LBA58 - Sintilimab with or without IBI305 plus chemotherapy in patients with EGFR mutated non-squamous non-small cell lung cancer (EGFRm nsqNSCLC) who progressed on EGFR tyrosine-kinase inhibitors (TKIs) therapy: Second interim analysis of phase III ORIENT-31 study

Background

The randomized, double-blind, phase 3 ORIENT-31 study was to evaluate sintilimab (sin, anti-PD-1 antibody) with or without IBI305 (bevacizumab biosimilar) plus chemotherapy (chemo), vs chemo, in patients (pts) with EGFRm nsqNSCLC who progressed on EGFR TKIs therapy. The first interim analysis (IA) showed sin + IBI305 + chemo significantly improved progression-free survival (PFS) vs chemo alone (Lu, et al. Lancet Oncol 2022).

Methods

Eligible pts were randomized (1:1:1 at the first stage and 2:2:1 at the second stage) into Arm A (sin + IBI305 + chemo), Arm B (sin + placebo [pb] 2 + chemo) and Arm C (pb1 + pb2 + chemo). Sin/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 sin/pb1, IBI305/pb2 and pemetrexed. The primary endpoint was PFS assessed by IRRC per RECIST v1.1. Per prespecified statistical analysis plan, the second IA (reported here) aimed to evaluate the PFS between Arm B and Arm C, and the superiority conclusion of Arm A over Arm C has been achieved at the first IA.

Results

By data cutoff (Mar 31, 2022), 476 pts were randomized (Arm A/B/C: 158/158/160). Median age was 57.0 years. 37.0% pts had brain metastasis. Previously, 63.0% pts received 1st or 2nd generation (G) TKI with T790M-, 26.3% pts received 1st or 2nd and then 3rd G TKI with T790M+, and 10.5% pts received first-line 3rd G TKI. With a median follow-up of 13.1 months, median PFS (95% CI) by IRRC was 7.2 months (6.6, 9.3) in Arm A, 5.5 months (4.5, 6.1) in Arm B, and 4.3 months (4.1, 5.3) in Arm C. PFS was significantly improved in Arm B vs Arm C (HR 0.723, 95% CI: 0.552, 0.948; P=0.0181). Confirmed ORR by IRRC was 48.1%, 34.8% and 29.4% in Arm A, B and C respectively; DCR was 86.1%, 81.6% vs 75.6%; median DOR was 8.5 months, 7.4 months vs 5.7 months. Grade ≥3 treatment-emergent adverse events occurred in 59.5%, 46.2%, and 56.9% pts respectively.

Conclusions

Sin combined with or without IBI305 and chemo significantly improved PFS in pts with advanced EGFRm nsqNSCLC who progressed on EGFR-TKI therapy, vs chemo alone.

Clinical trial identification

NCT03802240.

Editorial acknowledgement

Legal entity responsible for the study

Innovent Biologics, Inc., Suzhou, China.

Funding

Innovent Biologics, Inc., Suzhou, China.

Disclosure

S. Lu: Financial Interests, Personal, Funding: Innovent Biologics (Suzhou) Co., Ltd.; Financial Interests, Institutional, Funding: National Natural Science Foundation of China; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Hengrui Therapeutics, Beigene, Hansoh, Roche, Lilly Suzhou Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, consulting fee: AstraZeneca, Ptizer, BoehringerIngelheim, Hutchison, Zailab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co. Ltd., Roche. L. Wu: Financial Interests, Personal, Funding: Innovent Biologics (Suzhou) Co., Ltd.; Financial Interests, Personal, Research Grant: AstraZeneca, BMS, HengRui. H. Jian: Financial Interests, Personal, Funding: Innovent Biologics (Suzhou) Co., Ltd.. All other authors have declared no conflicts of interest.