FDA Approves Atezolizumab for BRAF V600 Unresectable or Metastatic Melanoma
On July 30, 2020, the U.S. Food and Drug Administration (FDA) approved atezolizumab (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-braf-v600-unresectable-or-metastatic-melanoma?utm_campaign=Oncology%207-31-2020%20atezolizumab&utm_medium=email&utm_source=Eloqua&elqTrackId=38552F7B5C55F017B66C6336EE62E571&elq=ed2a1a77153c4206b2c475552704cfc9&elqaid=13603&elqat=1&elqCampaignId=11643) (Tecentriq®) in combination with cobimetinib and vemurafenib for patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.
Efficacy in combination with cobimetinib and vemurafenib was evaluated in a double-blind, randomized (1:1), placebo-controlled, multicenter trial (IMspire150; NCT02908672) in 514 patients. After a 28-day cycle of cobimetinib and vemurafenib, patients received atezolizumab 840 mg via IV infusion every two weeks in combination with cobimetinib 60 mg orally once daily (21 days on, 7 days off) and vemurafenib 720 mg orally twice daily, or placebo in combination with cobimetinib 60 mg orally once daily (21 days on, 7 days off) and vemurafenib 960 mg orally twice daily.
The primary efficacy outcome measure was investigator-assessed progression-free survival (PFS) per response evaluation criteria in solid tumors 1.1. Median PFS was 15.1 months (95% CI = 11.4, 18.4) in the atezolizumab arm and 10.6 months (95% CI = 9.3, 12.7) in the placebo arm (HR = 0.78; 95% CI = 0.63, 0.97; p = 0.0249).
The most common adverse reactions (≥ 20%) were rash, musculoskeletal pain, nausea, fatigue, hepatotoxicity, pyrexia, nausea, pruritus, edema, stomatitis, hypothyroidism, and photosensitivity reaction.
The recommended atezolizumab dose, following completion of a 28-day cycle of cobimetinib and vemurafenib, is 840 mg every two weeks with cobimetinib 60 mg orally once daily (21 days on, 7 days off) and vemurafenib 720 mg orally twice daily.
The review used Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application six weeks ahead of its goal date.
FDA collaborated with Switzerland’s Swissmedic to review the application as part of Project Orbis. (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis)
FDA granted the application priority review and atezolizumab was granted orphan product designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-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 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).