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Abstract
VP9-2021: ORIENT-31: Phase III study of sintilimab with or without IBI305 plus chemotherapy in patients with EGFR mutated nonsquamous NSCLC who progressed after EGFR-TKI therapy
Authors: S. Lu, L. Wu, H. Jian, Y. Pan, F. Ye, A. Liu
Published: 19 November 2021 DOI: https://doi.org/10.1016/j.annonc.2021.10.007
Background
Treatment option for nonsquamous non-small cell lung cancer (nsqNSCLC) with epidermal growth factor receptor mutations (EGFRm) is limited upon progression after tyrosine kinase inhibitors (TKIs). ORIENT-31 is a randomized, double-blind, phase 3 study of sintilimab (sint, anti-PD-1 antibody) with or without IBI305 (bevacizumab biosimilar) plus chemotherapy (chemo) in patients (pts) with EGFRm nsqNSCLC who progressed after EGFR TKI therapy (NCT03802240).
Methods
Pts with EGFRm nsqNSCLC who had progressed afterEGFR-TKI therapy were randomized (1:1:1) to Arm A (sint + IBI305 + chemo), Arm B [sint + placebo 2 (pb2) + chemo] or Arm C (pb1 + pb2 + chemo), stratified by sex (male vs female) and brain metastasis (yes vs no). Sint / pb1 (200 mg), IBI305 / pb2 (15 mg/kg), pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) were administered IV Q3W for 4 cycles, followed by maintenance treatment of sint / pb1, IBI305 / pb2 and pemetrexed. Conditional crossover to sint monotherapy was allowed for pts in Arm C. Primary endpoint is progression-free survival (PFS) by independent radiographic review committee (IRRC).
Results
By data cutoff (31 Jul, 2021, median follow up of 9.8m) of first interim analysis, 444 pts were randomized (Arm A / B / C 148 / 145 / 151). Median age was 57 y. 36.0% pts had brain metastasis. Previously, 63.7% pts received 1st or 2nd generation (G) TKI with T790M-, 28.2% pts received 1st or 2nd and then 3rd G TKI with T790M+, 8.1% pts received first-line 3rd G TKI. Median PFS (95%CI) by IRRC was 6.9m (6.0, 9.3) in Arm A, 5.6m (4.7, 6.9) in Arm B, 4.3m (4.1, 5.4) in Arm C. PFS was significantly prolonged in Arm A vs. Arm C (HR 0.464, 95%CI: 0.337, 0.639; p<0.0001). Arm B showed trend of PFS benefit vs. Arm C (HR 0.750, 95%CI: 0.555, 1.013; p=0.0584). The futility analysis of Arm A vs. B did not cross the futility boundary (HR 0.726, 95%CI: 0.528, 0.998). Confirmed ORR were 43.9%, 33.1% and 25.2% in Arm A, B and C respectively. Incidence of grade ≥3 treatment-emergent AEs were 54.7%, 39.3% and 51.0% respectively.
Conclusions
In pts with EGFRm nsqNSCLC who progressed after EGFR-TKIs, sint combined with IBI305 and chemo has significantly improved PFS compared with chemo alone.
