181P - SELECT: A phase 2 randomized trial evaluating 2 doses of vopratelimab (V) + pimivalimab (P) vs P in TISvopra selected patients (pts)

Background

SELECT is a phase 2 randomized study of P, an investigational PD-1 inhibitor (PD-1i) plus V, an investigational ICOS agonist, vs P in TIS^vopra selected, immunotherapy naïve, 2^nd line non-small cell lung cancer (NSCLC). Tumor inflammation signature (TIS) at and above a designated cut-off, termed TIS^vopra, was previously associated with improved clinical outcomes in patients treated with V +/- nivolumab. SELECT was designed to demonstrate superiority of P + V vs P in TIS^vopra selected pts and evaluate 2 doses of V with different pulsatile target engagement (TE) profiles to reduce T cell exhaustion.

Methods

69 TIS^vopra positive pts with metastatic NSCLC after 1 prior platinum-containing regimen were randomized 2:1:1 to P 1000 mg (MC1, n=36), P+V 0.1 mg/kg (CC1, n=18) or P+V 0.03 mg/kg (CC2, n=15) q6w. Primary (1°) endpoint was mean % change from baseline size of all measurable lesions averaged over 9 & 18 weeks by independent central radiology review (ICR); the study was powered to compare MC1 vs pooled CC1+CC2. Overall response rate (ORR) per RECIST v1.1 by ICR, progression free survival (PFS), and overall survival (OS) were secondary (2°) endpoints. Safety, TE and association between PD-L1 and efficacy were evaluated.

Results

1° endpoint was numerically better in CC1+CC2 vs MC1 but not statistically significant. CC2 trended favorably for 1° endpoint, ORR, and PFS. ORR (95% confidence interval [CI]) was 40% (16, 68) for CC2, 25% (12, 42) for MC1, 17% (4, 41) for CC1. 6 month (mo) PFS rate (95% CI) was 80% (50, 93) for CC2, 33% (16, 50) for MC1, 29% for CC1 (10, 52). Except for CC2 6 mo PFS rate data are not mature. PD-L1 was evenly distributed across TIS^vopra pts but not associated with efficacy. Study treatment was well tolerated with 7.2% of pts reporting Grade ≥3 treatment related adverse events (TRAEs). Most common TRAEs were Grade 1/2 hyperthyroidism, hypothyroidism, rash. The pulsatile pattern of V 0.03 mg showed shorter duration of TE vs 0.1 mg.

Conclusions

P +/- V was well tolerated. The 1° endpoint was not met. P+V 0.03 mg/kg trends toward improved clinical benefit in 1° and 2° endpoints and responses are durable. P is active and continues to be used in combination trials. Shorter TE duration of V 0.03 mg/kg may contribute to clinical activity.

Clinical trial identification

NCT04549025.

Legal entity responsible for the study

Jounce Therapeutics, Inc.

Funding

Jounce Therapeutics, Inc.

Disclosure

M. Gumus: Financial Interests, Institutional, Invited Speaker: Pfizer, Gen Pharmaceuticals, Novartis, Bayer, Amgen, Jounce Therapeutics; Financial Interests, Institutional, Advisory Board: Amgen, Roche, BMS, Astra-Zeneca. A. Sukalinskaya: Financial Interests, Institutional, Invited Speaker: Jounce Therapeutics. Z.G. Andric: Financial Interests, Personal, Invited Speaker: MSD, Roche, AstraZeneca, Novartis, Merck-D. V. Cheshuk: Financial Interests, Personal, Principal Investigator: Jounce Therapeutics. T. Ciuleanu: Financial Interests, Institutional, Other, Principal Investigator: Jounce Therapeutics. S. Sezgin Goksu: Financial Interests, Personal, Advisory Board: Novartis, MSD; Financial Interests, Personal, Invited Speaker: Novartis, Roche, Phizer, BMS, MSD; Financial Interests, Personal and Institutional, Invited Speaker: BMS, MSD, Lilly, Roche, Jounce Therapatics. T. Cil: Financial Interests, Institutional, Invited Speaker: Jounce Therapeutics. I. Cicin: Other, Personal, Other, Principal investigator for Jounce Therapeutic: Jounce Therapeutic. I.V. Bulat: Financial Interests, Personal and Institutional, Invited Speaker: Jounce Therapeutics. Y.V. Ostapenko: Financial Interests, Institutional, Other, Principal Investigator: Jounce Therapeutics. K.D. Penkov: Financial Interests, Personal, Advisory Board: Nektar terapeutics; Financial Interests, Personal and Institutional, Invited Speaker: AbbVie, AstraZeneca, Pfizer, Jounce Terapeutics, Polyphor, GSK, Mabscale, Biocad, Sanofi, Novartis. C. Hart: Financial Interests, Personal, Full or part-time Employment: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares, Shareholder: Jounce Therapeutics. M. Lai: Financial Interests, Personal, Full or part-time Employment: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares: Jounce Therapeutics. B. Chaao: Financial Interests, Personal, Full or part-time Employment: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares, Shareholder: Jounce Therapeutics. J. Jimenez: Financial Interests, Personal, Full or part-time Employment: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares, Shareholder: Jounce Therapeutics. A. Sepahi: Financial Interests, Personal, Full or part-time Employment: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares, Shareholder: Jounce Therapeutics. G. Shi: Financial Interests, Personal, Full or part-time Employment: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares, Shareholder: Jounce Therapeutics. S. Trott: Financial Interests, Personal, Full or part-time Employment: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares, Shareholder: Jounce Therapeutics. E. Hooper: Financial Interests, Personal, Other, Full time employee of Jounce; have spoken at public events regarding Jounce related programs: Jounce Therapeutics; Financial Interests, Personal, Full or part-time Employment, Sr. Medical Director at Jounce: Jounce Therapeutics; Financial Interests, Personal, Stocks/Shares, Owner of Jounce stock as a benefit of full time employment: Jounce Therapeutics.