Vopratelimab Plus Pimivalimab Fails to Meet Tumor Reduction End Point in Select Metastatic NSCLC

The addition of vopratelimab (JTX-2011) to pimivalimab (formerly JTX-4014) did not elicit a significant mean percent change of baseline tumor size in all measurable lesions vs pimivalimab alone in patients with immunotherapy-naïve, metastatic non–small cell lung cancer (NSCLC) who were positive for the TIS^vopra predictive biomarker, according to findings from the phase 2 SELECT trial (NCT04549025).¹

The study was powered to detect a 20% absolute difference in baseline tumor size at 9 and 18 weeks of the pooled combination doses of vopratelimab/pimivalimab. The actual difference was 7%, failing to meet the trial’s primary end point. Across all patients who received vopratelimab/pimivalimab (n = 33), the mean change in tumor size from baseline was 0.23% (95% CI, -20.10% to 20.56%), compared with 7.33% (95% CI, -12.46% to 27.12%) in patients given pimivalimab alone (n = 36).

In patients given pimivalimab plus 0.1 mg/kg of vopratelimab (n = 18), the mean change in tumor size from baseline was 8.35% (95% CI, -19.94% to 36.65%). Patients given pimivalimab plus 0.03 mg/kg of vopratelimab (n = 15) experienced a mean change in tumor size from baseline of -7.89% (95% CI, -37.15% to 21.37%).

“The team did an outstanding job executing on a complex biomarker-selected trial impacted by both the pandemic and the war in Ukraine. Although we are intrigued by the preliminary efficacy trends, particularly the landmark progression-free survival [PFS] and overall response rate [ORR] in the lower vopratelimab dose combination arm, the SELECT results do not support moving into registration studies as had been our previous goal. We will reevaluate the vopratelimab program in the context of our broader pipeline in the coming months,” Richard Murray, PhD, chief executive officer and president of Jounce Therapeutics, stated in a press release.

“We continue to be pleased with pimivalimab’s activity, which supports its continued use in our ongoing and future combination trials. We plan to submit a clinical abstract to present the entire SELECT study, including more mature data, at the ESMO Immuno-Oncology Congress in December 2022.”

Vopratelimab is a clinical-stage monoclonal antibody that binds to and activates the inducible T-cell co-stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. Pimivalimab is a fully human IgG4 monoclonal antibody designed to block binding to PD-L1/2.

The SELECT trial evaluated vopratelimab at 2 dose levels in combination with pimivalimab vs pimivalimab alone in patients with NSCLC who were positive for the TIS^vopra predictive biomarker and experienced progression of locally advanced or metastatic disease after 1 prior platinum-based chemotherapy regimen.² To enroll, patients were required to have histologically or cytologically confirmed diagnosis of NSCLC with evaluable or measurable disease per RECIST v1.1 with at least 1 measurable lesion. Patients also needed to have a confirmed tumor RNA signature score, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate organ function.

Key exclusion criteria included concurrent anticancer treatment, the expected need for any other form of antineoplastic therapy while on the study, current or past participation in a study evaluating an investigational agent in the metastatic setting, chemotherapy within 28 days of first study treatment, prior immunotherapy, prior whole brain radiation, or the presence of select EGFR mutations.

Patients were randomized to receive 0.1 mg/kg of vopratelimab plus pimivalimab, 0.03 mg/kg of vopratelimab plus pimivalimab, or pimivalimab alone.

Along with the primary end point of change in measurable tumor size at 9 and 18 weeks, secondary end points included ORR, PFS, landmark PFS, disease control rate (DCR), duration of response, and overall survival.

Additional data showed that the pooled ORR for patients given the combination was 27.3%, with a complete response (CR) rate of 3% and a partial response (PR) rate of 24.2%. Furthermore, 45.5% of patients had stable disease and 18.2% experienced progressive disease for a DCR of 72.7%. Three patients were not reported, not evaluable, or terminated treatment early.

In the pimivalimab monotherapy arm, the ORR was 25%, with CR and PR rates of 2.8% and 22.2%, respectively. Additionally, 36.1% had stable disease and 27.8% had progressive disease for a DCR of 61.1%. Four patients were not reported, not evaluable, or terminated treatment early.

The 6-month landmark PFS rate was 54% (95% CI, 35%-69%) in patients who received the vopratelimab/pimivalimab combination at any dose. The landmark PFS rate was 33% (95% CI, 16%-50%) for patients given pimivalimab alone.

The findings showed the 0.03 mg/kg dose of vopratelimab provided a shorter duration of receptor occupancy compared with the 0.1 mg/kg dose. Investigators observed no association between baseline PD-L1 status and ORR.

Regarding safety, the frequency and types of adverse effects (AEs) reported in the combination cohorts were comparable to those in the monotherapy cohort. Most AEs were mild or moderate, and few treatment-related AEs were observed.

References

1. Jounce Therapeutics reports results from phase 2 randomized SELECT trial testing 2 different doses of vopratelimab in TIS^vopra biomarker-selected patients. News release. Jounce Therapeutics. August 30, 2022. Accessed August 31, 2022. https://bit.ly/3wI3Bc2
2. Study of PD-1 inhibitor JTX-4014 alone and in combination with vopratelimab in biomarker-selected subjects with metastatic NSCLC after one prior platinum-containing regimen (SELECT). ClinicalTrials.gov. Updated June 23, 2022. Accessed August 31, 2022. https://clinicaltrials.gov/ct2/show/NCT04549025