Greywolf’s Oral ERAP1 Inhibitor Shows 13–36% Response Rates in Hard-to-Treat Cancers at ASCO 2026

The highest objective response rate (ORR) was seen in urothelial carcinoma at 36%, with 5 of approximately 14 evaluable patients achieving a confirmed partial response . Non-small cell lung cancer (NSCLC) patients showed a 21% ORR (3 of 14 evaluable patients) . Microsatellite-stable colorectal cancer (MSS-CRC) without liver metastases—a notoriously immunotherapy-resistant population—produced an ORR of roughly 17%, with 2 of roughly 12 evaluable patients responding .

Partial responses were also documented in hepatocellular carcinoma (2 patients), cervical cancer (2 patients), and head and neck squamous cell carcinoma (1 patient), though evaluable-patient denominators were not reported for these cohorts .

It is important to view these numbers in context. This was an open-label, single-arm Phase 1b expansion study without a randomized comparator, so it cannot definitively separate the effect of GRWD5769 from a possible PD-1 rechallenge effect or patient selection bias . Nevertheless, the consistency of response signals across several difficult-to-treat tumor types has drawn attention.

Durable clinical benefit—defined as progression-free survival beyond six months—was also reported. At the time of data cutoff, the rate of durable clinical benefit was 55% for NSCLC, 51% for MSS-CRC, 38% for head and neck squamous cell carcinoma, 36% for urothelial carcinoma, 32% for hepatocellular carcinoma, and 18% for cervical cancer . These numbers describe the proportion of patients whose disease remained controlled for at least six months, not just the proportion whose tumors shrank. In the MSS-CRC cohort, where checkpoint inhibitors usually deliver single-digit response rates, a six-month disease control rate above 50% is encouraging.

On the safety side, GRWD5769 with cemiplimab was well tolerated across all cohorts. "No safety concerns" were reported, and there were no new safety signals that would halt development, according to the company . Earlier data from the monotherapy dose-escalation phase, published in 2024, also showed a clean safety profile, with no treatment-related serious adverse reactions, no immune-related adverse events, and no dose-limiting toxicities across the doses tested .

GRWD5769 is a first-in-class oral inhibitor of Endoplasmic Reticulum Aminopeptidase 1 (ERAP1), an enzyme that trims peptide antigens inside the endoplasmic reticulum before they are loaded onto MHC class I molecules for presentation on the cell surface . By inhibiting ERAP1, the drug alters the repertoire of antigens displayed by tumor cells, effectively changing the “flag” they wave at patrolling T-cells. The hypothesis is that this altered antigen landscape can reawaken an immune response that had grown tolerant to the original tumor signature, especially when combined with a checkpoint inhibitor like cemiplimab that takes the brakes off T-cells .

Greywolf previously demonstrated proof-of-mechanism at ASCO 2024, showing dose-dependent modulation of the immunopeptidome in cancer patients—the first time the human immunopeptidome had been pharmacologically manipulated with therapeutic intent . The 2026 data extends that pharmacodynamic evidence into actual clinical responses.

The EMITT-1 trial remains ongoing as a modular, multi-part Phase 1/2 study evaluating GRWD5769 alone and in combination with cemiplimab across multiple solid tumor types. Trial sites are active in Australia, Spain, and the UK . Based on these Phase 1b results, the company plans to continue development in patients with secondary anti-PD-1 resistance and MSS colorectal cancer, two populations where the unmet need is acute and the early signal is promising .