On March 16, 2023 Jounce Therapeutics, Inc. (Nasdaq: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that patients from the INNATE Phase 2 trial in the ovarian cancer combination cohort with platinum resistant ovarian cancer are experiencing deep and durable responses based on a pre-planned informal data review (Press release, Jounce Therapeutics, MAR 16, 2023, View Source [SID1234628925]).

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The INNATE trial evaluates JTX-8064 as a monotherapy and in combination with the PD-1 inhibitor pimivalimab in patients with advanced solid tumors. JTX-8064, is a humanized IgG4 monoclonal antibody designed to specifically bind to the macrophage receptor Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4), inhibiting LILRB2 binding with its ligands which may result in reprogramming immune-suppressive macrophages to enhance anti-tumor immunity.

A data review was conducted on March 15, 2023 to assess the potential to achieve proof-of-concept (POC) in the ovarian cancer combination cohort of the INNATE trial. In this cohort, 35 patients with third- and fourth-line platinum resistant ovarian cancer were treated with JTX-8064 and Jounce’s PD-1 inhibitor, pimivalimab. There were five RECIST 1.1 responders, four of which are confirmed, with all five patients remaining on study for over six months with continued tumor reduction over time. The remaining 30 patients have discontinued treatment. Upon confirmation of a fifth confirmed partial response (PR), the ovarian combination cohort would meet Jounce internal criteria for POC, based on a statistically meaningful improvement over the benchmark of pembrolizumab alone in the analogous setting. In patients with one to six prior lines of therapy for ovarian cancer, pembrolizumab monotherapy demonstrated a response rate of 8.5%, with duration of response of 10.2 months. Two of the five responders in INNATE have a PD-L1 score of zero, indicating a low likelihood of response to a PD-1 inhibitor. The combination was well tolerated with <10% of patients reporting Grade 3 or greater related adverse events.

Ovarian Cancer Combination Cohort Responders

Subject PD-L1
(CPS) Response
Assessment When was uPR
demonstrated Current status
1 55% cPR Wk 9 -82.8% (wk 45)
2 15% cPR Wk 18 -66.4% (wk 36)
3 5% cPR Wk 18 -87.6% (wk 27)
4 0% cPR Wk 18 -78.26% (wk 27)
5 0% uPR Wk 27 -40% (wk 27)

Ovarian Combination Cohort Target Lesion % Change from Baseline over Time

"Following this analysis, we are pleased to see these results demonstrating deep and durable responses in patients, including those with a PD-L1 score of 0%, on a very well tolerated regimen. These results lead us to believe that there is a potential for meaningful clinical benefit with this combination in patients with few durable therapeutic options," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "Tumor reduction was observed at 9 weeks in all the responding patients in the ovarian cancer cohort of the INNATE trial, but most did not achieve a PR until week 18, which delayed our ability to assess efficacy in this cohort. Platinum resistant ovarian cancer is a patient population with significant unmet need and progressive disease is often associated with debilitating symptoms."

Enrollment has been completed in all cohorts in the INNATE trial. In addition to the patients with ovarian cancer, both durable responses and stable disease have occurred in patients with renal cell carcinoma, biliary tract cancer, and first-line and second/third-line head and neck squamous cell carcinoma, but the ovarian data is the most encouraging with potential to achieve pre-determined POC criteria.

As previously announced, Jounce is seeking to partner JTX-8064. Jounce continues to believe a company with additional resources and a longer value creation timeline could potentially advance this program for the benefit of cancer patients.