Jounce Therapeutics Announces Update on Vopratelimab Program
CAMBRIDGE, Mass.,?Nov. 02, 2020?(GLOBE NEWSWIRE) --?Jounce Therapeutics, Inc.?(NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, today provided an update on its vopratelimab (vopra) program. The intent of the EMERGE Phase 2 trial was to induce ICOS hi CD4 T cells with ipilimumab, and then administer vopra with the goal of increasing proliferation and expansion of these ICOS hi CD4 T cells, which were associated with durable clinical benefit in the ICONIC trial of vopra alone and in combination with a PD-1 inhibitor. Early evaluation of the data from the EMERGE trial of vopra in combination with ipilimumab in PD-(L)1 inhibitor experienced non-small cell lung cancer (NSCLC) patients indicates the trial will not meet pre-specified interim criteria for continuation of enrollment. Therefore, the EMERGE trial will not be expanded. The company also announced the first patient dosed in the SELECT Phase 2 trial, supporting vopra?s potential in combination with JTX-4014 in immunotherapy na?ve biomarker-selected NSCLC patients.
"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. ?Less than 50% of the EMERGE patients had emergence of ICOS hi CD4 T cells after ipilimumab treatment, indicating that CD4 T cell activation by CTLA-4 inhibitors may be impaired in PD-(L)1 inhibitor resistant patients. Patients who have progressed on or after PD-1 inhibitor therapies represent a large and growing unmet need and new therapeutic mechanisms may be needed to more effectively treat these patients. We would like to thank the patients, investigators and study teams for their participation in the EMERGE trial.?
?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,? said?Richard Murray, Ph.D., chief executive officer and president of?Jounce Therapeutics. ?Our pipeline beyond vopra is focused on these novel approaches and we believe our existing programs, particularly, JTX-8064, our lead macrophage program targeting LILRB2 (ILT4), and other programs from our discovery platform, are poised to make meaningful contributions to both the PD-(L)1 na?ve and resistant populations.?
EMERGE?Enrollment,?Dosing?and Safety
Fifty-nine patients were enrolled, 50 of whom are evaluable based on pre-specified criteria which required at least one dose of each drug and at least one CT scan for response assessment or clinical progression without a CT. Vopra continued to be safe and the combination with ipilimumab was well tolerated. The type and frequency of adverse events were similar to those seen with ipilimumab.
Summary of EMERGE?Preliminary?Efficacy?Data
*?Dose not protocol-specified, due to dosing error at a single study site;?**?Confidence interval;?***?Not estimable; Ipilimumab was dosed for a maximum of 4 doses. Data as of?October 26, 2020
The data for all doses combined, with or without including the 10 subjects dosed at .01 mg/kg, did not meet the pre-specified criteria for continuation of enrollment in the trial, with tumor reduction in 38% of patients and one confirmed RECIST 1.1 response. In the .10 mg/kg cohort, 55% of patients had tumor reduction and confirmed overall response rate (ORR) is 4.5%. Median overall survival (OS) for all dose groups combined was 11.6 months and has not been reached in the .10 and .03 mg/kg cohorts. Nine patients remain on study, including four patients continuing to benefit on vopra alone after completion of up to four ipilimumab doses. The biomarker analysis is not yet complete.
EMERGE?Interim Analysis?Clinical?Criteria?to Expand?Trial
0.10 mg/kg vopratelimab + 3 mg/kg ipilimumab | 0.03 mg/kg vopratelimab + 3 mg/kg ipilimumab | 0.01 mg/kg*?vopratelimab + 3 mg/kg ipilimumab | All doses combined | |
Evaluable patients: n | 22 | 18 | 10 | 50 |
Patients with tumor reduction: n (%) | 12 (54.5) | 3 (16.7) | 4 (40.0) | 19 (38.0) |
Confirmed ORR: n (%) | 1 (4.5) | 0 (0.0) | 0 (0.0) | 1 (2.0) |
OS: Median (95% CI**) | NE***?(5.3, NE) | NE (4.5, NE) | 8.8 (1.7, NE) | 11.6 (6.0, NE) |
Patients remaining on study | 8 | 1 | 0 | 9 |
- Tumor reduction in = 50% of patients,
- Median overall survival tracking to = 13 months, and
- Overall response rate = 10%