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Augtyro (repotrectinib) - 2 indications
Scroll down for more information on each indication:
- for the treatment of ROS1-positive non-small cell lung cancer; approved November of 2023
- for the treatment of NTRK-positive locally advanced or metastatic solid tumors; approved June of 2024
General Information
Augtyro (repotrectinib) is a kinase inhibitor.
Augtryo is specifically indicated:
- for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC);
- for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy
- This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials
Dosing/Administration
- Augtryo is supplied as capsules for oral administration.
- Select patients for based on the presence of ROS1 rearrangement(s) in tumor specimens (NSCLC) or based on the presence of NTRK1/2/3 rearrangements (solid tumors) in tumor specimens.
- Prior to initiating Augtry, discontinue strong and moderate CYP3A inhibitors for 3 to 5 elimination half-lives of the CYP3A inhibitor
- Prior to initiation of Augtryo evaluate liver function tests including bilirubin and uric acid level
- The recommended dosage of Augtryo is 160 mg taken orally once daily with or without food for 14 days, then increase to 160 mg twice daily and continue until disease progression or unacceptable toxicity.
Mechanism of Action
Repotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC. Fusion proteins that include ROS1 or TRK domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Repotrectinib exhibited anti-tumor activity in cultured cells expressing ROS1 fusions and mutations. Repotrectinib also inhibited cell proliferation in cultured cells expressing NTRK fusions and mutations.
Side Effects
Adverse effects associated with the use of Augtryo may include, but are not limited to, the following:
- dizziness
- dysgeusia
- peripheral neuropathy
- constipation
- dyspnea
- ataxia
- fatigue
- cognitive disorders
- muscular weakness
Indication 1 - ROS1-positive non-small cell lung cancer
approved November of 2023
Clinical Trial Results
The FDA approval of Augtryo was based on the TRIDENT-1 study, an open-label, single-arm, Phase 1/2 trial that evaluated Augtryo in TKI-naïve and TKI-pretreated patients. In TKI-naïve patients (n=71), the primary endpoint of objective response rate (ORR), defined as the percentage of people treated within a certain period of time whose tumor size decreased (partial response) or who no longer have signs of cancer (complete response), was 79%. The median duration of response (mDOR) was 34.1 months. Among patients pretreated with one prior ROS1 TKI and no prior chemotherapy (n=56), the ORR was 38% and the mDOR was 14.8 months. Among those who had measurable central nervous system (CNS) metastases at baseline, responses in intracranial lesions were observed in 7 of 8 TKI-naïve patients (n=71) and 5 of 12 of those who were TKI-pretreated (n=56).
Indication 2 - for the treatment of NTRK-positive locally advanced or metastatic solid tumors
approved June of 2024
Clinical Trial Results
The approval is based on results from the Phase 1/2 TRIDENT-1 study, which evaluated Augtyro in adult patients with NTRK-positive solid tumors. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The TRIDENT-1 trial included both TKI-naïve (n=40) and TKI-pretreated (n=48) patients with NTRK-positive locally advanced/metastatic solid tumors collectively representing 15 different types of cancer. In TKI-naïve patients, with a median follow up of 17.8 months, 58% had a confirmed objective response rate (cORR); of those, 43% experienced partial responses (PR) and 15% had complete responses (CR). Of the TKI-naïve responding patients, 83% were still in response at one year with Augtyro. The median duration of response (mDOR) was not yet reached. In TKI-pretreated patients, with a median follow up of 20.1 months, the cORR was 50%; of those, 50% experienced PR and no patients achieved CR. Additionally, 42% of TKI-pretreated responding patients were still in response at one year with Augtyro. The mDOR was 9.9 months.1 Among those who had measurable central nervous system (CNS) metastases at baseline, intracranial response was observed in 2 out of 2 TKI-naïve patients and in 3 out of 3 TKI-pretreated patients.
Approval Date: 2023-11-01
Company Name: Bristol Myers Squibb