Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC

NCT04919811 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: AB-106-G208
• Study Type: interventional
• Target: 217
• Locations: 9 countries
• Sites: 77

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.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) by independent radiology review committee (IRC)

  Confirmed ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by an independent radiology review committee (IRC)

  Up to 4 years

Secondary Outcomes (4)

• Progression-free survival (PFS)

  Up to 4 years

• Objective response rate (ORR) assessed by investigators

  Up to 4 years

• Safety and tolerability of taletrectinib

  Up to 4 years

• Pharmacokinetic (PK) profile of taletrectinib

  Up to 4 years

Other Outcomes (2)

• Intracranial progression-free survival (IC-PFS)

  Up to 4 years

• Intracranial objective response rate (IC-ORR)

  Up to 4 years

Study Arms (1)

Taletrectinib

EXPERIMENTAL

Single-arm trial whereby all consented, enrolled, eligible patients receive taletrectinib

Drug: Taletrectinib

Interventions

Taletrectinib DRUG

400mg or 600mg QD

Also known as: DS-6051b, AB-106

Taletrectinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• o Cohort 2: Patients with locally advanced or metastatic ROS1-positive NSCLC. Prior treatment with 1 approved ROS1 TKI (crizotinib or entrectinib) 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.
• 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.
• At least 1 measurable disease per RECIST 1.1 as assessed by the investigator.

You may not qualify if:

• 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 C1D1.
• 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.
• \. 9. 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:
• ○ Patients treated for hepatitis C (HCV) or HIV with no detectable viral load; for at least 1 month prior to the first dose of taletrectinib.
• Note: caution with drug drug interactions of concomitant anti HIV agents and CYP3A substrates.
• ○ Patients with known hepatitis B (HBV) infections:
• 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).

Sponsors & Collaborators

• Nuvation Bio Inc.: lead

Study Sites (77)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

The Oncology Institute of Hope and Innovation

Glendale, California, 91204, United States

Location

Moores Cancer Center at UC San Diego

La Jolla, California, 92037, United States

Location

Keck Medicine of University of Southern California

Los Angeles, California, 90089, United States

Location

UCI Medical Center

Orange, California, 92868, United States

Location

Ventura County Hematology-Oncology Specialists

Oxnard, California, 93030, United States

Location

SCRI - Florida Cancer Specialists South

Fort Meyers, Florida, 33901, United States

Location

Memorial Cancer Institute at Memorial Hospital East

Hollywood, Florida, 33021, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 92868, United States

Location

Memorial Cancer Institute at Memorial Hospital West

Pembroke Pines, Florida, 33028, United States

Location

SCRI - Hematology Oncology Clinic

Baton Rouge, Louisiana, 70809, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Center for Cancer Research

Brick, New Jersey, 08724, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

SCRI - Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology, P.A.

Dallas, Texas, 75246, United States

Location

Renovatio Clinical

El Paso, Texas, 19915, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Renovatio Clinical

The Woodlands, Texas, 77380, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Location

McGill University Health Centre Research Institute

Montreal, Quebec, Canada

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Hunan Cancer Hospital

Changsha, China

Location

West China Hospital

Chengdu, China

Location

Shandong Cancer Hospital

Jinan, China

Location

Wuhan Union Hospital

Wuhan, China

Location

Henan Cancer Hospital

Zhengzhou, China

Location

CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel

Bron, France

Location

CHU Grenoble Alpes- Hospital Michallon

La Tronche, 38700, France

Location

Centre Léon Bérard

Lyon 08, 69373, France

Location

Centre d'Essais Précoces de Cancerologie de Marseille

Marseille, 13005, France

Location

APHP- Hôpital Europeen Georges Pompidou (HEGP)

Paris, 75015, France

Location

CHU de Poitiers Pole regional

Poitiers, 86000, France

Location

Institut Jean Godinot

Reims, 51726, France

Location

CHU Rennes - Hospital Pontchaillou

Rennes, 35033, France

Location

Institut De Cancérologie De L'ouest

Saint-Herblain, 44805, France

Location

Institut Gustave Roussy

Saint-Herblain, 44805, France

Location

Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico

Bari, 70124, Italy

Location

Humanitas Istituto Clinico Catanese, Misterbinanoco

Catania, 95045, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

IEO Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

AOU Cagliari- P.O. Policlinico Universitario Duilio Casula

Monserrato, 09042, Italy

Location

Azienda Ospedaliera Universitaria- Università degli Studi della Campania

Naples, 80131, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

National Cancer Center Hospital East

Kashiwa, 104-0045, Japan

Location

Sendai Kousei Hospital

Miyagi, 980-0873, Japan

Location

Aichi Cancer Center Hospital

Nagoya, 464-8681, Japan

Location

Kindai University Hospital

Osaka, 589-8511, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Instytut Centrum Zdrowia Matki Polki

Lodz, Poland

Location

Med-Polonia Sp. z o.o.

Poznan, 60-693, Poland

Location

MICS Centrum Medyczne Toruńa

Torun, 87-100, Poland

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Pusan National University Yangsan Hospital

Gyeongsang, 999007, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun, 58128, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Clinica Mi Tres Torres

Barcelona, 08017, Spain

Location

Hospital Quironsalud Barcelona

Barcelona, 08023, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

ICO l'Hospitalet - Hospital Duran i Reynals L'Hospitalet de Llobregat

Barcelona, 08908, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Instituto Valenciano de Oncologia IVO

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Related Publications (2)

• Perol M, Li W, Pennell NA, Liu G, Ohe Y, De Braud F, Nagasaka M, Felip E, Xiong A, Zhang Y, Fan H, Wang X, Li S, Lai RK, Ran F, Zhang X, Chen W, Bazhenova L, Zhou C. Taletrectinib in ROS1+ Non-Small Cell Lung Cancer: TRUST. J Clin Oncol. 2025 Jun;43(16):1920-1929. doi: 10.1200/JCO-25-00275. Epub 2025 Apr 3.

  PMID: 40179330 DERIVED

• Nagasaka M, Ohe Y, Zhou C, Choi CM, Yang N, Liu G, Felip E, Perol M, Besse B, Nieva J, Raez L, Pennell NA, Dimou A, Marinis F, Ciardiello F, Seto T, Hu Z, Pan M, Wang W, Li S, Ou SI. TRUST-II: a global phase II study of taletrectinib in ROS1-positive non-small-cell lung cancer and other solid tumors. Future Oncol. 2023 Jan;19(2):123-135. doi: 10.2217/fon-2022-1059. Epub 2023 Mar 6.

  PMID: 36877099 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

taletrectinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Wei Wang, MD, PhD

  Nuvation Bio Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: June 9, 2021
• Study Start: September 1, 2021
• Primary Completion: June 11, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 7, 2026

Record last verified: 2025-10

Locations

CN (8); FR (10); US (20); CA (2); ES (12); IT (9); JP (8); PL (3); KR (5)