The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Eli Lilly and Company regarding the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of patients with nonsquamous non-small cell lung cancer (NSCLC).

Sintilimab is an investigational programmed death receptor-1 (PD-1) inhibitor. The BLA submission included data from the randomized, double-blind, phase 3 ORIENT-11 trial (ClinicalTrials.gov Identifier: NCT03607539) in 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC. Patients were randomly assigned 2:1 to receive sintilimab plus pemetrexed and platinum chemotherapy (n=266) or placebo plus pemetrexed and platinum chemotherapy (n=131). 

Based on the primary analysis of PFS with a data cut-off date of November 15, 2019, the median PFS was significantly improved in the combination arm compared with the placebo arm (8.9 months vs 5.0 months, respectively; hazard ratio [HR], 0.48; 95% CI, 0.36-0.66; P =.0000004). Moreover, based on a secondary analysis of OS with a data cut-off date of January 15, 2021, the median OS was not reached in the combination arm compared with 16.8 months in the placebo arm (HR, 0.60; 95% CI, 0.45-0.79; P =.0003). The median OS was not reached in the combination arm compared with 16.8 months in the placebo arm (HR, 0.60; 95% CI, 0.45-0.79; P =.0003).

Additionally, the combination arm demonstrated a significant improvement in PFS in patients with high or medium immune cell infiltration compared with the placebo arm. There was no additional benefit in patients with low or absent immune cell infiltration.

The CRL is consistent with the Oncology Drug Advisory Committee’s (ODAC) vote against the approval of sintilimab in February 2022. In the letter, the FDA recommended that the Company conduct a multiregional clinical trial comparing standard of care therapy for first line metastatic NSCLC to sintilimab with chemotherapy using a noninferiority design with an OS endpoint.

References

  1. Lilly announces Complete Response Letter 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. Eli Lilly and Company. Accessed March 24, 2022. https://www.prnewswire.com/news-releases/lilly-announces-complete-response-letter-for-sintilimab-in-combination-with-pemetrexed-and-platinum-chemotherapy-for-the-first-line-treatment-of-people-with-nonsquamous-non-small-cell-lung-cancer-301509537.html
  2. FDA advisory committee votes to recommend additional data for sintilimab submission. News release. Innovent Biologics. February 10, 2022. Accessed March 24, 2022. https://www.prnewswire.com/news-releases/fda-advisory-committee-votes-to-recommend-additional-data-for-sintilimab-submission-301480399.html
  3. FDA Briefing Document – Oncologic Drugs Advisory Committee Meeting. BLA 761222: Sintilimab; Innovent Biologics (Suzhou) Co., Ltd. February 10, 2022. Accessed March 25, 2022. https://www.fda.gov/media/156021/download