PRINCETON -
Administered as an oral therapy, Augtyro is a tyrosine kinase inhibitor (TKI) targeting ROS1 oncogenic fusions.
The approval is based on the TRIDENT-1 study, an open-label, single-arm, Phase 1/2 trial that evaluated Augtyro in TKI-naive and TKI-pretreated patients.2 In TKI-naive 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% (95% Confidence Interval [CI]: 68 to 88).1,3 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% (95% CI: 25 to 52) and the mDOR was 14.8 months.1 Among those who had measurable central nervous system (CNS) metastases at baseline, responses in intracranial lesions were observed in 7 of 8 TKI-naive patients (n=71) and 5 of 12 of those who were TKI-pretreated (n=56).
'New treatment options continue to be needed for patients with ROS1 fusion-positive NSCLC that support important clinical goals, including achieving durable therapeutic responses,' said
Augtyro is associated with the following Warnings & Precautions: central nervous system (CNS) effects, interstitial lung disease (ILD)/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, skeletal fractures, and embryo-fetal toxicity.
'While progress has been made in the treatment of NSCLC over the past decade, there is still a need to address this particularly difficult-to-treat form of the disease with innovative science and a targeted approach,' said
'ROS1-positive NSCLC patients and their families face a stressful journey because our cancer can be difficult to treat, especially when it spreads to the brain,' said
Augtyro is designed to minimize interactions that can lead to certain forms of treatment resistance in ROS1-positive metastatic NSCLC patients. It is expected to be available to patients in the
About TRIDENT-1
TRIDENT-1 is a global, multicenter, single-arm, open-label, multi-cohort Phase 1/2 clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of repotrectinib in patients with advanced solid tumors, including non-small cell lung cancer (NSCLC).1,2 Phase 1/2 includes patients with locally advanced or metastatic solid tumors harboring ROS1 fusions.2 Additional analyses of the trial are still being conducted; asymptomatic central nervous system (CNS) metastases are allowed.1,2 The trial excludes patients with symptomatic brain metastases, among other exclusion criteria.1 Phase 1 of the trial included the dose escalation that determined the recommended Phase 2 dose.
Phase 2 of the trial has a primary endpoint of overall response rate (ORR).1,2 Key secondary endpoints include duration of response (DOR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by Blinded Independent Central Review (BICR), progression-free survival (PFS), and intracranial response in six distinct expansion cohorts, including tyrosine kinase inhibitor (TKI)-naive and TKI-pretreated patients with ROS1-positive locally advanced or metastatic NSCLC.
In TRIDENT-1, of the 79% (95% Confidence Interval [CI]: 68 to 88) of TKI-naive patients who responded to treatment, 6% experienced complete responses and 73% experienced partial responses.1 The median duration of response (mDOR) was 34.1 months.1 Of the 38% (95% CI: 25 to 52) of TKI-pretreated patients (n=56) who responded to treatment, 5% experienced complete responses and 32% experienced partial responses and the mDOR was 14.8 months.1 Among those who had measurable CNS metastases at baseline as assessed by BICR, responses in intracranial lesions were observed in 7 of 8 TKI-naive patients (n=71) and in 5 of 12 of those who were TKI-pretreated (n=56).
The FDA-approved dosing for Augtyrois 160 mg orally once daily for 14 days, then increased to 160 mg twice daily until disease progression or unacceptable toxicity.
Select Safety Profile From TRIDENT-1
Permanent discontinuation of Augtyro occurred in 8% of patients.1 Augtyro dosage was interrupted due to an adverse reaction in 48% of patients, and dose reductions due to an adverse event occurred in 35% of patients.1 Serious adverse reactions occurred in 33% of patients who received Augtyro.1 Serious adverse reactions in 2% of patients included pneumonia (5.7%), dyspnea (3.8%), pleural effusion (3.4%) and hypoxia (3%).1 Fatal adverse reactions occurred in 4.2% of patients who received Augtyro, including death, pneumonia, pneumonia aspiration, cardiac arrest, sudden cardiac death, cardiac failure, sudden death, hypoxia, dyspnea, respiratory failure, tremor, and disseminated intravascular coagulation.1 The most common (20%) adverse reactions were dizziness (63%), dysgeusia (48%), peripheral neuropathy (47%), constipation (36%), dyspnea (30%), ataxia (28%), fatigue (24%), cognitive disorders (23%), and muscular weakness (21%).1 Grade 3 dizziness occurred in 1.9% of patients.1 The most common and serious adverse reactions and fatal events were evaluated in 264 patients who received the Phase 2 recommended dose of Augtyro in TRIDENT-1.1
About
Lung cancer is the leading cause of cancer deaths in the United States.12 The two main types of lung cancer are non-small cell and small cell.12 Non-small cell lung cancer (NSCLC) represents up to 85% of diagnoses.12 Survival rates vary depending on the stage and type of the cancer when diagnosed.13 ROS1 fusions are rare and occur in about 1-2% of patients with NSCLC.10 With a median age of 50, patients with tumors that are ROS1-positive tend to be younger than the average lung cancer patient, more often female than male and may have little to no smoking history.10ROS1-positive lung cancer tends to be aggressive and can often spread to the brain.10ROS1 tyrosine kinase inhibitor (TKI) therapy is the current standard of care for patients with a tumor harboring this gene alteration.4
Cancer can have a relentless grasp on many parts of a patient's life, and
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Cautionary Statement Regarding Forward-Looking Statements
This press release contains 'forward-looking statements' within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, whether Augtyro (repotrectinib) for the indication described in this release will be commercially successful, that any marketing approvals, if granted, may have significant limitations on their use, and that continued approval of Augtyro (repotrectinib) for such indication described in this release may be contingent upon verification and description of clinical benefit in confirmatory trials. No forward-looking statement can be guaranteed.
Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect
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