olomorasib (LY3537982) / Eli Lilly - LARVOL DELTA

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

Efficacy and safety of olomorasib, a second-generation KRAS G12C inhibitor, plus cetuximab in KRAS G12C-mutant advanced colorectal cancer. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT04956640 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • 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

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 | "Clinical Trial Registration Number: NCT04956640 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

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

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

Impact of food on the pharmacokinetics of olomorasib in healthy participants (AACR 2025) - P1, P3 | "Food intake does not have a clinically relevant impact on the olomarasib PK as its Cmax and AUC(0-inf) with both meal conditions are within the inter-subject variability in exposure. Olomorasib can safely be taken with or without food, one of several patient-centered design features incorporated into the ongoing registrational SUNRAY-01 trial."

Clinical • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

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 | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • 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: Jilin Cancer Hospital; Jilin Cancer Hospital

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

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 | Not yet recruiting | Sponsor: Eli Lilly and Company

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

Enhancing enrollment to 1L NSCLC trials by allowing 1 prior cycle of standard of care (SOC): SUNRAY-01 experience (ELCC 2025) - P1/2 | "Reasons for receiving 1 cycle of SOC prior to enrollment were studied in the Dose Optimization (DO, olomorasib+pembrolizumab) and Safety Lead-In (SLI, olomorasib+pembrolizumab, pemetrexed, platinum) parts of SUNRAY-01. In the real-world NSCLC cohorts, ~80% of pts received molecular testing results by the 1L start date (Table); an additional ~15% of pts received KRAS results within 21 days of 1L start. Data suggests allowing 1 cycle of SOC therapy prior to enrollment to 1L NSCLC trials of precision therapies could expand the potential enrollable population by permitting time for molecular result return and may enroll a more representative patient population. Initial experience of this approach in SUNRAY-01 reveals adoption by ~25% of pts. This expanded eligibility continues in the phase III parts of SUNRAY-01."

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

KEYNOTE E27: Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C) (clinicaltrials.gov) - P1/2 | N=540 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Jun 2026 ➔ Apr 2027 | Trial primary completion date: Jun 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Biliary Cancer • Colorectal Cancer • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • KRAS

Efficacy and Safety of Olomorasib with Pembrolizumab+Chemotherapy: 1L Treatment in Patients with KRAS G12C-Mutant NSCLC (JSMO 2025) - No abstract available

Clinical • 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 2024 Results: Completion of P3 SUNRAY01 trial for NSCLC in Oct 2029; Primary completion and completion of P1/2 trial (NCT04956640) for NSCLC in Jun 2026

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

A Study of Olomorasib (LY3537982) in Participants With Hepatic Impairment and Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis C • Hepatology • Liver Failure

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 (COSA 2024) - P1/2, P3 | "Olomorasib (50/100mg BID) + pembrolizumab demonstrated favorable safety and antitumor activity in KRAS G12C-mutant advanced NSCLC. A global, registrational study investigating this combination in first-line NSCLC is currently enrolling (SUNRAY-01/NCT06119581)."

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

A Study of LY3537982 in Chinese Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Jan 2026 ➔ Apr 2027 | Trial primary completion date: Jan 2025 ➔ Apr 2026

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

A Study of Olomorasib (LY3537982) in Participants With Hepatic Impairment and Healthy Participants (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial • Hepatitis C • Hepatology • Liver Failure

A Study of LY3537982 in Chinese Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • 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

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. (ASCOBT 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. 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

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

Olomorasib Plus Pembrolizumab Generates Antitumor Activity in KRAS G12C+ NSCLC (OncLive) - "P1/2 | N=550 | NCT04956640 | Sponsor: Eli Lilly and Company | "In efficacy evaluable patients with metastatic disease being treated in the first line (n = 17), the objective response rate (ORR) with the combination was 77% and was composed entirely of partial responses (PR). The best responses to treatment included stable disease (SD; 12%) and progressive disease (PD; 6%), although 6% of patients were not evaluable (NE). At a median follow-up of 5.5 months, the median progression-free survival (PFS) was NE (95% CI, 3.6-NE). The estimated 6- and 12-month PFS rates were both 72.8%....The median PFS was 8.1 months (95% CI: 5.6-15.6). Notably, preliminary CNS activity was seen, with CNS responses observed in patients with NSCLC and measurable brain metastases."

P1/2 data • Non Small Cell Lung Cancer

KEYNOTE E27: Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C) (clinicaltrials.gov) - P1/2 | N=550 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Feb 2026 ➔ Jun 2026 | Trial primary completion date: Feb 2026 ➔ Jun 2026

Metastases • Trial completion date • Trial primary completion date • Biliary Cancer • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • KRAS

A Drug-Drug Interaction Study of LY3537982 on Midazolam, Digoxin, and Rosuvastatin in Healthy Participants (clinicaltrials.gov) - P1 | N=35 | Completed | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Completed | N=56 ➔ 35

Enrollment change • Trial completion