The U.S. Food and Drug Administration (FDA) announced on August 9 that it has fully approved Gavreto (pralsetinib) for the treatment of adult patients with non-small cell lung cancer (NSCLC) who have tested positive for metastatic rearrangement (RET) fusions during transfection in trials approved by the FDA.
Gavreto is a once-daily oral RET-targeted therapy that selectively and potently inhibits RET alterations (fusions and mutations, including predicted resistance mutations) that cause various cancers, including approximately 1–2% of NSCLC patients. Pralsetinib previously received accelerated approval from the FDA on September 4, 2020, for the same indication.
Efficacy is based on data from the Phase 1/2 open-label ARROW trial (ClinicalTrials.gov identifier: NCT03037385). This multi-cohort study included patients with metastatic RET fusion-positive non-small cell lung cancer who had progressed on platinum-based chemotherapy, as well as treatment-naïve patients with metastatic non-small cell lung cancer.
Study participants received oral Gavreto 400 mg once daily until disease progression or unacceptable toxicity. The primary outcome measures were overall response rate (ORR) and duration of response (DOR).
In 130 patients who had previously received platinum-based chemotherapy, the overall response rate (ORR) was 63% (95% CI, 54–71); 6% of patients achieved a complete response, and 57% achieved a partial response. The median risk was 38.8 months (95% confidence interval 14.8, not estimable); 66% of patients had a response lasting at least 12 months. In this study population, 54 patients had received prior anti-PD-1 or anti-PD-1I therapy, or concurrently platinum-based chemotherapy. The ORR in this subgroup was 59% (95% CI, 45–72), and the median DOR was 22.3 months (95% CI, 8.0, not estimable).
In 107 treatment-naïve patients, the ORR was 78% (95% CI, 68–85); 7% of patients achieved a complete response, and 71% achieved a partial response. The median hazard ratio was 13.4 months (95% CI, 9.4–23.1); 45% of patients had a response lasting at least 12 months.
Regarding safety, the most common adverse reactions observed with Gavreto included musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, fever, and cough.
