Eli Lilly olomorasib ESMO 2026 data presented in Madrid, Spain, show durable first-line activity for the investigational KRAS G12C inhibitor in non-small cell lung cancer (NSCLC), according to an Oct. 25, 2026 announcement from Eli Lilly and Company (NYSE: LLY).
The results come from a poster presentation of the Phase 1/2 LOXO-RAS-20001 trial and the safety lead-in portion of the Phase 3 SUNRAY-01 trial. A separate rapid oral presentation was also given at the European Society for Medical Oncology (ESMO) Congress. Lilly describes olomorasib as an investigational, next-generation oral KRAS G12C inhibitor. The data cover first-line patients with advanced KRAS G12C-mutant NSCLC.
In the cohort receiving Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) without chemotherapy, median progression-free survival (PFS) and duration of response (DOR) had not been reached after a median follow-up of nearly 21 months. In the chemoimmunotherapy cohort, Lilly reported an investigator-assessed overall response rate (ORR) of 62% and a median DOR of 14.5 months. Lilly expects first randomized Phase 3 data from SUNRAY-01 in the first half of 2027. That is a forward-looking expectation and not a guarantee.
Lilly olomorasib ESMO 2026 Poster Results: Olomorasib Plus Pembrolizumab Without Chemotherapy
The poster analysis in the Lilly olomorasib ESMO 2026 package included 85 patients receiving olomorasib plus pembrolizumab as first-line treatment. Lilly reported that 64% of these patients had PD-L1 expression of 50% or higher. Median DOR and median PFS were not yet reached after a median follow-up of 20.7 months, in both the overall population and the PD-L1 50% or higher subgroup.
At 18 months, the PFS rate was 55% in the overall population and 65% in patients with PD-L1 expression of 50% or higher. Lilly characterized the activity as durable across all PD-L1 expression levels. The company did not disclose an ORR for this cohort in the announcement.
Lilly said the safety profile was consistent with earlier reports and with the known profiles of each medicine. The most common Grade 3 or higher treatment-related adverse events (TRAEs) were increased ALT (15.3%), increased AST (12.9%), and diarrhea (8.2%). TRAEs led to olomorasib dose reduction in 31.8% of patients and discontinuation of the regimen in 11.8%. No Grade 5 TRAEs occurred, and the protocol does not require prophylactic medications for olomorasib.
| Parameter | Olomorasib + Pembrolizumab (No Chemotherapy) |
|---|---|
| Trial source | LOXO-RAS-20001 (Phase 1/2) and SUNRAY-01 safety lead-in (Phase 3) |
| Patients (n) | 85 |
| Setting | First-line KRAS G12C-mutant NSCLC |
| PD-L1 ≥50% | 64% of patients |
| Median follow-up | 20.7 months |
| Median PFS | Not reached |
| Median DOR | Not reached |
| 18-month PFS rate, overall | 55% |
| 18-month PFS rate, PD-L1 ≥50% | 65% |
| ORR | Not disclosed |
Lilly olomorasib ESMO 2026 Rapid Oral Presentation: Olomorasib Plus Chemoimmunotherapy
The second Lilly olomorasib ESMO 2026 analysis was a single-arm study of olomorasib plus pembrolizumab, pemetrexed and platinum chemotherapy. It included 77 patients with a median follow-up of 18.7 months, which Lilly said adds nine months over the earlier analysis. Most patients (74%) had PD-L1 expression below 50%.
The investigator-assessed confirmed ORR was 62% (48/77). Median DOR was 14.5 months (95% CI, 8.5-not estimable), and median PFS was 11.6 months (95% CI, 9.5-21.5). Dr. Marcelo V. Negrao of The University of Texas MD Anderson Cancer Center, the presenting author, said responses lasting more than a year across PD-L1 levels support continued study of the combination.
