Jounce sinks as it ditches phase 2 Yervoy combo trial

Jounce Therapeutics and its lead prospect took a hit Monday as its stopped enrollment in a phase 2 lung cancer trial. The company was testing the drug alongside Bristol Myers Squibb’s Yervoy in patients with non-small cell lung cancer, but an early look at the data showed the combo was unlikely to succeed.

The study, called EMERGE, was testing three dose levels of Jounce’s drug, vopratelimab, with Opdivo in 59 patients who had already tried PD-1 or PD-L1 inhibitors like Bristol Myers Squibb’s Opdivo or Merck’s Keytruda. Yervoy works by targeting CTLA-4, a receptor found on T cells that acts as a “brake” on the immune system. Adding vopratelimab to the mix, Jounce thought, would activate ICOS, a different protein on the T cells, to boost their proliferation and expansion after Yervoy released the immune brake. But data from 50 evaluable patients said otherwise.

Jounce’s stock plunged more than 18% on the news Monday and has not bounced back.

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Only one patient saw their tumors shrink enough to be considered a responder, while 19 (38%) patients saw some shrinkage that did not meet this threshold. Of the 50 patients, only nine are still participating in the study.

“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,” said Beth Trehu, M.D., chief medical officer at Jounce, in a statement.

Less than half of the patients saw a boost in T cells after taking Yervoy, suggesting that targeting CTLA-4 may not work as well in patients whose cancer does not respond to PD-1 or PD-L1 inhibitors, Trehu added.

“The PD-(L)1 experienced or resistant population continues to prove difficult to treat. To bring necessary benefit to these patients it is becoming clearer that novel approaches beyond T cells may be needed as part of the solution,” Jounce CEO Richard Murray, Ph.D., said in the statement.

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This trial may be over, but it’s not the end for vopratelimab. The company announced the start of a different phase 2 study, SELECT, which combines the drug with Jounce’s PD-1 drug, JTX-4014, in patients with non-small cell lung cancer who have not tried immunotherapy. And it has a pair of preclinical programs targeting LILRB2 and CCR8, which could become part of the “novel approaches” Murray mentioned.

The company is developing the CCR8 program, JTX-1811, with Gilead Sciences. Jounce lost another partnership earlier this year when a 2016 pact inked with Celgene fell victim to the latter’s acquisition by Bristol Myers Squibb.