Sintilimab Moves Forward With FDA Acceptance of Application in Nonsquamous NSCLC

Based on results of a phase 3 trial demonstrating the superiority of sintilimab versus placebo plus chemotherapy for nonsquamous non–small cell lung cancer, the FDA considers approval of the PD-1 inhibitor injection.

A biologics license application for sintilimab in combination with pemetrexed and platinum-based chemotherapy to treat patients with nonsquamous non–small cell lung cancer (NSCLC) in the first line was accepted by the FDA, according to an announcement released jointly by Innovent Biologics, Inc. and Eli Lilly and Company.1

The application is the first regulatory submission of the fully human IgG4 monoclonal antibody PD-1 inhibitor and is based on data from the phase 3 ORIENT-11 trial (NCT03607539) comparing sintilimab versus placebo plus pemetrexed/platinum.

“The acceptance of this application—the first for sintilimab in the U.S. and outside of China—is an important milestone in Innovent’s global commercialization strategy and in our collaboration with Lilly,” Yongjun Liu, MD, PhD, president of Innovent, said in a press release. “We look forward to working closely with the FDA to potentially bring this sintilimab-pemetrexed-platinum chemotherapy combination as a treatment option in the U.S., following the regimen’s regulatory approval in China earlier this year.”

Data from the trial were presented in August 2020 at the International Association for the Study of Lung Cancer’s World Conference on Lung Cancer Virtual Presidential Symposium and published in the Journal of Thoracic Oncology. Patients with locally advanced or metastatic nonsquamous NSCLC treated with active therapy showed a significant increase in median progression-free survival (PFS) versus control therapy, at 8.9 months (95% CI, 7.1-11.3) and 5.0 months (95% CI, 4.8-6.2), respectively (HR, 0.482; 95% CI, 0.362-0.643; P <.00001).

When patients were stratified by PD-L1 per tumor proportion score (TPS), PFS increased in step with higher expression. Those with TPS less than 1% had a median PFS of 7.3 month (95% CI, 6.2-not reached [NR]) with sintilimab versus 5.1 months (95% CI, 4.6-7.8) with placebo (HR, 0.664; 95% CI, 0.406-1.086). For those with PD-L1 TPS between 1% to 49%, the corresponding medians were 7.1 months (95% CI, 6.2-9.2) and 4.8 months (95% CI, 2.5-8.0), respectively (HR, 0.503; 95% CI, 6.2-9.2). With PD-L1 TPS 50% or higher, the median PFS was NR (95% CI, 9.2-NR) with sintilimab and 5.0 months (95% CI, 4.3-6.8) without (HR, 0.310; 95% CI, 0.197-0.489).

Patients receiving sintilimab had an objective response rate of 51.9%, which included 1.1% complete responses versus 29.8% and 0%, respectively, with placebo. The disease control rate for sintilimab was 86.8% and 75.6% with placebo. Median response duration for each was NR (95% CI, 8.0-NR) and 5.5 months (95% CI, 4.1-10.9), respectively.

Patients must have had stage IIIB/C or IV disease that was ineligible for surgery or local therapy, an ECOG performance status of 0 or 1, and a tumor sample available for PD-L1 assessment to be enrolled. Patients were stratified by gender, type of platinum therapy (cisplatin vs carboplatin), and PD-L1 expression level. The primary end point was PFS by independent radiologic review committee.

Patients were randomized in a 2:1 fashion to receive either sintilimab at 200 mg (n = 266) every 3 weeks for up to 2 years or placebo (n = 131) plus pemetrexed at 500 mg/m2 every 3 weeks and cisplatin at 75 mg/m2 or carboplatin area under the curve 5 every 3 weeks for 4 cycles.

The adverse effect (AEs) profile was similar between arms, with grade 3 or greater events occurring in 61.7% of patients receiving sintilimab versus 58.5% of those on placebo. Serious AEs occurred in 28.2% and 29.8% of patients, respectively.

“We are pleased the sintilimab submission is progressing. Our pursuit of this proposed indication in the U.S. reinforces Lilly’s and Innovent’s joint commitment to offer additional therapeutic options for people living with lung cancer and the healthcare providers who treat them,” Anne White, president of Lilly Oncology, said in a press release. “This is an encouraging start for our collaborative efforts to make sintilimab available in countries beyond China, as we continue to pursue opportunities globally for this immuno-oncology medicine across various tumor types.”

The Prescription Drug User Fee Act date for the application is set for March 2022.


1. U.S. FDA Accepts Regulatory Submission for Sintilimab in Combination with Pemetrexed and Platinum Chemotherapy for the First-Line Treatment of People with Nonsquamous Non-Small Cell Lung Cancer. News release. Innovent Biologics, Inc. and Eli Lilly and Company. May 18, 2021. Accessed May 18, 2021.

2. Yang Y, Wang Z, Fang J, et al. Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11). J Thorac Oncol. 2020;15(10):1636-1646. doi:10.1016/j.jtho.2020.07.014