FDA D.I.S.C.O. Burst Edition: FDA approvals of Augtyro (repotrectinib) for NTRK gene fusion-positive solid tumors and Krazati (adagrasib) for KRAS G12C-mutated colorectal cancer
Regulatory approval news: In an FDA D.I.S.C.O. Burst Edition update, the FDA granted accelerated approvals to repotrectinib (Augtyro) for NTRK gene fusion–positive solid tumors in adults and pediatric patients ≥12 years (June 13, 2024) and to adagrasib (Krazati) plus cetuximab for previously treated KRAS G12C–mutated locally advanced/metastatic colorectal cancer (June 21, 2024). Approvals were supported by single-arm trials (TRIDENT-1 and KRYSTAL-1) reporting overall response rate and duration of response.
FDA D.I.S.C.O. Burst Edition: two accelerated approvals (regulatory approval)
Augtyro (repotrectinib) — NTRK gene fusion–positive solid tumors
On June 13, 2024, the FDA granted accelerated approval to repotrectinib (Augtyro) for adult and pediatric patients ≥12 years with NTRK gene fusion–positive solid tumors that are locally advanced or metastatic, or where surgical resection is likely to result in severe morbidity, and that have progressed following treatment or have no satisfactory alternative therapy.
Efficacy was evaluated in TRIDENT-1 (multicenter, single-arm, open-label; 88 adults). Patients with symptomatic brain metastases were excluded. Primary outcomes were confirmed ORR and DOR (RECIST v1.1; blinded independent central review). ORR was 58% (TKI-naïve) and 50% (TKI-pretreated). Median DOR was not estimable (TKI-naïve) and 9.9 months (TKI-pretreated). Common adverse reactions (>20%) included dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, nausea.
Krazati (adagrasib) + cetuximab — KRAS G12C–mutated colorectal cancer
On June 21, 2024, the FDA granted accelerated approval to adagrasib (Krazati) plus cetuximab for adults with KRAS G12C–mutated locally advanced/metastatic colorectal cancer (per an FDA-approved test) after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
Efficacy was evaluated in KRYSTAL-1 (single-arm expansion; 94 patients): ORR 34% (all partial responses), median DOR 5.8 months; 31% of responders had DOR ≥6 months. Common adverse reactions (>20%) included rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, peripheral neuropathy.