FDA Approves Entrectinib for NTRK Solid Tumors and ROS-1 NSCLC

August 16, 2019

On August 15, 2019, the Food and Drug Administration granted accelerated approval to entrectinib (ROZLYTREK, Genentech Inc.) for adults and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory standard therapy.

Today, FDA also approved entrectinib for adults with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive.

Efficacy in NTRK-positive tumors was investigated in 54 adult patients who received entrectinib at various doses and schedules in one of three multicenter, single-arm, clinical trials: ALKA, STARTRK-1 (NCT02097810) and STARTRK-2 (NCT02568267); 94% received entrectinib 600 mg orally once daily. Identification of positive NTRK gene fusion status was determined in local laboratories or a central laboratory using nucleic acid-based tests prior to enrollment.

Among 54 adult patients, the overall response rate as determined by independent review was 57% (95% CI: 43, 71). Response duration was 6 months or longer for 68% of patients and 12 months or longer for 45% of patients. The most common cancers were sarcoma, NSCLC, mammary analogue secretory carcinoma, breast, thyroid, and colorectal.

Efficacy in ROS1-positive metastatic NSCLC was investigated in 51 adult patients who received entrectinib at various doses and schedules in the same three trials; 90% received entrectinib 600 mg orally once daily. The overall response rate was 78% (95% CI: 65, 89) and response duration was 12 months or longer for 55% of patients. 

The most serious adverse reactions to entrectinib are congestive heart failure, central nervous system effects, skeletal fractures, hepatotoxicity, hyperuricemia, QT interval prolongation, and vision disorders. The most common adverse reactions in at least 20% of patients were fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, increased weight, cough, vomiting, pyrexia, arthralgia, and vision disorders.

The recommended entrectinib dose for adults with NTRK gene fusion-positive solid tumors or with ROS1-positive NSCLC is 600 mg orally once daily. For pediatric patients ≥ 12 years with NTRK gene fusion-positive solid tumors, the prescribing information provides dosage recommendations based on body surface area.

View full prescribing information for ROZLYTREK.

Continued approval for the NTRK-positive tumors may be contingent upon verification and description of clinical benefit in the confirmatory trials. Entrectinib received priority review, Breakthrough Therapy, and Orphan Drug Designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Health care 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.

Check out recent approvals at the OCE’s podcast, Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.).

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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