On June 2, 2018 Jounce Therapeutics, Inc. (NASDAQ:JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that its preliminary data from its ongoing Phase 1/2 ICONIC trial, an adaptive design, open-label trial evaluating JTX-2011 alone and in combination with nivolumab in patients with advanced solid tumors (Press release, Jounce Therapeutics, JUN 2, 2018, View Source;p=RssLanding&cat=news&id=2352867 [SID1234527089]). Safety and preliminary clinical activity data from all evaluable patients across multiple tumor types will be presented in an oral presentation today, Saturday, June 2, 2018 at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.
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"We are encouraged by the early signal of clinical activity in heavily pre-treated patients, accompanied by an ICOS pharmacodynamic biomarker. We believe that this biomarker may help guide further development of JTX-2011," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "Importantly, JTX-2011 continues to be safe and well-tolerated both as a single agent and in combination with nivolumab. We look forward to continuing clinical evaluation of JTX-2011, including initiation of new combination dose escalation cohorts within the ICONIC trial of JTX-2011."
The ICONIC study (ICOS AgONist Antibody for Immunotherapy in Cancer Patients) is an open label, dose escalation and expansion clinical study of JTX-2011 alone and in combination with a fixed dose of nivolumab in patients with advanced solid tumors. Patients were heavily pre-treated with approximately 65 percent having received 3 or more prior therapies (i.e. 4th line or greater); approximately 65 percent discontinued during the first three cycles. The adaptive design includes Parts A and B (Phase 1), and C and D (Phase 2), with the Phase 2 cohorts enriched for high ICOS expression. The data presented today include preliminary efficacy data from all evaluable patients as of an April 4, 2018 cut-off date. The Phase 1 portion of ICONIC was a dose escalation study to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). The patients in Phase 2 received JTX-2011 0.3 mg/kg every 3 weeks alone or in combination with nivolumab 240 mg every 3 weeks. Preliminary efficacy evaluation included tumor reductions and RECIST (response evaluation criteria in solid tumors) responses.
Summary of JTX-2011 ICONIC Data
Safety
JTX-2011 was well tolerated alone and in combination with nivolumab 240 mg every 3 weeks. The overall safety profile observed was consistent with previously reported data from the Phase 1 portion of the ICONIC trial.
Clinical Activity
Gastric Cancer
A RECIST partial response (PR) with JTX-2011 monotherapy was observed in 1 of 8 Phase 2 patients (7 PD-1 inhibitor naïve, including PR), ongoing at 8.5+ months.
Two RECIST PRs with JTX-2011 plus nivolumab were observed in 1 of 4 Phase 1 patients (all PD-1 inhibitor naïve) and 1 of 28 Phase 2 patients (22 PD-1 inhibitor naïve, including PR), ongoing at 11+ and 4+ months, respectively.
Disease control(1) was observed in 10 of 28 and tumor reductions were observed in 8 of 28 Phase 2 patients treated with JTX-2011 plus nivolumab, including both PD-1 inhibitor naïve and PD-1 inhibitor failures.
Triple Negative Breast Cancer (TNBC)
A RECIST PR with JTX-2011 plus nivolumab was observed in 1 of 17 Phase 2 patients (16 PD-1 inhibitor naïve, including PR), ongoing at 4+ months.
Disease control was observed in 3 of 17 and tumor reductions were observed in 2 of 17 Phase 2 patients treated with JTX-2011 plus nivolumab, all PD-1 inhibitor naïve.
Head and neck squamous cell cancer (HNSCC) PD-1 inhibitor failures
Disease control was observed in 2 of 16 and tumor reductions were observed in 1 of 16 Phase 2 patients treated with JTX-2011 plus nivolumab, all PD-1 inhibitor failures, of whom over 50 percent were refractory(2) to prior PD-1 inhibitors.
Non-small cell lung cancer (NSCLC) PD-1 inhibitor failures
Disease control was observed in 7 of 12 and tumor reductions were observed in 4 of 12 Phase 2 patients treated with JTX-2011 plus nivolumab, all PD-1 inhibitor failures.
(1) Disease control= confirmed PR + SD ≥ 9 weeks
(2) Refractory= best response to prior PD-1 inhibitor was progressive disease
Biomarkers
In a preliminary analysis of evaluable fresh pre-treatment biopsies, rates of disease control and tumor reduction appear higher in subjects with high ICOS scores.
An ICOS pharmacodynamic biomarker (emergence of peripheral blood ICOS high CD4 T cell population) appears to associate with anti-tumor activity.
Present in 7 of 7 subjects with target lesion PRs
Absent in 10 of 10 subjects with progressive disease
Based on preliminary signals of clinical activity associated with an ICOS pharmacodynamic biomarker, Jounce is advancing clinical evaluation of JTX-2011. The next steps for the program include continuing to evaluate the ongoing data and the initiation of two new dose escalation cohorts within the ICONIC trial of JTX-2011, one in combination with ipilimumab and one in combination with pembrolizumab. The new ipilimumab combination cohort may enable Jounce to explore a new combination mechanism that is supported by clinical and pre-clinical research. Exploration with pembrolizumab at its approved q3w dose and schedule may allow the Company to evaluate JTX-2011in combination with a PD-1 inhibitor in earlier lines of therapy.
"We look forward to evaluating the new additional combinations with JTX-2011. From our founding science, the platform we have built, and the team we have in place, we believe we are well positioned to optimize the development of JTX-2011," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "We are grateful to all of the patients who have participated in our trial, their families, our investigators and their study teams. This was a complex biomarker heavy trial that was well executed by the Jounce team."
ICONIC Enrollment Status
Phase 1 has completed enrollment and Phase 2 is nearing completion of enrollment. Given the pace of enrollment of the combination cohorts in gastric cancer, TNBC, HNSCC, NSCLC and the overall quantity of the data collected, Jounce made the decision to stop recruitment of other solid tumors and of the more slowly enrolling monotherapy and melanoma combination cohorts.
Jounce Therapeutics to Host Event and Webcast
Jounce Therapeutics will host an investor and analyst event beginning at 6:30 p.m. CT (7:30 p.m. ET) with a live webcasted presentation beginning at 7:00 p.m. CT (8:00 p.m. ET), on Monday, June 4, 2018. To access the live webcast, please visit the "Events & Presentations" page in the Investors and Media section of the company’s website at www.jouncetx.com. The webcast will be archived and made available for replay on the company’s website approximately two hours after the call and will be available for 30 days thereafter.
About JTX-2011
Jounce’s lead product candidate, JTX-2011, is a monoclonal antibody that binds to and activates ICOS, the Inducible T cell COStimulator, a protein on the surface of certain T cells. Preclinical data support that JTX-2011 may have a dual mechanism of action that stimulates anti-tumor T effector cells, and also reduces the immunosuppressive T regulatory cells in the tumor microenvironment. The company is developing JTX-2011 to treat solid tumors as a single agent and in combination with other therapies.