Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC (TRUST-II)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Taletrectinib

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 224 patients will be enrolled and divided into 6 cohorts, depending on past history of ROS1 TKI treatment.

In the cohorts open to enrollment, taletrectinib will be administered either 400mg or 600mg once daily in 21-day cycles. In one cohort, this will be in combination with carboplatin and pemetrexed both administered by IV infusion in 21-day cycles for 4 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 be conducted as well.

• Study Type: Interventional
• Enrollment (Estimated): 224
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lian Li; Phone Number: +1 212-466-6378; Email: trials@anhearttherapeutics.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Recruiting
      • Princess Margaret Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada
      • Recruiting
      • McGill University Health Centre Research Institute
• China
  • Changsha, China
    • Active, not recruiting
    • Hunan Cancer Hospital
  • Chengdu, China
    • Active, not recruiting
    • West China Hospital
  • Jinan, China
    • Active, not recruiting
    • Shandong Cancer Hospital
  • Wuhan, China
    • Active, not recruiting
    • Wuhan Union Hospital
  • Zhengzhou, China
    • Active, not recruiting
    • Henan Cancer Hospital
• France
  • Bron, France
    • Recruiting
    • CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
  • Grenoble, France
    • Recruiting
    • CHU de Grenoble - Hôpital Albert Michallon
  • Lyon, France
    • Recruiting
    • Centre Leon Bérard
  • Marseille, France
    • Recruiting
    • Hôpital Nord - CHU Marseille
  • Nantes, France
    • Recruiting
    • ICO - Site René Gauducheau
  • Paris, France
    • Recruiting
    • Hôpital Européen Georges Pompidou
  • Poitiers, France
    • Recruiting
    • CHU Poitiers - Hôpital la Milétrie
  • Reims, France
    • Recruiting
    • Godinot Cancer Institute
  • Rennes, France
    • Recruiting
    • CHU Rennes - Hopital Pontchaillou
  • Villejuif, France
    • Recruiting
    • Institut Gustave Roussy
• Italy
  • Bari, Italy
    • Recruiting
    • Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico
  • Catania, Italy
    • Recruiting
    • Humanitas Istituto Clinico Catanese, Misterbinanoco
  • Milano, Italy
    • Recruiting
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Milano, Italy
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano, Italy
    • Recruiting
    • IEO Istituto Europeo di Oncologia
  • Milano, Italy
    • Recruiting
    • Ospedale San Raffaele
  • Monserrato, Italy
    • Recruiting
    • AOU Cagliari- P.O. Policlinico Universitario Duilio Casula
  • Napoli, Italy
    • Recruiting
    • Azienda Ospedaliera Universitaria- Università degli Studi della Campania
  • Roma, Italy
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Japan
  • Fukuoka, Japan
    • Recruiting
    • National Hospital Organization Kyushu Cancer Center
  • Kashiwa, Japan
    • Recruiting
    • National Cancer Center Hospital East
  • Miyagi, Japan
    • Recruiting
    • Sendai Kousei Hospital
  • Nagoya, Japan
    • Recruiting
    • Aichi Cancer Center Hospital
  • Osaka, Japan
    • Recruiting
    • Kindai University Hospital
  • Shizuoka, Japan
    • Recruiting
    • Shizuoka Cancer Center
  • Tokyo, Japan
    • Recruiting
    • National Cancer Center Hospital
  • Tokyo, Japan
    • Recruiting
    • The Cancer Institute Hospital of JFCR
• Korea, Republic of
  • Busan, Korea, Republic of, 612-022
    • Active, not recruiting
    • Pusan National University Hospital
  • Gyeongsang, Korea, Republic of, 999007
    • Active, not recruiting
    • Pusan National University Yangsan Hospital
  • Hwasun, Korea, Republic of, 540-742
    • Recruiting
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 05742
    • Active, not recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 130-875
    • Active, not recruiting
    • Korea University Guro Hospital
• Poland
  • Poznań, Poland
    • Active, not recruiting
    • Med-Polonia Sp. z o.o.
  • Toruń, Poland
    • Active, not recruiting
    • MICS Centrum Medyczne Toruńa
  • Łódź, Poland
    • Active, not recruiting
    • Instytut Centrum Zdrowia Matki Polki
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Recruiting
    • ICO l'Hospitalet - Hospital Duran i Reynals L'Hospitalet de Llobregat
  • Barcelona, Spain
    • Recruiting
    • Hospital Quirónsalud Barcelona
  • Barcelona, Spain
    • Recruiting
    • Hospital General de Catalunya
  • Barcelona, Spain
    • Recruiting
    • Clínica Mi Tres Torres
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Clinico San Carlos
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Quirónsalud Madrid
  • Málaga, Spain
    • Recruiting
    • Hospital Regional Universitario de Málaga
  • Sevilla, Spain
    • Recruiting
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain
    • Recruiting
    • Hospital Clinico Universitario De Valencia
  • Valencia, Spain
    • Recruiting
    • Instituto Valenciano de Oncologia IVO
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Beverly Hills Cancer Center
    • La Jolla, California, United States, 92037
      • Recruiting
      • Moores Cancer Center at UC San Diego
    • Los Angeles, California, United States, 90089
      • Recruiting
      • Keck Medicine of University of Southern California
    • Orange, California, United States, 92868
      • Recruiting
      • UCI Medical Center
      • Contact: Misako Nagasaka, MD; Phone Number: 714-456-5153; Email: nagasakm@hs.uci.edu
    • Oxnard, California, United States, 93030
      • Recruiting
      • PMK Medical Group Inc
    • Whittier, California, United States, 90601
      • Recruiting
      • American Institute of Research
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Recruiting
      • SCRI - Florida Cancer Specialists South
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Memorial Healthcare System
    • Jacksonville, Florida, United States, 92868
      • Recruiting
      • Cancer Specialists of North Florida
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Recruiting
      • SCRI - Hematology Oncology Clinic
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Recruiting
      • Mayo Clinic
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • Active, not recruiting
      • Center for Cancer Research
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Foundation
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI - Tennessee Oncology
  • Texas
    • Dallas, Texas, United States, 75001
      • Recruiting
      • Renovatio Clinical
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology, P.A.
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77056
      • Recruiting
      • Renovatio Clinical - The Woodlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion 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 or other solid tumors.
3. Evidence of ROS1 fusion by a validated assay.
4. Patients with central nervous system (CNS) involvement, including leptomeningeal carcinomatosis, must be stable, either asymptomatic or previously treated and controlled within 14 days of first dose.
5. The patient can be either ROS1 TKI treatment naïve or treated with prior ROS1 TKI(s).
6. The patient must have at least 1 measurable disease per RECIST 1.1 as assessed by the investigator.
7. Eastern Cooperative Oncology Group Performance Status: 0 or 1.
8. Patient with a life expectancy ≥12 weeks based on the judgement of investigator.

