Vopratelimab/JTX-4014 to be Evaluated in Phase 2 Study for Immunotherapy-Naïve NSCLC

Jounce Therapeutics will evaluate its lead agent vopratelimab in combination with the anti–PD-1 monoclonal antibody JTX-4014, in patients with non-small cell lung cancer (NSCLC) who have not received immunotherapy.

The clinical-stage immunotherapy company is still working to recover from a recent setback with vopratelimab in this disease. The company announced on November 3, 2020, that enrollment to the EMERGE trial exploring vopratelimab plus ipilimumab (Yervoy) (NCT03989362) would be halted.¹

Vopratelimab, is a monoclonal antibody that binds to and activates ICOS, a protein on the surface of certain T cells that may stimulate an immune response against tumor cells.

Investigators reviewing preliminary results from the phase 2 trial determined the combination was unlikely to succeed. Only 1 patient displayed an objective response and only 9 of 50 patients in the trial remain on treatment.

“We are disappointed that an early look at the EMERGE data indicates that we will not meet our pre-specified interim criteria for continued enrollment,” Jounce chief medical officer Beth Trehu, MD, said in a statement.

The company is proceeding with the phase 2 SELECT trial (NCT04549025), which began enrollment in October. The trial (N = 75) compares the safety and efficacy of vopratelimab plus JTX-4014 versus JTX-4014 alone in patients with NSCLC who are positive for the TISvopra predictive biomarker. Eligible patients may have not received therapy with a PD-1/PD-L1 inhibitor and have progressed on a platinum-based chemotherapy regimen.

The primary endpoint is mean percent change from baseline in all measurable lesions. Secondary endpoints include progression-free survival (PFS), objective response, median duration of response, and median overall survival (OS).

Investigators expect to have preliminary efficacy data from SELECT in 2021.

TISvopra is an 18-gene RNA tumor inflammation signature optimized to predict the emergence of ICOS-high CD4 T cells. Investigators will screen patients in SELECT for the TISvopra biomarker. Jounce estimates that approximately 20% of patients in the trial will be months above the TISvopra threshold and potentially eligible for the trial.

Patients were classified based on tumor inflammation score (TIS) and investigators established a TIS threshold that optimized the predictive emergence of ICOS-high CD4 cells in the presence of vopratelimab. They then applied this threshold to clinical data assessing clinical benefit. 

Jounce is moving ahead with SELECT based in part on results from the phase 1/2 ICONIC trial (NCT02904226).

Among patients who were positive for TISvopra (n = 22) in ICONIC, the median PFS was 2.2 months (95% CI, 2.0-4.6) compared with 1.9 months (95% CI, 1.8-2.0) for those who were negative for TISvopra (n = 67). PFS rate strongly favored the TISvopra-positive group at 6 months (20.1% vs 3.7%) and 9 months (20.1% vs 0%).²

The median OS among the TISvopra-positive cohort was 16.9 months versus 6.2 months among the negative cohort (P = .0062).

In a retrospective subset analysis, investigators found that positive for TISvopra score improved RECIST response and was predictive for emergence of an ICOS high CD4 T cell population in patients treated with vopratelimab. In contrast, PD-L1 stats was not predictive for clinical benefit.

References

1. Jounce Therapeutics Announces Update on Vopratelimab Program. News release. Accessed December 3, 2020. bit.ly/3ol7Pjw
2. Yap TA, Gainor JF, Burris HA et. al. Association of a predictive RNA signature (RS) with emergence of ICOS hi CD4 T cells and efficacy outcomes for the ICOS agonist vopratelimab (vopra) and nivolumab (nivo) in patients (pts) on the ICONIC trial. J Clin Oncol. 2020;38(suppl 5; abstr 14). Abst 14.