Turning Point Therapeutics Presents Early Clinical Data for Repotrectinib From Care Study in Pediatric and Young Adult Patients at SIOP 2021 Virtual Congress
- Early Clinical Activity and Safety Profile Support Continued Investigation of Repotrectinib in Pediatric Tumors Harboring ALK, ROS1 or NTRK Alterations
- Repotrectinib Demonstrated Confirmed Responses in 3 of 4 TKI-Naïve Patients
“These early data for repotrectinib demonstrate encouraging clinical activity in this pediatric patient population,” said
Early Data from Phase 1/2 CARE Study
The primary objective of the Phase 1 dose escalation portion of the study is to evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of repotrectinib in pediatric patients less than 12 years old. The primary objective of the Phase 2 portion of the study is to determine the anti-tumor activity of repotrectinib in pediatric and young adult patients less than 25 years old. Repotrectinib is administrated in capsule or suspension formulation using weight-based dosing for patients less than 12 years old. Patients 12 to 25 years old can enroll directly into the Phase 2 portion of the study with a repotrectinib dose of 160 mg QD for the first 14 days and may increase to 160 mg BID thereafter.
The early Phase 1/2
The findings were reported in a pre-recorded presentation by
Preliminary Safety Analysis (n=10) and Pharmacokinetic Analysis
- Repotrectinib was generally well tolerated.
- The most frequently reported treatment-emergent adverse events (TEAEs) were anemia (n=5) and fatigue (n=5). Among patients with anemia, three had baseline history of anemia.
- Dizziness events (n=4) were grade 1 or 2 and none led to treatment discontinuation.
- No patients discontinued treatment due to reasons other than disease progression and no patients had TEAEs that led to dose reduction.
- No dose-limiting toxicities were reported.
- Preliminary pharmacokinetics data indicated that the exposure of repotrectinib in different age groups was comparable to the adult exposure at steady-state.
Preliminary Efficacy Analysis (n=8)
- Eight patients were evaluable for efficacy, including four TKI-naïve and four TKI-pretreated patients. TKI-naive patients included those with NTRK amplified anaplastic ependymoma (n=1), NTRK fusion glioblastoma multiforme (GBM)/high grade glioma (n=1), NTRK fusion sarcoma (n=1), and ROS1 fusion inflammatory myofibroblastic tumor (IMT) (n=1). TKI-pretreated patients included those with NTRK fusion GBM/high grade glioma (n=2), NTRK fusion mesoblastic nephroma (n=1), and NTRK fusion sarcoma (n=1).
- Three TKI-naïve patients (2 NTRK fusion solid tumors; 1 ROS1 fusion IMT) achieved confirmed responses. One of the three responding patients had a NTRK fusion GBM/high grade glioma, was previously treated with tumor resection, whole brain radiotherapy, and multi-agent chemotherapy, and achieved a complete response (CR) and remained in a response for 3.8+ months as of the data cutoff date. The other two confirmed responders remained in response with duration of response of 7.3+ and 12.1+ months, respectively.
- Of the four TKI-pretreated patients, one patient with NTRK fusion sarcoma had a best response of stable disease.
The Phase 1 dose finding portion of the study is ongoing in pediatric patients less than 12 years old to confirm the pediatric RP2D. The Phase 2 portion of the study is ongoing for patients 12 to 25 years old.
Turning Point also announced the publication of preclinical data of repotrectinib in neuroblastoma, the most common pediatric extracranial solid tumor, in the American Association of Cancer Research’s peer reviewed journal, Molecular Cancer Therapeutics. Preclinical studies described in the publication titled “Translational Strategies for Repotrectinib in Neuroblastoma” show that repotrectinib inhibits tumor growth and prolongs survival in patient-derived neuroblastoma xenograft models. In addition, the studies indicated that combining repotrectinib with chemotherapy may be a promising treatment paradigm for neuroblastoma patients.
About Turning Point Therapeutics Inc.
Turning Point Therapeutics is a clinical-stage precision oncology company with a pipeline of internally discovered investigational drugs designed to address key limitations of existing cancer therapies. The company’s lead drug candidate, repotrectinib, is a next-generation kinase inhibitor targeting the ROS1 and TRK oncogenic drivers of non-small cell lung cancer and advanced solid tumors. Repotrectinib, which is being studied in a registrational Phase 2 study in adults and a Phase 1/2 study in pediatric patients, has shown antitumor activity and durable responses among kinase inhibitor treatment-naïve and pre-treated patients. The company’s pipeline of drug candidates also includes elzovantinib, targeting MET, CSF1R and SRC, which is being studied in a Phase 1 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in MET; TPX-0046, targeting RET, which is being studied in a Phase 1/2 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in RET; and TPX-0131, a next-generation ALK inhibitor, which is being studied in a Phase 1/2 trial of previously treated patients with ALK-positive advanced or metastatic non-small cell lung cancer. The company is driven to develop therapies that mark a turning point for patients in their cancer treatment. For more information, visit www.tptherapeutics.com.
Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “plans”, “will”, “believes,” “anticipates,” “expects,” “intends,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements in this press release include statements regarding, among other things, the efficacy, safety and therapeutic potential of repotrectinib, and the results, conduct, progress and timing of Turning Point Therapeutics’ Phase 1/2
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Source: Turning Point Therapeutics, Inc.