A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of Taletrectinib in Patients With Advanced or Metastatic ROS1 Positive NSCLC and Other Solid Tumors

Nuvation Bio Inc.142 sites in 6 countries217 target enrollmentSeptember 1, 2021

ConditionsNon Small Cell Lung Cancer

InterventionsTaletrectinib

DrugsTaletrectinib

Overview

Phase: Phase 2
Intervention: Taletrectinib
Conditions: Non Small Cell Lung Cancer
Sponsor: Nuvation Bio Inc.
Enrollment: 217
Locations: 142
Primary Endpoint: Objective response rate (ORR) by independent radiology review committee (IRC)
Status: Active, not recruiting
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

The main purpose of the study is to evaluate safety and efficacy of taletrectinib (also known as AB-106 or DS-6051b) monotherapy in the treatment of advanced NSCLC.

Detailed Description

This is a global Phase 2, multicenter, single-arm, open label study of taletrectinib in patients of NSCLC harboring with ROS1 fusion gene. About 214 patients will be enrolled and divided into 5 cohorts, depending on past history of ROS1 TKI treatment. Taletrectinib is administered once daily in 21-day cycles. Patients will continue with the treatment on taletrectinib until progression of disease as determined by the investigator. The tumor response evaluation will be conducted on a regular basis until progression of disease. Long-term survival follow-up will also be conducted.

Registry

clinicaltrials.gov

Start Date

September 1, 2021

End Date

December 1, 2027

Last Updated

3 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Nuvation Bio Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥18 years (or ≥20 years as required by local regulations).
•Histologically or cytologically confirmed diagnosis of locally advanced (including inoperable Stage IIIA or IIIB NSCLC) or metastatic NSCLC (Cohorts 1-3, 5) or other solid tumors including NSCLC patients ineligible for other cohorts (Cohort 4).
•Evidence of ROS1 fusion by a validated assay as performed in Clinical Laboratory Improvement Amendments (CLIA)-certified or locally equivalent diagnostic laboratories. The molecular assays (i.e., Reverse Transcription Polymerase Chain Reaction \[RT-PCR\], Next-generation Sequencing \[NGS\]) are highly recommended.
•Sufficient tumor tissue is required for patients in Cohort 1 and for TKI-naïve patients in Cohort 5 in order to perform confirmatory ROS1 fusion testing at the designated central laboratories. For patients in Cohort 1 and for TKI-naïve patients in Cohort 5, an archival tumor tissue specimen should be available and collected prior to enrollment. If archival tumor tissue is unavailable, then a fresh biopsy must be performed. Tumor tissue for patients in other cohorts is highly recommended, and tumor tissue obtained after progression on the most recent prior ROS1 TKI therapy in these cohorts is preferred. Cytology samples (e.g., pleural effusion cell pellets) may be acceptable for patients in Cohorts 2-4, and patients in Cohort 5 that received prior treatment with TKI(s) having ROS1 activity.
•Patients with central nervous system (CNS) involvement, including leptomeningeal carcinomatosis, must be stable (either asymptomatic or previously treated and controlled are allowed:
•Seizure prophylaxis is permitted with non-enzyme inducing anti-epileptic drugs (non-EIAEDs).
•Corticosteroid treatment at a stable or decreasing dose within 7 days prior to the first dose of taletrectinib.
•Whole brain radiation therapy (WBRT) must be completed at least 14 days and stereotactic radiotherapy, stereotactic radiosurgery, or gamma knife radiotherapy at least 7 days prior to enrollment; the patient must be clinically stable for 7 days according to investigator judgement prior to first dose of taletrectinib.
•The patient can be either ROS1 TKI treatment naïve or treated with prior ROS1 TKI(s):
•o Cohort 1: Patients with locally advanced or metastatic ROS1-positive NSCLC. Systemic chemotherapy naïve or pretreated with 1 prior line of chemotherapy but never treated with any ROS1 TKI.

Exclusion Criteria

•Treatment with small molecule anticancer therapy including other investigational agents or cytotoxic systemic anticancer therapy within 2 weeks (or 5 half-lives of the compound, whichever is shorter) prior to the first dose of taletrectinib; or treatment with monoclonal antibodies, including immune checkpoint inhibitors within 4 weeks before the first dose of taletrectinib.
•Major surgical procedure, open biopsy, or significant traumatic injury ≤4 weeks before the first dose of taletrectinib.
•Note: Placement of vascular access device is not considered major surgery. Other minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.
•Radiation outside the chest and brain \<7 days prior to C1D
•Have been diagnosed with another primary malignancy other than NSCLC except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
•Adverse events due to prior therapy are unresolved to ≤ CTCAE Grade 1 or has not returned to baseline, by the first dose of taletrectinib except for AEs not constituting a safety risk to the patient based on the judgment of investigators.
•Patients with untreated spinal cord compression caused by tumor and/or cancerous meningitis.
•History or evidence of interstitial fibrosis, interstitial lung disease or drug-induced pneumonitis (Excluding clinically insignificant or asymptomatic post radiation pneumonitis).
•Any gastrointestinal disorders that may affect absorption of oral medications.
•Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV), hepatitis C virus (HCV), or severe acute respiratory syndrome coronavirus 2 (SARS CoV 2), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness. Note that the following are permitted: