Sintilimab Plus Bevacizumab Biosimilar Injection Yields Improved PFS in nsqNSCLC

Patients with EGFR-mutated non-squamous non–small cell lung cancer who progressed following EGFR-TKI therapy experienced a progression-free survival benefit following treatment with sintilimab plus a bevacizumab biosimilar injection and chemotherapy.

Improved progression-free survival (PFS) was observed among patients treated with sintilimab (Tyvyt) plus a bevacizumab (Avastin) biosimilar injection (Byvasda) combined with pemetrexed and cisplatin in patients with EGFR-mutated non-squamous non–small cell lung cancer (nsqNSCLC) and who progressed after EGFR-TKI therapy, according to the first interim analysis results of the phase 3 ORIENT-31 (NCT03802240) trial at the 2021 European Society for Medical Oncology Virtual Plenary.

Patients in arm A who received sintilimab plus the bevacizumab biosimilar injection and chemotherapy had a better PFS compared with Arm C in which patients received only chemotherapy (HR, 0.464; 95% CI, 0.337-0.639; P <.0001). The median PFS in arm A was 6.9 months (95% CI, 6.0-9.3) compared with 4.3 months (95% CI, 4.1-5.4) arm C . Patients in arm A also experienced better overall response rate (ORR) and duration of response vs arm C.

"Despite initial clinical response to EGFR-TKI, virtually all advanced EGFR-mutated NSCLC inevitably acquire resistance mechanisms and progress after treatment with an EGFR-TKI. For those patients with EGFR-mutated advanced nsqNSCLC who have progressed following EGFR-TKI treatment, platinum-based chemotherapy is the current standard of care, but with limited benefit. New treatment options are imperative for this unmet medical need,” Shun Lu, a professor of the Oncology Department at Shanghai Chest Hospital, said in the press release.

A total of 444 patients were enrolled in the double-blind multi-center ORIENT-31 study and were randomized 1:1:1 to receive either sintilimab plus chemotherapy with the bevacizumab biosimilar injection, sintilimab and placebo plus chemotherapy, or placebo plus chemotherapy. Patients were eligible for treatment if they had disease progression following a first- or second-generation EGFR TKI, were confirmed as being T790M negative or T790M positive, or experienced disease progression following a third generation EGFR TKI as first-line treatment.

After undergoing 4 cycles of treatment with the combination, patients were to receive maintenance treatment that consisted of sintilimab plus bevacizumab biosimilar injection and pemetrexed, sintilimab plus placebo 2 and pemetrexed, or placebo 1 plus placebo 2 and pemetrexed. Patients were to continue this treatment until they experienced radiographic disease progression, unacceptable toxicity, or other conditions that required discontinuation.

In the first arm, patients received 200 mg of sintilimab, 15 mg/kg of the biosimilar, 500 mg/m2 of pemetrexed, and 75 mg/m2 of cisplatin intravenously every 3 weeks. In arm 2, patients received a combination of sintilimab with pemetrexed, cisplatin, and a placebo every 3 weeks. The active comparator arm was given pemetrexed, cisplatin, and the 2 placebos administered every 3 weeks.

The FDA has accepted a biologics license application for sintilimab in combination with pemetrexed and platinum chemotherapy for first line treatment of nsqNSCLC.


Innovent releases the ORIENT-31 phase 3 study first interim analysis results of sintilimab plus Byvasda (bevacizumab biosimilar injection) and chemotherapy in patients with EGFR-mutated nonsquamous non-small cell lung cancer who progressed after EGFR-TKI therapy at ESMO Virtual Plenary 2021. News release. November 21, 2021. Accessed November 22, 2021.