blood-brain barrier penetrant KRASG12C inhibitors, such as sotorasib, adagrasib, olomorasib, RMC-6236, and D3S-001, and their rational integration with radiation therapy, targeted therapies, and immunotherapies to overcome therapeutic resistance in patients with NSCLC brain metastases. This review summarizes recent advances aimed at enhancing intracranial tumor control and overall survival in patients with NSCLC brain metastases through the use of next-generation KRASG12C inhibitors and multimodal therapies."

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

Olomorasib: Primary completion of P3 SUNRAY01 trial (NCT06119581) for NSCLC in Oct 2026 (Eli Lilly) - Q4 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

Olomorasib: Primary completion and completion of P1/2 trial (NCT04956640) for KRAS G12C-mutant advanced solid tumors in Apr 2027 (Eli Lilly) - Q4 2025 Results

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

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

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

Trial completion