Welcome to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we have another update on two recent FDA cancer drug approvals.
On April 22, 2021, FDA granted accelerated approval to dostarlimab-gxly (brand name Jemperli) for adult patients with mismatch repair deficient recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a prior platinum-containing regimen.
Efficacy was evaluated based on cohort A1 in the GARNET Trial, a multicenter, multicohort, open-label trial in patients with advanced solid tumors. The efficacy population consisted of 71 patients with mismatch repair deficient recurrent or advanced endometrial cancer who progressed on or after a platinum-containing regimen.
The main efficacy endpoints were overall response rate and duration of response, as assessed by blinded independent central review according to RECIST 1.1. Confirmed overall response rate was 42.3%. The complete response rate was 12.7% and partial response rate was 29.6%. Median duration of response was not reached, with 93.3% of patients having durations longer than 6 months.
Serious adverse reactions reported in more than 2% of patients included sepsis, acute kidney injury, urinary tract infection, abdominal pain, and pyrexia. The most common adverse reactions reported in more than 20% of patients were fatigue/asthenia, nausea, diarrhea, anemia, and constipation. The most common grade 3 or 4 adverse reactions occurring in more than 2% of patients were anemia and increase in transaminases. Immune-mediated adverse reactions can occur including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
FDA also approved the VENTANA MMR RxDx Panel as a companion diagnostic device for selecting endometrial cancer patients for treatment with dostarlimab-gxly.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
On April 23, 2021, FDA granted accelerated approval to loncastuximab tesirine-lpyl (brand name Zynlonta), a CD19-directed antibody and alkylating agent conjugate, for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma arising from low grade lymphoma, and high-grade B-cell lymphoma.
Approval was based on LOTIS-2, an open-label, single-arm trial in 145 adult patients with relapsed or refractory diffuse large B-cell lymphoma or high-grade B-cell lymphoma after at least two prior systemic regimens. Patients received treatment until progressive disease or unacceptable toxicity.
The main efficacy outcome measure was overall response rate, as assessed by an independent review committee using Lugano 2014 criteria. The overall response rate was 48.3% with a complete response rate of 24.1%. After a median follow-up of 7.3 months, median response duration was 10.3 months. Of the 70 patients who achieved objective responses, 36% were censored for response duration prior to 3 months.
The prescribing information provides warnings and precautions for adverse reactions including edema and effusions, myelosuppression, infections, and cutaneous reactions.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Full prescribing information for these approvals can be found on the web at Drugs@FDA: FDA-Approved Drugs.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting System at MedWatch.
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