Sintilimab Meets Primary End Point in ORIENT-31 Trial for EGFR+ Non-Squamous NSCLC

Sintilimab (Tyvyt) has yielded a promising improvement to progression-free survival (PFS) in patients with EGFR-mutant nonsquamous non–small cell lung cancer (nsqNSCLC) who have previously been treated with an EGFR tyrosine kinase inhibitor (TKI), according to the first interim analysis of the phase 3 ORIENT-31 trial (NCT03802240).

These data, which were made available after review by an independent data monitoring committee, revealed that patients within the intent-to-treat population experienced a statistically significant and clinically meaningful PFS benefit after being treated with sintilimab and a bevacizumab biosimilar injection (Byvasda) vs chemotherapy alone. Additionally, when combined with chemotherapy, sintilimab yielded a trend toward PFS benefit compared with chemotherapy alone, although investigators noted that the findings are not yet mature.

Findings from ORIENT-31 will be presented at an upcoming meeting, investigators stated.

“For 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 treatments are clearly imperative. ORIENT-31 is the first prospective, double-blind phase 3 study worldwide to demonstrate significant PFS benefit with an anti–PD-1 antibody combination therapy in this patient population. It has shown the clinical value of adding sintilimab plus Byvasda (bevacizumab biosimilar injection) to platinum chemotherapy. This quadruple regimen has the potential to bring forth a new and more effective treatment option to patients with EGFR-mutated nsqNSCLC following treatment with an EGFR TKI,” Shun Lu, a professor of the Oncology Department of Shanghai Chest Hospital and principal investigator of the study, said in a press release.

The global, double-blind, multicenter trial examined the use sintilimab, with or without a bevacizumab biosimilar injection, combined with chemotherapy in patients with EGFR-mutant disease that had progressed following treatment with an EGFR TKI. The trial had an estimated enrollment of 600 patients who received 1 of several regimens.

The first arm received 200 mg of intravenous sintilimab plus 15 mg/kg of the biosimilar, 75 mg/m2 of cisplatin every 3 weeks, and 500 mg/m2 of pemetrexed. The second arm combined the sintilimab backbone with pemetrexed, cisplatin, and placebo every 3 weeks. In the active comparator arm, patients were administered pemetrexed and cisplatin plus 2 placebos every 3 weeks.

The study’s secondary outcome measures include overall survival and overall response rate.

In order to enroll on the trial, patients were required to be 18 years of age or older and younger than 75 years with histologically or cytologically confirmed stage IIIB or IIIC disease that is not eligible for resection or radical concurrent chemoradiotherapy. Patients also needed to have an EGFR-mutated tumor confirmed via tumor histology or cytology, resistance to an EGFR TKI, and an ECOG performance status of 0 or 1.

Findings from the prespecified PFS futility analysis, which examined sintilimab plus the bevacizumab biosimilar injection and chemotherapy vs sintilimab and chemotherapy, indicated that the regimen did not cross the futility stopping boundary. Moreover, investigators identified a numerical benefit by combining the biosimilar with sintilimab and chemotherapy with no additional toxicities.

Reference

Innovent announces ORIENT-31, a phase 3 study of sintilimab in patients with EGFR-mutated nonsquamous non-small cell lung cancer with prior EGFR-TKI treatment, has met primary endpoint. News release. Innovent Biologics, Inc. October 17, 2021. Accessed October 18, 2021. https://bit.ly/3BRKWeI