Recently, the U.S. Food and Drug Administration (FDA) granted Priority Review to treatments for KRAS G12C–mutated non–small cell lung cancer (NSCLC) and high-risk, bacillus Calmette-Guérin–unresponsive non–muscle-invasive bladder cancer. A new drug application for a therapy for Waldenström’s macroglobulinemia was also accepted.
Priority Review for Sotorasib in KRAS G12C–Mutated Locally Advanced or Metastatic NSCLC
The FDA granted Priority Review to sotorasib for the treatment of patients with KRAS G12C–mutated locally advanced or metastatic NSCLC, following at least one prior systemic therapy. The Prescription Drug User Fee Action date for sotorasib is August 16, 2021. Sotorasib is a KRAS G12C inhibitor.
The new drug application is based on phase II results from the CodeBreaK 100 clinical trial that studied patients with locally advanced or metastatic NSCLC whose cancer had progressed despite treatment with chemotherapy and/or immunotherapy. Full results from the study were recently presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC).
CodeBreaK 100, the phase II, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C–mutant solid tumors. Eligible patients must have received a prior line of systemic anticancer therapy consistent with their tumor type and stage of disease. The primary endpoint for the study was centrally assessed objective response rate. The phase II trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by Response Evaluation Criteria in Solid Tumors at baseline.
Priority Review for Vicineum in High-Risk, BCG-Unresponsive, Non–Muscle-Invasive Bladder Cancer
The FDA accepted a biologics license application for Vicineum for the treatment of high-risk, bacillus Calmette-Guérin (BCG)-unresponsive, non–muscle-invasive bladder cancer and granted the application Priority Review. The anticipated target Prescription Drug User Fee Act date for a decision is August 18, 2021.
Vicineum is a locally administered fusion protein, comprising a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas exotoxin A. Vicineum is constructed with a stable, genetically engineered peptide tether to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical trials, EpCAM has been shown to be overexpressed in non–muscle-invasive bladder cancer cells, with minimal to no EpCAM expression observed on normal bladder cells.
Supplemental New Drug Application for Zanubrutinib in Waldenström’s Macroglobulinemia
The FDA has accepted a supplemental new drug application for zanubrutinib for the treatment of adult patients with Waldenström’s macroglobulinemia. The Prescription Drug User Fee Act target action date is October 18, 2021. Zanubrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase.
The application, which includes data from 351 patients with Waldenström’s macroglobulinemia, was primarily based on safety and efficacy data from the global phase III ASPEN trial of zanubrutinib compared to ibrutinib for the treatment of Waldenström’s macroglobulinemia, with supportive data from a pivotal phase II trial of zanubrutinib in relapsed/refractory Waldenström’s macroglobulinemia conducted in China and a global phase I/II trial in patients with B-cell malignancies. In addition, safety data from 779 patients in six clinical trials of zanubrutinib were included in the submission.
