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Jounce Discontinues Phase 2 NSCLC Trial After its Combo Therapy with Ipilimubab Folds
On November 2nd, shares of Jounce Therapeutics crashed after the company announced its discontinuation of patient enrollment in the Emerge phase 2 trial evaluating vopratelimab (vopra) in combination with Bristol Myers Squibb’s Yervoy in treating NSCLC. Despite this drop, the company stock rose back up to 7 dollars per share less than a day later from its low of $6.01. While this is still a net loss from its per-share price of $8.32 from the day before the price drop, it does indicate the market´s quick forgiveness of Jounce.
“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 Therapeutics.
EMERGE Trial Details
The EMERGE 2 trial intended to induce ICOS hi CD4 T cells with ipilimumab and then administer vopra with the goal of increased proliferation and expansion, which were associated with durable clinical benefit in the ICONIC trial of just vopra and vopra with a PD-1 inhibitor.
Of the 59 patients that enrolled, 50 could be evaluated based on criteria that required at least one dose of each drug and at least one CT scan for assessment or clinical progression without a CT. Vopra continued to be safe alone and with ipilimumab with a similar occurrence of adverse events as with ipilimumab alone.
Interim analysis criteria were selected to provide evidence that a combination of vopra and ipilimumab could potentially be superior to docetaxel in a randomized Phase 3 trial with an overall survival endpoint. These criteria consisted of tumor reduction in half of the patients or more, a median overall survival rate of at least 13 months, and an overall response rate of at least 10%.
Comparison of EMERGE and SELECT Trials
Vopratelimab is a monoclonal antibody that binds to and activates ICOS, an inducible T cell CO-Stimulator protein located on the surface of certain T cells commonly found in many solid tumors. Vopratelimab is being assessed in the SELECT Phase 2 clinical trial in combination with Jounce’s internal investigational PD-1 inhibitor, JTX-4014, compared to JTX-4014 alone in immunotherapy naïve NSCLC patients.
SELECT and EMERGE were developed to address distinct hypotheses for vopra and ICOS hi CD4 cells to improve patient outcomes. These trials cater to different populations, PD-(L)1 inhibitor-resistant versus PD-(L)1 inhibitor naïve, and biomarker selected.
The SELECT trial began enrolling approximately 75 immunotherapy naïve NSCLC (non-small cell lung cancer) patients in October who were pre-selected with the TISvopra predictive biomarker. The TISvopra predictive biomarker is an 18 gene RNA tumor inflammation signature that predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor. SELECT is powered to demonstrate the statistical superiority of the combination of vopratelimab plus JTX-4014 compared to JTX-4014 alone. Data for the SELECT trial is anticipated for 2021. This supports vopra’s potential for biomarker-selected NSCLC patients in combination with JTX-4014, who are immunotherapy naïve.
Jounce has licensed rights to JTX-1811, a monoclonal antibody targeting CCR8 and designed to selectively deplete T regulatory cells in the tumor microenvironment, to Gilead Sciences, Inc. This agreement was made back in September of 2020 and began with Gilead’s agreement to pay Jounce $85 million upfront along with a $35 million equity investment. In total, Jounce could earn $685 million from milestone payments made for the progress of JTX-1811. If the drug reaches the market, Gilead must pay Jounce royalties from sales. Under the terms of the deal, Gilead will have exclusive rights to develop the drug after Jounce gets JTX-1811 to the point of being approved for a clinical trial.
Thankfully for Jounce, this is not their first Rodeo. In 2016, it landed a $225 million upfront deal from Celgene in an alliance spanning several cancer immunotherapy candidates and eventually became the deal with Bristol Myers Squibb that just recently dissolved. By using partnerships with larger companies, Jounce can provide their drugs with a platform and support. Having experience in this approach and its money-saving potential and market confidence will make rebounding from the cancellation of one clinical trial very possible for Jounce.
By Eduardo Longoria
Editor: Rajaneesh K. Gopinath, Ph.D.
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