SELECT Study of Vopratelimab With/Without Pimivalimab Misses Primary End Point in NSCLC

Top-line data from the SELECT trial of vopratelimab plus pimivalimab vs pimivalimab alone missed its primary end point of mean tumor change but showed encouraging trends for secondary end points.

The phase 2 SELECT trial of vopratelimab (JTX-2011) plus pimivalimab (JTX-4014) vs pimivalimab alone did not meet its primary end point of mean tumor change in patients with metastatic non–small cell lung cancer (NSCLC) who are PD-1/PD-L1 inhibitor naïve and have progressed on a platinum-based chemotherapy regimen.1

However, top-line data from the trial did show encouraging trends in improved mean tumor change over 9 and 18 weeks, overall response rate (ORR), and progression-free survival (PFS) in the low dose vopratelimab in combination with pimivalimab arm compared with pimivalimab alone.

Vopratelimab, is a monoclonal antibody that binds to and activates inducible costimulator (ICOS), a protein on the surface of certain T cells that may stimulate an immune response against tumor cells.

“Although we are intrigued by the preliminary efficacy trends, particularly the landmark PFS and 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 re-evaluate the vopra program in the context of our broader pipeline in the coming months,” said Richard Murray, PhD, chief executive officer and president of Jounce Therapeutics, in a press release.

The phase 2 SELECT trial (NCT04549025) evaluated 2 pulsatile and differentiated doses of vopratelimab in the combination groups vs pimivalimab monotherapy to evaluate the efficacy, safety, and tolerability of both the combination and monotherapy in patients with metastatic NSCLC who have progressed on a platinum-based chemotherapy regimen and are PD-1/PD-L1 inhibitor naïve.2

Enrollment in the trial was open to patients aged 18 years and older with histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) with evaluable or measurable disease with at least 1 measurable lesion. Patients must have had a confirmed tumor RNA signature score, progression of locally advanced or metastatic NSCLC after 1 prior systemic antineoplastic platinum-containing regimen, an ECOG performance status of 0 or 1, a predicted life expectancy of ≥ 3 months, and adequate organ function.

The primary end point of the trial was mean percent change from baseline in tumor size in all measurable lesions as averaged over 9 and 18 weeks and assessed by central independent radiology review. Secondary end points included ORR, PFS, landmark PFS, disease control rate (DCR), median duration of response, and median overall survival.

Findings of the preliminary data readout showed that 16.7% of patients responded on the higher dose of vopratelimab with pimivalimab (0.1 mg/kg) compared with 40% percent of those receiving a lower dose (0.03mg/kg) of the monoclonal antibody with pimivalimab. In the pimivalimab monotherapy arm, 25% of patients responded. Also, in the combination dose cohort who received the lowest dose of vopratelimab, trends were observed in the primary end point with an absolute mean change of 15%.

Patients who received the low-dose regimen of vopratelimab plus pimivalimab also saw a higher proportion of patients who did not progress within 6 months of treatment at 80% vs 29% in the higher-dose arm and 33% in the pimivalimab monotherapy arm, respectively.

While the study aimed to detect a 20% absolute difference of the pooled combination doses vs pimivalimab monotherapy, the actual difference was 7%.

Though the study did not meet its primary end point, vopratelimab appeared to be well tolerated and the frequency and types of adverse events (AEs) for patients who were given the combination were comparable to those given the monotherapy. Most AEs were mild to moderate, and there were few treatment-related serious AEs.

Pimivalimab monotherapy continues to demonstrate safety and clinical activity in this patient population and the company hopes to present data from this study at an upcoming medical conference.1

“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. We remain focused on our mission of delivering meaningful and long-lasting benefit to cancer patients through the discovery and pursuit of therapies that target new mechanisms of immune suppression across different types of immune cells, and bringing the right immunotherapies to the right patients,” added Murray, in the press release.

References:
Jounce therapeutics reports results from phase 2 randomized SELECT trial testing 2 different doses of vopratelimab in TISvopra biomarker-selected patients. News release. Jounce Therapeutics. August 30, 2022. Accessed August 31, 2022. https://yhoo.it/3KxSGYe
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#wrapper