On February 6, 2020 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported new data on the identification of the predictive biomarker to be used for patient selection in the SELECT clinical trial of vopratelimab (vopra), in addition to a research collaboration with NanoString (NASDAQ: NSTG) (Press release, Jounce Therapeutics, FEB 6, 2020, View Source [SID1234553945]). The new data introduces TISvopra, a baseline RNA signature with a threshold optimized for the emergence of ICOS hi CD4 T cells, a vopratelimab pharmacodynamic biomarker not associated with PD-1 inhibitor therapy. When applied to ICONIC clinical data, TISvopra predicted clinical outcomes from the ICONIC trial better than PD-L1 immunohistochemistry (IHC). These results are being presented today at the 2020 ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium Annual Meeting in Orlando, Florida.
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"We are excited to announce these two new developments supporting our upcoming SELECT clinical trial of vopratelimab and our own PD-1 inhibitor. The new data presented today at ASCO (Free ASCO Whitepaper)-SITC reveal the identification of TISvopra as a baseline predictive biomarker associated with the emergence of ICOS hi CD4 T cells. When applied to ICONIC clinical data, TISvopra then predicted clinical benefit in patients who received vopratelimab alone or in combination with nivolumab. This, coupled with our new research collaboration with NanoString, reflects our commitment to patient selection strategies to identify those most likely to benefit from our novel immunotherapies," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "The identification of TISvopra is a crucial step forward in the development of vopratelimab, and we plan to initiate the Phase 2 SELECT trial using this biomarker in mid-2020."
Key highlights from the poster, titled "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" include:
TISvopra is an 18 gene RNA Tumor Inflammation Signature (TIS), utilized with a vopratelimab-specific threshold and was identified as a biomarker predictive of ICOS hi CD4 T cell emergence. TISvopra positive patients treated with vopratelimab alone or in combination with nivolumab also showed improved clinical benefit (response rate, six month and nine month landmark progressive free survival and overall survival) as compared with TISvopra negative patients in the ICONIC trial.
TIS includes genes associated with integral elements of CD4 T cell activation that may contribute to a more comprehensive immune response.
The TISvopra threshold was chosen to optimize prediction of ICOS hi CD4 T cell emergence and was more predictive of clinical benefit than PD-L1 IHC in the ICONIC trial.
The emergence of ICOS hi CD4 T cells is a vopratelimab, but not a PD-1 inhibitor, pharmacodynamic biomarker linked to clinical benefit in the ICONIC trial.
In the upcoming SELECT trial, TISvopra will be used to select patients for treatment with vopratelimab and JTX-4014, Jounce’s PD-1 inhibitor.
The poster is available in the "Our Pipeline" section of the Jounce Therapeutics website under "Publications" at www.jouncetx.com.
Jounce also announced a research collaboration with NanoString to support the application of the predictive biomarker to be used in the SELECT trial. Under the terms of the collaboration, Jounce and NanoString will apply an optimized selection threshold of the TIS based on the emergence of ICOS hi CD4 T cells (TISvopra). The TISvopra clinical trial assay will be implemented on the nCounter Dx Analysis System.
About the Phase 2 SELECT Clinical Trial
The Phase 2 SELECT clinical trial is a randomized, ex-U.S. trial to evaluate the efficacy of JTX-4014 alone and in combination with vopratelimab. The trial is powered to show statistical superiority of vopratelimab plus JTX-4014 compared to JTX-4014 alone in a biomarker-selected patient population. Jounce expects to enroll approximately 75 immunotherapy naïve second-line non-small cell lung cancer (NSCLC) patients. Patients will be prescreened for the TISvopra biomarker. Jounce estimates that approximately 20% of the prescreened NSCLC patients will be above the TISvopra threshold and potentially eligible for the trial. Jounce expects to initiate the SELECT trial in mid-2020 and report preliminary efficacy and biomarker relationships to clinical outcomes from up to 75 patients in 2021.
About Vopratelimab
Jounce’s lead product candidate, vopratelimab, is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. Vopratelimab is currently being assessed in the Phase 2 EMERGE clinical trial in a sequenced combination with ipilimumab in patients with NSCLC who were previously treated with PD-1/PD-L1 inhibitor therapies. Jounce is also planning to initiate the Phase 2 SELECT clinical trial of vopratelimab with its investigational PD-1 inhibitor, JTX-4014, in TISvopra biomarker-selected patients. Vopratelimab was previously assessed in the Phase 1/2 ICONIC trial and was found to be safe and well-tolerated, alone and in combination with each of the anti-PD-1 antibodies nivolumab and pembrolizumab, as well as with ipilimumab, an antibody that binds to CTLA-4.