Recently, the U.S. Food and Drug Administration (FDA) granted Priority Review to zanubrutinib in pretreated patients with marginal zone lymphoma, and accepted a biologics license application for sintilimab injection in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non–small cell lung cancer.
Priority Review for Zanubrutinib in Marginal Zone Lymphoma
The FDA has accepted a supplemental new drug application and granted Priority Review to zanubrutinib for the treatment of adult patients with marginal zone lymphoma who have received at least one prior anti–CD20-based therapy. The Prescription Drug User Fee Act target action date is September 19, 2021.
Zanubrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK). Because new BTK is continuously synthesized, zanubrutinib was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, zanubrutinib has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.
Clinical data in the regulatory submission include results from the single-arm, open-label, multicenter, phase II MAGNOLIA trial (ClinicalTrials.gov identifier NCT03846427) in patients with relapsed or refractory marginal zone lymphoma presented at the American Society of Hematology Annual Meeting & Exposition in December 2020 (Abstract 339), with supportive data from a global phase I/II trial (ClinicalTrials.gov identifier NCT02343120) in patients with B-cell malignancies. The submission also includes pooled safety data from 847 patients with B-cell malignancies treated with zanubrutinib in seven clinical trials.
Biologics License Application Accepted for Sintilimab in Combination With Pemetrexed and Platinum Chemotherapy for the First-Line Treatment of Nonsquamous NSCLC
The FDA accepted for review a biologics license application for sintilimab injection in combination with pemetrexed and platinum chemotherapy for the first-line treatment of people with nonsquamous non–small cell lung cancer (NSCLC). The Prescription Drug User Fee Act goal date is in March 2022.
This is the first U.S. regulatory submission of sintilimab, a PD-1 inhibitor. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T cells, blocks the PD-1/PD-L1 pathway, and reactivates T cells to kill cancer cells.
Sintilimab is currently being evaluated in a wide variety of cancer types under a broad clinical development program. To date, sintilimab has two indications approved in China, three regulatory submissions under review in China, and this regulatory application under review in United States. This regulatory application was submitted to the FDA in March 2021, primarily based on the results of the phase III ORIENT-11 trial.
ORIENT-11 is a randomized, double-blind, phase III clinical trial assessing the efficacy and safety of sintilimab in combination with pemetrexed and platinum chemotherapy compared to placebo in combination with pemetrexed and platinum chemotherapy as a first-line treatment for patients with advanced or metastatic nonsquamous NSCLC with no sensitizing EGFR mutations or ALK rearrangements. The primary endpoint is progression-free survival as assessed by an independent radiographic review committee based on Response Evaluation Criteria in Solid Tumors version 1.1; secondary endpoints include overall survival and safety.
A total of 397 patients were enrolled and randomly assigned 2:1 to receive either sintilimab at 200 mg or placebo in combination with pemetrexed and platinum chemotherapy every 3 weeks for up to four cycles, followed by either sintilimab or placebo plus pemetrexed maintenance therapy. Patients received treatment until radiographic disease progression, unacceptable toxicity, or any other conditions that required treatment discontinuation. Conditional crossover was permitted. The results of the ORIENT-11 study were published in 2020.
In China, sintilimab has been approved for: