JTX-8064 Plus Pimivalimab Elicits Durable Responses in Platinum-Resistant Ovarian Cancer

The combination of JTX-8064 and pimivalimab (formerly JTX-4014) generated deep and durable responses in patients with third- or fourth-line platinum-resistant ovarian cancer, according to data from a preplanned review of the phase 2 INNATE trial (NCT04669899).¹

Findings showed that among 35 patients treated in the ovarian cancer combination cohort, 4 experienced a confirmed partial response (PR), and 1 had an unconfirmed PR. All 5 patients have remained on study treatment for more than 6 months with continued tumor reduction over time. (TABLE)

Additionally, among those 5 patients, 1 had an unconfirmed PR at week 9, 3 had unconfirmed PRs at week 18, and 1 had an unconfirmed PR at week 27. The PR remained unconfirmed in the patient who experienced the response at week 27.

The remaining 30 patients in the trial discontinued treatment.

Notably, 2 of 5 responders had a PD-L1 combined positive score (CPS) of 0, which historically indicates a low likelihood of response to a PD-1 inhibitor.

“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,” Richard Murray, PhD, chief executive officer and president of Jounce Therapeutics, stated in a news release.

“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.”

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 could lead to the reprogramming of immune-suppressive macrophages to enhance anti-tumor immunity.

INNATE is a first-in-human, phase 1/2 trial evaluating JTX-8064 as monotherapy and in combination with pimivalimab in adult patients with advanced refractory solid tumors.² Enrollment has been completed in all cohorts.¹

Patients were required to have a histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancy.² In stage 4 expansion, 1 cohort included patients with third- or fourth-line ovarian cancer who were naïve to a PD-1/L1 inhibitor.

Patients in the ovarian cancer cohort in stage 4 were treated with the combination of JTX-8064 and pimivalimab.

In stages 3 and 4, the primary efficacy end points were disease control rate, duration of response, percentage of patients with tumor reduction over time, progression-free survival, and overall survival.

Investigators have observed durable responses and stable disease in patients with renal cell carcinoma, biliary tract cancer, and first-line and second- or third-line head and neck squamous cell carcinoma during the trial.¹ However, the data for patients with ovarian cancer are the most encouraging with potential to achieve pre-determined proof-of-concept criteria.

If the fifth PR in the ovarian cancer cohort is confirmed, data will meet the Jounce internal criteria for proof-of-concept, based on a statistically meaningful improvement over the benchmark of pembrolizumab alone in the analogous setting.

Regarding safety, JTX-8064 plus pimivalimab was well tolerated. Grade 3 or higher treatment-related adverse effects were reported in less than 10% of patients.

References

1. 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. March 16, 2023. Accessed March 17, 2023. https://ir.jouncetx.com/news-releases/
2. Study of JTX 8064, as monotherapy and in combination with a PD-1 inhibitor, in adult subjects with advanced refractory solid tumor. ClinicalTrials.gov. Updated October 13, 2022. Accessed March 17, 2023. https://clinicaltrials.gov/ct2/show/NCT04669899