Taletrectinib Phase 2 Global Study in ROS1 Positive NSCLC

Non Small Cell Lung Cancer Clinical Trial

— TRUST-II  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04919811
• Other study ID #: AB-106-G208
• Status: Recruiting
• Phase: Phase 2
• Start date: September 1, 2021
• Est. completion date: June 2027

Study information

• Verified date: February 2024
• Source: AnHeart Therapeutics Inc.
• Contact: Lian Li
• Phone: +1 212-466-6378
• Email: trials[@]anhearttherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 224
• Est. completion date: June 2027
• Est. primary completion date: June 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung Cancer

Intervention

Drug:
• Taletrectinib
400mg or 600mg QD

Locations

Country	Name	City	State
Canada	McGill University Health Centre Research Institute	Montréal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
China	Hunan Cancer Hospital	Changsha
China	West China Hospital	Chengdu
China	Shandong Cancer Hospital	Jinan
China	Wuhan Union Hospital	Wuhan
China	Henan Cancer Hospital	Zhengzhou
France	CHU Lyon - Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel	Bron
France	CHU de Grenoble - Hôpital Albert Michallon	Grenoble
France	Centre Léon Bérard	Lyon
France	Hôpital Nord - CHU Marseille	Marseille
France	ICO - Site René Gauducheau	Nantes
France	Hôpital Européen Georges Pompidou	Paris
France	CHU Poitiers - Hopital la Miletrie	Poitiers
France	Godinot Cancer Institute	Reims
France	CHU Rennes - Hopital Pontchaillou	Rennes
France	Institut Gustave Roussy	Villejuif
Italy	Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico	Bari
Italy	Humanitas Istituto Clinico Catanese, Misterbinanoco	Catania
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	IEO Istituto Europeo di Oncologia	Milano
Italy	Ospedale San Raffaele	Milano
Italy	AOU Cagliari- P.O. Policlinico Universitario Duilio Casula	Monserrato
Italy	Azienda Ospedaliera Universitaria- Università degli Studi della Campania	Napoli
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa
Japan	Sendai Kousei Hospital	Miyagi
Japan	Aichi Cancer Center Hospital	Nagoya
Japan	Kindai University Hospital	Osaka
Japan	Shizuoka Cancer Center	Shizuoka
Japan	National Cancer Center Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Pusan National University Yangsan Hospital	Gyeongsang
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Poland	Instytut Centrum Zdrowia Matki Polki	Lódz
Poland	Med-Polonia Sp. z o.o.	Poznan
Poland	MICS Centrum Medyczne Toruna	Torun
Spain	Clinica Mi Tres Torres	Barcelona
Spain	Hospital General de Catalunya	Barcelona
Spain	Hospital Quironsalud Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	ICO l'Hospitalet - Hospital Duran i Reynals L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Quironsalud Madrid	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Regional Universitario de Malaga	Málaga
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Instituto Valenciano de Oncologia IVO	Valencia
United States	SCRI - Hematology Oncology Clinic	Baton Rouge	Louisiana
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Center for Cancer Research	Brick	New Jersey
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Renovatio Clinical	Dallas	Texas
United States	Texas Oncology, P.A.	Dallas	Texas
United States	SCRI - Florida Cancer Specialists South	Fort Myers	Florida
United States	Memorial Healthcare System	Hollywood	Florida
United States	MD Anderson Cancer Center	Houston	Texas
United States	Renovatio Clinical - The Woodlands	Houston	Texas
United States	Cancer Specialists of North Florida	Jacksonville	Florida
United States	Moores Cancer Center at UC San Diego	La Jolla	California
United States	Keck Medicine of University of Southern California	Los Angeles	California
United States	SCRI - Tennessee Oncology	Nashville	Tennessee
United States	UCI Medical Center	Orange	California
United States	PMK Medical Group Inc	Oxnard	California
United States	Mayo Clinic	Rochester	Minnesota
United States	American Institute of Research	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
AnHeart Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Canada,  China,  France,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Intracranial progression-free survival (IC-PFS)	Confirmed IC-PFS per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria	Up to 4 years
Other	Intracranial objective response rate (IC-ORR)	Confirmed IC-ORR per RANO-BM criteria	Up to 4 years
Primary	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	Progression-free survival (PFS)	PFS according to RECIST 1.1 assessed by IRC	Up to 4 years
Secondary	Objective response rate (ORR) assessed by investigators	ORR according to RECIST 1.1 assessed by investigators	Up to 4 years
Secondary	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
Secondary	Pharmacokinetic (PK) profile of taletrectinib	Maximum Plasma Concentration (Cmax) of taletrectinib	Up to 4 years