On September 17, 2024, the Food and Drug Administration approved pembrolizumab (Keytruda, Merck) with pemetrexed and platinum chemotherapy as first-line treatment of unresectable advanced or metastatic malignant pleural mesothelioma (MPM).
Full prescribing information for Keytruda will be posted on Drugs@FDA.
Efficacy and Safety
Efficacy was investigated in KEYNOTE-483 (NCT02784171), a randomized, open-label trial in patients with unresectable advanced or metastatic MPM and no prior systemic therapy for advanced/metastatic disease. Patients were randomized (1:1) to receive either pembrolizumab for up to 2 years in combination with pemetrexed and platinum-based chemotherapy for up to 6 cycles (n=222) or pemetrexed and platinum-based chemotherapy for up to 6 cycles (n=218).
The main efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures were progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR), as assessed by blinded independent central review, according to modified RECIST 1.1 for mesothelioma. The trial demonstrated a statistically significant improvement in OS for patients treated with pembrolizumab with chemotherapy compared to those who received chemotherapy alone. Median OS was 17.3 months (95% CI: 14.4, 21.3) versus 16.1 months (95% CI: 13.1, 18.2) (hazard ratio [HR] 0.79 [95% CI: 0.64, 0.98]; p=0.0162).
Median PFS was 7.1 months (95% CI: 6.9, 8.1) vs 7.1 months (95% CI: 6.8, 7.7) in pembrolizumab plus chemotherapy and the chemotherapy alone arm, respectively (HR 0.80 [95% CI: 0.65, 0.99]; p=0.0194). Confirmed ORR was 52% (95% CI: 45.5, 59.0) in the pembrolizumab plus chemotherapy arm and 29% (95% CI: 23.0, 35.4) in the chemotherapy alone arm. Median DoR was 6.9 months (95% CI: 5.8, 8.3) and 6.8 months (95% CI: 5.5, 8.5), respectively.
Adverse reactions occurring in patients with MPM were similar to those receiving pembrolizumab with pemetrexed and platinum chemotherapy. See the prescribing information for complete details.
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression or unacceptable toxicity for up to 2 years.
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. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA) and Health Canada. The application reviews are ongoing at the other regulatory agencies.
Expedited Programs
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
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