Jounce Falls on Missed Endpoint in Phase II NSCLC Study

Clinical Trials Failure

Jounce Therapeutics fell more than 15% Wednesday morning after announcing that its Phase II SELECT trial assessing a combination treatment for non-small cell lung cancer failed to meet its primary endpoint

The mid-stage study was assessing vopratelimab (vopra), Jounce's inducible costimulator (ICOS) agonist in combination with checkpoint inhibitor pimivalimab (pimi) compared to pimivalimab monotherapy in immunotherapy naïve, TISvopra biomarker-selected NSCLC patients. 

In its announcement Tuesday, Cambridge, MA-based Jounce noted the trial was powered to detect a 20% absolute difference in the pooled combination doses compared to pimivalimab alone. The actual difference was 7%, which meant the study failed to achieve its primary endpoint. 

According to Jounce, the trial tested two pulsatile and differentiated doses of vopratelimab in the combination groups against pimivalimab monotherapy. The primary endpoint was the mean percent change from baseline tumor size in all measurable lesions. The averages were taken at 9 and 18 weeks and assessed by a central independent radiology review. 

In the combination dose cohort assessing the lowest dose of vopratelimab (0.03mg/kg), Jounce reported that an "interesting trend" was noticed. There was an absolute mean change of 15%, and in the prespecified secondary endpoints of overall response rate, the difference was 40% compared to 25% in pimivalimab alone. Jounce also noted that in this dosing level, there was a six-month progression-free survival of 80% compared to 33% for pimivalimab alone.

Despite what was seen in this lower dose cohort, the overall trial failed to reach its primary goal. 

Richard Murray, president and chief executive officer of Jounce, praised the clinical team. Despite the pandemic and war complications, Murray said the researchers “did an outstanding job” on a complex biomarker-selected trial. 

“Although we are intrigued by the preliminary efficacy trends, particularly the landmark PFS and ORR in the lower vopra dose combination arm, the SELECT results do not support moving into registration studies as had been our previous goal. We will re-evaluate the vopra program in the context of our broader pipeline in the coming months,” Murray said.

He added that the company continues to be pleased with the activity of the anti-PD-1 drug candidate pimivalimab. Murray noted that its ongoing activity in clinical studies warrants continued investigation in other combination trials. 

In the SELECT trial, vopratelimab was well tolerated. The company also noted that the frequency and types of adverse events in the combination cohorts were comparable to the monotherapy cohort. Most adverse events were mild to moderate, and there were few treatment-related serious adverse events. 

Data from the SELECT study will be presented at the ESMO Immuno-Oncology Congress in December 2022. 

"We remain focused on our mission of delivering meaningful and long-lasting benefit to cancer patients through the discovery and pursuit of therapies that target new mechanisms of immune suppression across different types of immune cells, and bringing the right immunotherapies to the right patients," Murray added in the statement. 

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