57O Randomized double-blind phase II trial (PERLA) of dostarlimab (dostar) + chemotherapy (CT) vs pembrolizumab (pembro) + CT in metastatic non-squamous NSCLC: Primary results

PD-(L)1 inhibitors have a prominent role in the treatment (tx) of NSCLC, with pembro a commonly used agent, but with no direct comparisons between inhibitors to date. This global, randomized, Phase II double-blind study (PERLA; NCT04581824) compared the efficacy and safety of dostar + CT versus pembro + CT in patients (pts) with first-line (1L) metastatic non-squamous NSCLC. Pts with no known EGFR, ALK or other genomic aberrations actionable locally by targeted therapies, known PD-L1 status, ECOG PS 0–1, and no prior systemic tx for metastatic NSCLC were randomized 1:1 to dostar 500 mg or pembro 200 mg Q3W IV ≤35 cycles, both in combination with CT (4 cycles pemetrexed [pem; 500 mg/m2] + carboplatin [AUC 5 mg/mL/min] or cisplatin [75 mg/m2] then pem up to cycle 35) Q3W IV. Primary endpoint was ORR by BICR (RECIST V1.1; difference by Mantel and Haenszel test and Sato's variance estimator; point estimates by Clopper-Pearson). Safety was a secondary endpoint. Disease assessments were at wks 6 & 12, then every 9 wks x4, then every 12 wks. 121 and 122 pts in the dostar + CT and pembro + CT arms were treated and evaluable, respectively; 41% and 42% had PD-L1 TPS <1; 36% had TPS 1–49% and 22% had TPS ≥50 in both arms. ORR was 46% for dostar + CT, with 2 complete responses [CRs] (2%) and 54 partial responses [PRs] (45%); ORR was 37% for pembro + CT, with 3 CRs (2%) and 42 PRs (34%) (9.3% difference [95% CI: −2.7–21.3]). Safety is shown in the table. Additional analyses (inc. PFS [secondary endpoint], PD-L1 sub-analyses and DOR [exploratory]) will be presented.Table: 57On, (%)Dostar + CT (n=121)Pembro + CT (n=122)TEAEs Grade ≥3 Serious Leading to any tx-discontinuation* Leading to dostar/pembro tx-discontinuation* Leading to death117 (97) 71 (59) 46 (38) 30 (25) 18 (15) 15 (12)118 (97) 73 (60) 54 (44) 39 (32) 29 (24) 12 (10)∗Permanent tx-discontinuation. TEAE, treatment-emergent adverse event Open table in a new tab ∗Permanent tx-discontinuation. TEAE, treatment-emergent adverse event In this first randomized phase II study to directly compare PD-1 inhibitors, dostar + CT showed comparable efficacy to pembro + CT in 1L metastatic non-squamous non-oncogenic NSCLC. Safety profiles were similar and consistent with published data.