Welcome back 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’ll provide a quick update on two recent FDA cancer drug approvals.
On March 18, 2022, the FDA approved nivolumab and relatlimab-rmbw (brand name Opdualag) for adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma. Opdualag is a fixed-dose combination of the LAG-3-blocking antibody relatlimab and the programmed death receptor-1 blocking antibody nivolumab.
Efficacy was evaluated in RELATIVITY-047, a randomized 1:1, double-blinded trial in 714 patients with previously untreated metastatic or unresectable Stage III or IV melanoma. The trial excluded patients with active autoimmune disease, medical conditions requiring systemic treatment with moderate or high dose corticosteroids or immunosuppressive medications, uveal melanoma, and active or untreated brain or leptomeningeal metastases.
The major efficacy outcome measure was progression-free survival determined by Blinded Independent Central Review using RECIST v1.1. The trial demonstrated a statistically significant improvement in progression-free survival by Blinded Independent Central Review for Opdualag compared to nivolumab. Median progression-free survival was 10.1 months in the Opdualag arm and 4.6 months in the nivolumab arm. An additional efficacy outcome measure was overall survival. The final analysis of overall survival was not statistically significant with median overall survival not reached in the Opdualag arm and 34.1 months in the nivolumab arm.
The most common adverse reactions reported in more than 20% of patients were musculoskeletal pain, fatigue, rash, pruritus, and diarrhea. The most common laboratory abnormalities reported in more than 20% were decreased hemoglobin, decreased lymphocytes, increased AST, increased ALT, and decreased sodium.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The application reviews may be ongoing at the other regulatory agencies.
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 March 21, 2022, the FDA approved pembrolizumab (brand name Keytruda), as a single agent, for patients with advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation.
The FDA also approved the VENTANA MMR RxDx Panel as a companion diagnostic device to select patients with mismatch repair deficient in solid tumors that are eligible for treatment with pembrolizumab. The FDA previously approved the FoundationOne CDx as a companion diagnostic device to select patients with microsatellite instability-high in solid tumors that are eligible for treatment with pembrolizumab.
Efficacy was evaluated in KEYNOTE-158, a multicenter, non-randomized, open-label, multi-cohort trial in 90 patients with unresectable or metastatic microsatellite instability-high or mismatch repair deficient endometrial carcinoma in Cohorts D and K. Microsatellite instability or mismatch repair tumor status was determined using polymerase chain reaction or immunohistochemistry, respectively.
The major efficacy outcome measures were objective response rate and duration of response as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Objective response rate was 46%. Median duration of response was not reached, with 68% having response durations of more than 12 months and 44% having response durations of more than 24 months.
The most common adverse reactions reported in more than 20% of patients were fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritis, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism. Immune-mediated side effects are also associated with pembrolizumab; these include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse 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 www.fda.gov/drugsatFDA.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting Program at www.fda.gov/medwatch.
Follow the Division of Drug Information on Twitter @FDA_Drug_Info and the Oncology Center of Excellence @FDAOncology. Send your feedback via email to FDAOncology@fda.hhs.gov. Thanks for tuning into the D.I.S.C.O. Burst Edition.