The most common Grade 3 or higher TRAEs were neutropenia (21%), anemia (17%), increased alanine aminotransferase (12%) and thrombocytopenia (12%). TRAEs led to olomorasib dose reduction in 19.5% of patients and discontinuation of the regimen in 7.8%. No Grade 5 TRAEs occurred, and no prophylactic medications for olomorasib are required by the protocol.
| Parameter | Olomorasib + Chemoimmunotherapy |
|---|---|
| Regimen | Olomorasib + pembrolizumab + pemetrexed + platinum chemotherapy |
| Patients (n) | 77 |
| PD-L1 <50% | 74% of patients |
| Median follow-up | 18.7 months |
| Confirmed ORR (investigator-assessed) | 62% (48/77) |
| Median DOR | 14.5 months (95% CI, 8.5-NE) |
| Median PFS | 11.6 months (95% CI, 9.5-21.5) |
| Dose reduction of olomorasib | 19.5% |
| Treatment discontinuation | 7.8% |
| Grade 5 TRAEs | None |
| Grade 3 or Higher TRAE | Olomorasib + Pembrolizumab (n=85) | Olomorasib + Chemoimmunotherapy (n=77) |
|---|---|---|
| Increased ALT | 15.3% | 12% |
| Increased AST | 12.9% | Not disclosed |
| Diarrhea | 8.2% | Not disclosed |
| Neutropenia | Not disclosed | 21% |
| Anemia | Not disclosed | 17% |
| Thrombocytopenia | Not disclosed | 12% |
How Lilly olomorasib ESMO 2026 Findings Support the SUNRAY-01 Phase 3 Program
Lilly links the Lilly olomorasib ESMO 2026 analyses to the ongoing Phase 3 SUNRAY-01 study (NCT06119581). SUNRAY-01 is a global master protocol containing two randomized Phase 3 trials. Part A is a randomized, double-blind, placebo-controlled evaluation of olomorasib plus pembrolizumab versus placebo plus pembrolizumab in patients with PD-L1 expression of 50% or higher.
Part B compares olomorasib plus chemoimmunotherapy with placebo plus chemoimmunotherapy regardless of PD-L1 expression, and it has completed enrollment. Part C is designed to assess olomorasib plus pembrolizumab in patients with PD-L1 expression below 50%. The broader program also includes the Phase 3 SUNRAY-02 trial (NCT06890598) in resectable and unresectable non-metastatic disease. A third study, NCT04956640, covers olomorasib as monotherapy and in combinations in other advanced solid tumors.
Olomorasib remains investigational and is not approved by the FDA or any other regulatory authority for any use. Lilly states that the FDA has granted two Breakthrough Therapy designations. One is for olomorasib with pembrolizumab in first-line KRAS G12C-mutant NSCLC with PD-L1 expression of 50% or higher. The other is for olomorasib alone in previously treated KRAS G12C-mutant advanced pancreatic cancer. The designation is meant to expedite development and review, and it does not mean a medicine is approved.
| Trial | Identifier | Design and Population | Status per Lilly |
|---|---|---|---|
| SUNRAY-01 Part A | NCT06119581 | Olomorasib + pembrolizumab vs placebo + pembrolizumab; PD-L1 ≥50% | Ongoing |
| SUNRAY-01 Part B | NCT06119581 | Olomorasib + chemoimmunotherapy vs placebo + chemoimmunotherapy; any PD-L1 | Enrollment completed |
| SUNRAY-01 Part C | NCT06119581 | Olomorasib + pembrolizumab; PD-L1 <50% | Designed to assess; status not detailed |
| SUNRAY-02 | NCT06890598 | Phase 3; resectable and unresectable non-metastatic NSCLC | Ongoing |
| LOXO-RAS-20001 | NCT04956640 | Phase 1/2; monotherapy and combinations in advanced solid tumors | Ongoing |
Why Lilly olomorasib ESMO 2026 Data Matter for First-Line KRAS G12C NSCLC Treatment
KRAS G12C mutations occur in approximately 13% of people with NSCLC, the most common form of lung cancer. Lilly notes that there are no approved targeted therapies for first-line treatment of KRAS G12C-mutant NSCLC. The standard of care is immunotherapy with or without chemotherapy, and most patients do not go on to second-line therapy. The company adds that toxicity has been a persistent challenge for some KRAS G12C inhibitor combinations with immunotherapy. This is the context for the Lilly olomorasib ESMO 2026 readout. For background on the disease, see the KRAS review in Nature Medicine cited by Lilly.
Jacob Van Naarden, Executive Vice President and President of Lilly Oncology, said that for many patients “the first line is their only line.” He said the results deepen Lilly’s conviction in olomorasib alongside standard PD-1-based backbone therapy. He also pointed to a tolerability profile that does not require prophylactic medications. Lilly said it is hopeful that pivotal Phase 3 data with chemoimmunotherapy in the first half of 2027 will be a significant moment for the field. That statement is forward-looking.
