FDA D.I.S.C.O. Burst Edition: FDA approvals of Tecentriq (atezolizumab) for unresectable or metastatic alveolar soft part sarcoma, and Krazati (adagrasib) for KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer
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 December 9, 2022, the FDA approved atezolizumab (brand name Tecentriq), for adult and pediatric patients 2 years of age and older with unresectable or metastatic alveolar soft part sarcoma.
Efficacy was evaluated in Study ML39345, an open-label, single-arm study in 49 adult and pediatric patients with unresectable or metastatic alveolar soft part sarcoma. Eligible patients were required to have histologically or cytologically confirmed alveolar soft part sarcoma incurable by surgery and an ECOG performance status of 2 or less. Patients were excluded for primary central nervous system malignancy or symptomatic central nervous system metastases, clinically significant liver disease, or a history of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or active pneumonitis on imaging. Adult patients received 1200 mg intravenously and pediatric patients received 15 mg/kg, up to a maximum of 1200 mg, intravenously once every 21 days until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate and duration of response determined by an independent review committee using RECIST v1.1. Overall response rate was 24%. Of the 12 patients who experienced an objective response, 67% had a duration of response of 6 months or more, and 42% had a duration of response of 12 months or more.
The median patient age was 31 years, ranging between ages 12 to 70; 47 adult patients, of which 2% were 65 years of age or older, and 2 pediatric patients 12 years of age or older were enrolled; 51% were female, 55% White, 29% Black or African American, 10% Asian.
The most common adverse reactions occurring in 15% or more patients were musculoskeletal pain, fatigue, rash, cough, nausea, headache, hypertension, vomiting, constipation, dyspnea, dizziness, hemorrhage, insomnia, diarrhea, pyrexia, anxiety, abdominal pain, hypothyroidism, decreased appetite, arrhythmia, influenza-like illness, weight decreased, allergic rhinitis and weight increased.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 3 weeks ahead of the FDA goal date.
On December 12, 2022, the FDA granted accelerated approval to adagrasib (brand name Krazati), a RAS GTPase family inhibitor, for adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, as determined by an FDA-approved test, who have received at least one prior systemic therapy.
FDA also approved the QIAGEN therascreen KRAS RGQ PCR kit (tissue) and the Agilent Resolution ctDx FIRST Assay (plasma) as companion diagnostics for Krazati. If no mutation is detected in a plasma specimen, the tumor tissue should be tested.
Approval was based on KRYSTAL-1, a multicenter, single-arm, open-label clinical trial, which included patients with locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations. Efficacy was evaluated in 112 patients whose disease has progressed on or after platinum-based chemotherapy and an immune checkpoint inhibitor, given either concurrently or sequentially. Patients received adagrasib 600 mg orally twice daily until disease progression or unacceptable toxicity.
The main efficacy outcome measures were confirmed objective response rate according to RECIST 1.1, as evaluated by blinded independent central review, and duration of response. The objective response rate was 43% and median duration of response was 8.5 months.
The most common adverse reactions occurring in 20% or more patients were diarrhea, nausea, fatigue, vomiting, musculoskeletal pain, hepatotoxicity, renal impairment, dyspnea, edema, decreased appetite, cough, pneumonia, dizziness, constipation, abdominal pain, and QTc interval prolongation. The most common laboratory abnormalities, greater than 25%, were decreased lymphocytes, increased aspartate aminotransferase, decreased sodium, decreased hemoglobin, increased creatinine, decreased albumin, increased alanine aminotransferase, increased lipase, decreased platelets, decreased magnesium, and decreased potassium.
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 Program at MedWatch: The FDA Safety Information and Adverse Event Reporting Program.
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