An investigational cocktail was tied to a 0% overall response rate in patients with gastroesophageal cancer, but developers Agenus and MiNK Therapeutics aren’t giving up on the program just yet.
A cancer cocktail in development by Agenus and its spinout MiNK Therapeutics failed to elicit an overall response in a Phase 2 study, though the companies say other survival findings support continued efforts.
The biotechs were hoping the combination of Agenus’ two experimental immunotherapies botensilimab (BOT) and balstilimab (BAL), plus MiNK’s allogeneic cell therapy agenT-797, would improve overall response rate (ORR) for patients with gastroesophageal adenocarcinoma. The approved VEGFR2 antagonist Cyramza and chemotherapy were also added to the treatment regimen.
However, the investigational cocktail failed to elicit any complete or partial response among 15 eligible patients, according to an efficacy analysis set to be shared Monday afternoon at the American Association for Cancer Research (AACR) Annual Meeting. Patients included in the findings were diagnosed with advanced disease that has not responded to PD-1 treatment.
A previous Phase 3 trial showed that second-line treatment with Cyramza and chemotherapy was tied to an ORR of 28% and median progression free survival (PFS) of 4.4 months.
While the Agenus-MiNK candidate missed the trial’s primary goal, the biotechs pointed elsewhere to a 73% stable disease rate. Three patients also saw overall survival of more than 20 months, including one who has remained progression free after more than 22 months.
The companies also zeroed in on results from a subpopulation of patients receiving an induction cycle of the cocktail. Those patients had a PFS of 6.9 months compared to 3.5 months for the 10 patients who started all the therapies together.
The induction strategy was also tied to higher survival rates at 12 and 18 months, findings the companies say signal immune activation and tumor reprogramming.
Based on the subset data, Agenus and MiNK believe durability and survival “may be the most clinically relevant endpoints” in this specific patient population, according to the companies’ release shared on Friday. The subset findings “support further study of this approach,” they said.
As for safety, all patients experienced an adverse event (AE). Of 17 total patients, 53% experienced events of grade 3 or higher. The partners did not share further details on potential grade 4 and 5 events.
The safety data are “consistent with the component agents,” the companies said, adding that the most frequent treatment-emergent adverse events were fatigue, fever and diarrhea. Nine patients (53%) experienced an immune-related AE, with four of those events classified as grade 3 or higher events.
Agenus has been assessing its anti-CTLA-4 antibody BOT and PD-1 blocker BAL across several cancer types. The biotech recently launched a Phase 3 trial for the investigational combo in metastatic colorectal cancer and is prepping for potential future regulatory submissions in the U.S. and Europe.
In 2021, the Massachusetts-based biotech spun out its invariant natural killer T (iNKT) cell therapy agenT-797, creating MiNK. MiNK is testing agenT-797 in several indications, including a midstage study in severe acute lung injury. The New York spinout also touts a tech platform to develop other iNKT candidates and has several other programs in earlier-stage development.
