ACTIVE_NOT_RECRUITING

Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-09-01

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04919811

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age ≥18 years (or ≥20 years as required by local regulations). 2. 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). 3. 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. 4. 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. 5. 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. 6. The patient can be either ROS1 TKI treatment naïve or treated with prior ROS1 TKI(s): * Cohort 3: Patients with locally advanced or metastatic ROS1-positive NSCLC. Prior treatment with ≥2 TKIs with ROS1 activity and disease progression. The patient can be either chemotherapy naïve or has received 1 line of systemic chemotherapy for locally advanced or metastatic ROS1-positive NSCLC, patients with known ROS1 resistant mutations are preferred. * Cohort 4: Patients with other ROS1-positive solid tumors, or NSCLC patients ineligible for Cohorts 1-3. Prior treatment with ≤3 TKIs with ROS1 activity. The patient can be either chemotherapy naïve or has received ≤2 lines of systemic chemotherapy for locally advanced or metastatic solid tumors. * Cohort 5: Patients with locally advanced or metastatic ROS1-positive NSCLC. The patient can be either chemotherapy naïve or has received ≤2 lines of systemic chemotherapy line of systemic chemotherapy for locally advanced or metastatic ROS1-positive NSCLC. ROS1-TKI-naïve or pretreated with TKI(s) having ROS1 activity. 7. At least 1 measurable disease per RECIST 1.1 as assessed by the investigator. 8. Eastern Cooperative Oncology Group Performance Status: 0 or 1. 9. Patient with a life expectancy ≥12 weeks based on the judgement of investigator. 10. Patients with adequate organ function meeting the following criteria: 1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤3.0 × upper limit of normal (ULN) (or ≤5.0 × ULN, for patients with concurrent liver metastases) 2. Serum total bilirubin: ≤1.5 × ULN (≤3.0 × ULN for patients with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy) 3. Absolute neutrophil count: ≥1,500/μL 4. Platelet count: ≥100,000/μL 5. Hemoglobin: ≥9.0 g/dL 6. Serum creatinine ≤1.5 × ULN and estimated creatinine clearance (CLcr) ≥45 mL/min as calculated using the method standard for the institution (e.g., Cockcroft - Gault Equation) 11. Males and/or females who meet any of the following criteria: 12. For all females of childbearing potential, a negative pregnancy test must be obtained within 7 days before starting study treatment. Female patients of non childbearing potential must meet at least 1 of the following criteria: 13. The patient is willing and capable to give written informed consent. 14. The patient is willing and capable to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures. 15. The patient is willing and capable to comply with study site's COVID-19 policies. 1. 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. 2. Major surgical procedure, open biopsy, or significant traumatic injury ≤4 weeks before the first dose of taletrectinib. 3. Radiation outside the chest and brain \<7 days prior to C1D1. 4. 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. 5. 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. 6. Patients with untreated spinal cord compression caused by tumor and/or cancerous meningitis. 7. History or evidence of interstitial fibrosis, interstitial lung disease or drug-induced pneumonitis (Excluding clinically insignificant or asymptomatic post radiation pneumonitis). 8. Any gastrointestinal disorders that may affect absorption of oral medications. * With past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBcAb\] and absence of hepatitis B surface antigen \[HBsAg\]); or * With inactive HBV carrier state (defined as HBsAg positive, with normal ALT, and HBV DNA \<2,000 IU/mL or \<10,000 copies/mL).	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

