A phase 2 trial combining Agenus’ and MiNK Therapeutics’ cancer candidates has missed its primary endpoint. But with the study generating early evidence the cocktail improves survival, the biotechs said the data support further assessment of the combination.
Investigators at Memorial Sloan Kettering Cancer Center initiated the trial in advanced gastroesophageal cancer patients failed by PD-1 drugs. Participants received a CTLA-4 inhibitor and an anti-PD-1 antibody—Agenus’ botensilimab and balstilimab, respectively—and MiNK’s invariant natural killer T cell candidate agenT-797. Ramucirumab, which Eli Lilly sells as Cyramza, and the chemotherapy paclitaxel were also part of the cocktail.
The study missed its primary endpoint, with none of the 15 patients with measurable disease having a partial or complete response. Eleven patients had stable disease and the other four progressed on the treatment regimen, while response data were unavailable for two participants, according to Agenus’ April 17 release.
Agenus and MiNK argued that durability and survival are the most relevant measures of clinical benefit. Five patients received agenT-797, botensilimab and balstilimab as an induction therapy before starting ramucirumab and paclitaxel. Two people only received agenT-797 as an induction therapy. The other 10 participants started all the treatments at the same time.
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Median progression-free survival (PFS) was 6.9 months in participants who received induction therapy, compared to 3.5 months in their counterparts who started the treatments simultaneously. Agenus and MiNK said the data show the potential importance of immune priming and treatment sequencing. Lilly previously reported a median PFS of 4.4 months in a phase 3 trial of ramucirumab and paclitaxel.
Agenus and MiNK reported median overall survival (OS) of 9.5 months in the induction cohort, compared to 5.2 months in the other 10 patients. At Month 18, 43% of patients in the induction group were alive, compared to 0% of people in the simultaneous treatment arm. Lilly reported a median OS of 9.6 months in its own phase 3 study.
The biotechs said disease control and survival results seen in a subset of patients support further study of their approach. For both drug developers, gastroesophageal cancer is part of a broader set of target indications.
MiNK, which spun out of Agenus in 2021, is testing agenT-797 in multiple diseases, including conditions beyond cancer such as severe acute lung injury. Agenus is preparing to file for approval of botensilimab and balstilimab in colorectal cancer while working to validate the combination in a phase 3 trial.
