JTX-8064/Pimivalimab Yields Robust Responses in Pretreated Ovarian Cancer

Patients with platinum-resistant ovarian cancer experienced deep and durable responses after receiving treatment with JTX-8064 plus pimivalimab, according to a press release on findings from a pre-planned data review of the phase 2 INNATE trial (NCT04669899).

"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," according to the manufacturers of JTX-8064 and pimivalimab.

As of a data review conducted on March 15, 2023, 5 of 35 patients responded to treatment with JTX-8064 plus pimivalimab per RECIST v1.1 criteria and remained on study treatment for over 6 months with continued tumor reduction over time. With confirmation of a fifth partial response, the regimen met internal criteria for proof-of-concept in the ovarian cancer combination cohort based on statistically significant improvements vs the benchmark set by pembrolizumab (Keytruda) monotherapy in the analogous setting.

In patients who received 1 to 6 prior lines of therapy for ovarian cancer, pembrolizumab yielded an overall response rate (ORR) of 8.5% and a median duration of response (DOR) of 10.2 months.

A total of 30 patients discontinued treatment with JTX-8064 plus pimivalimab in the ovarian cancer cohort. Additionally, 2 of 5 responders had a PD-L1 score of 0, which indicated a low probability of responding to PD-1 inhibitors. Investigators reported that the combination was well tolerated, as less than 10% of patients had grade 3 or higher adverse effects (AEs.)

“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,” Richard Murray, PhD, chief executive officer and president of Jounce Therapeutics, said in the press release. “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.”

JTX-8064 is a humanized IgG4 monoclonal antibody that specifically binds to macrophage receptor LILRB2/ILT4, thereby inhibiting LILRB2 binding with its ligands. Investigators believe this inhibition may reprogram immune-suppressive macrophages to enhance anti-tumor immunity.

Investigators of the open-label phase 2 INNATE trial are evaluating JTX-8064 alone or in combination with pimivalimab as a treatment for patients with advanced solid tumor malignancies. In the study’s ovarian cancer combination cohort, 35 patients with third- and fourth-line platinum-resistant ovarian cancer received JTX-8064 plus pimivalimab.

The primary end points of the trial include incidence of dose-limiting toxicities, treatment-emergent AEs (TEAEs), serious TEAEs, and treatment discontinuation due to AEs. Secondary end points include ORR and disease control rate per RECIST v1.1 guidelines, DOR, progression-free survival, and overall survival.

Patients 18 years or older with histologically confirmed third- or fourth-line platinum-resistant ovarian cancer are eligible for enrollment in the combination cohort of the INNATE trial. Additional inclusion criteria include having measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and a predicted life expectancy of at least 3 months.

Patients receiving concurrent anticancer therapy or those who received prior infusions of JTX-8064 are not eligible for enrollment on the trial. Patients are also unsuitable for enrollment if they have symptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation.

Reference

Jounce Therapeutics announces results from pre-planned data review of INNATE phase 2 trial of JTX-8064 and pimivalimab demonstrating deep and durable responses in platinum resistant ovarian cancer. News release. Jounce Therapeutics. March 16, 2023. Accessed March 20, 2023. bit.ly/40fwEQG