9. 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

10. Patients must be able to practice required contraception during the study.

    1. For males (irrespective of surgical sterilization [vasectomy]): agree to use effective contraception methods during the study intervention period and for at least 90 days after the last dose of investigational drug or agree with complete abstinence.
    2. Females without menses for at least 1 year prior to screening or documented to be surgically sterilized. Women of childbearing potential (WOCBP) must agree to use two concurrent highly effective methods of contraception or agree with complete abstinence from sexual intercourse since the informed consent until 45 days after the last dose of investigational drug. The patient is willing and capable to give written informed consent.
11. The patient is willing and capable to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
12. The patient is willing and capable to comply with study site's COVID-19 policies.

Exclusion Criteria

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; Treatment with immuno-oncology (IO) 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.

   • Placement of vascular access device is not considered major surgery. Other minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.

3. Radiotherapy within 14 days before study treatment. Stereotactic radiosurgery (SRS), stereotactic radiation therapy (SRT), and palliative radiation outside the chest and brain are allowed but must be completed 1 week before starting study treatment.
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.
8. 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.
10. Clinically significant cardiovascular diseases within 3 months prior to the first dose of taletrectinib: myocardial infarction, severe/unstable angina, coronary/peripheral endovascular treatment, heart failure or cerebrovascular disorder including transient ischemic attack.
11. Ongoing cardiac dysrhythmias of ≥ CTCAE Grade 2, uncontrolled atrial fibrillation of any grade, or QT interval corrected for heart rate by Fredericia's formula (QTcF) >470 milliseconds, or symptomatic bradycardia <45 beats per minute; patient has family or medical history of long QT syndrome.
12. Pregnancy or lactation/breastfeeding.
13. Use of food or drugs that are known potent cytochrome P450 3A4/5 (CYP3A4/5) inhibitors or inducers or P-glycoprotein inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment.
14. Administration of agents with potential QT interval prolonging effect within 14 days prior to first dose of study treatment and while on treatment.
15. Patients with other severe medical or mental diseases in whom the risk is increased by the participation to the study or treatment with study treatment in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Taletrectinib; Single-arm trial whereby all consented, enrolled, eligible patients receive taletrectinib	Drug: Taletrectinib; 400mg or 600mg QD; Other Names: DS-6051b; AB-106

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS according to RECIST 1.1 assessed by IRC	Up to 4 years
Objective response rate (ORR) assessed by investigators	ORR according to RECIST 1.1 assessed by investigators	Up to 4 years
Safety and tolerability of taletrectinib	Incidence of Adverse events (AEs), incidence of laboratory abnormalities, incidence of abnormal vital signs, abnormal ECG and abnormal ophthalmologic findings	Up to 4 years
Pharmacokinetic (PK) profile of taletrectinib	Maximum Plasma Concentration (Cmax) of taletrectinib	Up to 4 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial progression-free survival (IC-PFS)	Confirmed IC-PFS per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria	Up to 4 years
Intracranial objective response rate (IC-ORR)	Confirmed IC-ORR per RANO-BM criteria	Up to 4 years

Collaborators and Investigators

• Sponsor: AnHeart Therapeutics Inc.
• Investigators: Study Director: Lian Li, AnHeart Therapeutics Inc.

Publications and helpful links

General Publications

• Bertram JE, Kryah R, Vandermause R, Ean N, Paul R, Carrico A, Sophal C, Bruce S, Gregory K, Stein E, Mannarino J. "No matter what, we just work with the trauma...": Mental Health Therapists' Care of Diverse Sexual and Gender Identity Citizens in Cambodia. Res Sq. 2023 Feb 20:rs.3.rs-2584144. doi: 10.21203/rs.3.rs-2584144/v1. Preprint.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 27, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 9, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: AB-106-G208

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No