1. Age ≥18 years (or ≥20 years as required by local regulations).
2. 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).
3. 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.
4. 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.
5. 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.
6. The patient can be either ROS1 TKI treatment naïve or treated with prior ROS1 TKI(s):
* Cohort 3: Patients with locally advanced or metastatic ROS1-positive NSCLC. Prior treatment with ≥2 TKIs with ROS1 activity and disease progression. The patient can be either chemotherapy naïve or has received 1 line of systemic chemotherapy for locally advanced or metastatic ROS1-positive NSCLC, patients with known ROS1 resistant mutations are preferred.
* Cohort 4: Patients with other ROS1-positive solid tumors, or NSCLC patients ineligible for Cohorts 1-3. Prior treatment with ≤3 TKIs with ROS1 activity. The patient can be either chemotherapy naïve or has received ≤2 lines of systemic chemotherapy for locally advanced or metastatic solid tumors.
* Cohort 5: Patients with locally advanced or metastatic ROS1-positive NSCLC. The patient can be either chemotherapy naïve or has received ≤2 lines of systemic chemotherapy line of systemic chemotherapy for locally advanced or metastatic ROS1-positive NSCLC. ROS1-TKI-naïve or pretreated with TKI(s) having ROS1 activity.
7. At least 1 measurable disease per RECIST 1.1 as assessed by the investigator.
8. Eastern Cooperative Oncology Group Performance Status: 0 or 1.
9. Patient with a life expectancy ≥12 weeks based on the judgement of investigator.
10. Patients with adequate organ function meeting the following criteria:
1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤3.0 × upper limit of normal (ULN) (or ≤5.0 × ULN, for patients with concurrent liver metastases)
2. Serum total bilirubin: ≤1.5 × ULN (≤3.0 × ULN for patients with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy)
3. Absolute neutrophil count: ≥1,500/μL
4. Platelet count: ≥100,000/μL
5. Hemoglobin: ≥9.0 g/dL
6. Serum creatinine ≤1.5 × ULN and estimated creatinine clearance (CLcr) ≥45 mL/min as calculated using the method standard for the institution (e.g., Cockcroft - Gault Equation)
11. Males and/or females who meet any of the following criteria:
12. For all females of childbearing potential, a negative pregnancy test must be obtained within 7 days before starting study treatment. Female patients of non childbearing potential must meet at least 1 of the following criteria:
13. The patient is willing and capable to give written informed consent.
14. The patient is willing and capable to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
15. The patient is willing and capable to comply with study site's COVID-19 policies.
1. 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.
2. Major surgical procedure, open biopsy, or significant traumatic injury ≤4 weeks before the first dose of taletrectinib.
3. Radiation outside the chest and brain \<7 days prior to C1D1.
4. 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.
5. 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.
6. Patients with untreated spinal cord compression caused by tumor and/or cancerous meningitis.
7. History or evidence of interstitial fibrosis, interstitial lung disease or drug-induced pneumonitis (Excluding clinically insignificant or asymptomatic post radiation pneumonitis).
8. Any gastrointestinal disorders that may affect absorption of oral medications.
* With past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBcAb\] and absence of hepatitis B surface antigen \[HBsAg\]); or
* With inactive HBV carrier state (defined as HBsAg positive, with normal ALT, and HBV DNA \<2,000 IU/mL or \<10,000 copies/mL).

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Principal Investigator

Wei Wang, MD, PhD

STUDY_DIRECTOR

Nuvation Bio Inc.

Study Locations (Sites)

Beverly Hills Cancer Center

Beverly Hills, California, 90211

United States

The Oncology Institute of Hope and Innovation

Glendale, California, 91204

United States

Moores Cancer Center at UC San Diego

La Jolla, California, 92037

United States

Keck Medicine of University of Southern California

Los Angeles, California, 90089

United States

UCI Medical Center

Orange, California, 92868

United States

Ventura County Hematology-Oncology Specialists

Oxnard, California, 93030

United States

SCRI - Florida Cancer Specialists South

Fort Myers, Florida, 33901

United States

Memorial Cancer Institute at Memorial Hospital East

Hollywood, Florida, 33021

United States

Cancer Specialists of North Florida

Jacksonville, Florida, 92868

United States

Memorial Cancer Institute at Memorial Hospital West

Pembroke Pines, Florida, 33028

United States

SCRI - Hematology Oncology Clinic

Baton Rouge, Louisiana, 70809

United States

Mayo Clinic

Rochester, Minnesota, 55902

United States

Center for Cancer Research

Brick, New Jersey, 08724

United States

Cleveland Clinic Foundation

Cleveland, Ohio, 44195

United States

SCRI - Tennessee Oncology

Nashville, Tennessee, 37203

United States

Texas Oncology, P.A.

Dallas, Texas, 75246

United States

Renovatio Clinical

El Paso, Texas, 19915

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Renovatio Clinical

The Woodlands, Texas, 77380

United States

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405

United States

Collaborators and Investigators

Sponsor: Nuvation Bio Inc.

Wei Wang, MD, PhD, STUDY_DIRECTOR, Nuvation Bio Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-09-01

Study Completion Date2027-12

Study Record Updates

Study Start Date2021-09-01

Study Completion Date2027-12

Terms related to this study

Additional Relevant MeSH Terms

Non Small Cell Lung Cancer