FDA Approves Rozlytrek®, Third “Tumor-Agnostic” Drug

The U.S. Food and Drug Administration (FDA) approved Rozlytrek® (entrectinib) for adults and pediatric patients (12 years of age and older) with NTRK-positive solid tumors without a known acquired resistance mutation that are metastatic or where surgical resection is likely to result in severe morbidity and have progressed following treatment or have no satisfactory standard therapy. Entrectinib was also approved for adults with metastatic ROS1-positive non-small cell lung cancer (NSCLC).

This is the third approval for a “tumor-agnostic” drug, following the FDA approval of Vitrakvi® (larotrectinib)for the treatment of NTRK-positive solid tumors in 2018, and the approval of Keytruda® (pembrolizumab) for tumors with microsatellite instability-high or mismatch repair deficient tumors in 2017.

Improved response with entrectinib

Researchers investigated the efficacy of entrectinib in NTRK-positive tumors in 54 adults who received entrectinib at various doses and schedules in one of three multicenter, single-arm, clinical trials (ALKA, STARTRK-1, and STARTRK-2). Most patients (94%) received entrectinib 600 mg orally once daily. Researchers identified NTRK-positive tumors in local laboratories or a central laboratory using nucleic acid-based tests prior to enrollment.

The overall response rate (ORR) was 57% (95% CI, 43-71), and responses were observed across 10 different tumor types. The duration of response was six months or longer for 68% of patients and 12 months or longer for 45% of patients. The most common cancers in the study were sarcoma, NSCLC, mammary analogue secretory carcinoma, breast, thyroid, and colorectal.

Researchers investigated the efficacy of entrectinib in ROS1-positive metastatic NSCLC in 51 adults who received entrectinib at various doses and schedules in the same three clinical trials. Again, most patients (90%) received entrectinib 600 mg orally once daily. The ORR was 78% (95% CI, 65-89), and the duration of response was 12 months or longer for 55% of patients.

The most serious adverse events (AEs) associated with entrectinib were congestive heart failure, central nervous system effects, skeletal fractures, hepatotoxicity, hyperuricemia, QT interval prolongation, and vision disorders. The most common AEs are fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, increased weight, cough, vomiting, pyrexia, arthralgia, and vision disorders.