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  6. 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
  1. Resources for Information | Approved Drugs

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

Podcast

Welcome back to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we’ll provide a quick update on two recent FDA cancer drug approvals.

On June 13, 2024, the FDA granted accelerated approval to repotrectinib (brand name Augtyro) for adult and pediatric patients 12 years and older with solid tumors that have a neurotrophic tyrosine receptor kinase gene fusion, 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, a multicenter, single-arm, open-label, multi-cohort trial in 88 adult patients with locally advanced or metastatic neurotrophic tyrosine receptor kinase gene fusion-positive solid tumors who had either received a prior tyrosine receptor kinase tyrosine kinase inhibitor or were tyrosine kinase inhibitor-naïve. All patients were assessed for central nervous lesions at baseline, and patients with symptomatic brain metastases were excluded. Tumor assessments were performed every 8 weeks.

The major efficacy outcome measures were overall response rate and duration of response according to RECIST v1.1 as assessed by blinded independent central review. Confirmed overall response rate in the tyrosine kinase inhibitor-naïve group was 58% and 50% in the tyrosine kinase inhibitor-pretreated group. Median duration of response was not estimable in the tyrosine kinase inhibitor-naïve group and 9.9 months in the tyrosine kinase inhibitor-pretreated group.

The most common adverse reactions reported in more than 20% of patients were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

On June 21, 2024, the FDA granted accelerated approval to adagrasib (brand name Krazati) plus cetuximab for adults with KRAS G12C-mutated locally advanced or metastatic colorectal cancer, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Efficacy was evaluated in KRYSTAL-1, a multicenter, single-arm expansion cohort trial. Eligible patients were required to have locally advanced or metastatic KRAS G12C-mutated colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, and a VEGF inhibitor, if eligible. Patients were treated with adagrasib 600 mg twice daily plus cetuximab administered either biweekly or weekly. Tumor assessments were performed every 6 weeks. Adagrasib discontinuation required cetuximab discontinuation, however patients could continue adagrasib if cetuximab was discontinued.

The major efficacy outcome measures were confirmed overall response rate and duration of response according to RECIST v1.1 assessed by blinded independent central review. In the 94 enrolled patients, overall response rate was 34%, all responses were partial responses, and median duration of response was 5.8 months. Thirty-one percent of responding patients had a duration of response of at least 6 months.

The most common adverse reactions reported in more than 20% of patients were rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, cough, dizziness, constipation, and peripheral neuropathy.

Full prescribing information for these approvals can be found on the web at www.fda.gov/drugsatfda.

Health care professionals should report serious adverse events to www.fda.gov/medwatch.

Follow the Division of Drug Information on X @FDA_Drug_Info and the Oncology Center of Excellence @FDAOncology. Send your feedback via email to FDAOncology@fda.hhs.gov. Thanks for tuning in to the D.I.S.C.O. Burst Edition.

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