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RECRUITING

NCT03093116

PHASE1/PHASE2

A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

Sponsor: Turning Point Therapeutics, Inc.

View on ClinicalTrials.gov

Summary

Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.

Official title: A Phase 1/2, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)

Key Details

Gender

All

Age Range

12 Years - Any

Study Type

INTERVENTIONAL

Enrollment

500

Start Date

2017-03-07

Completion Date

2028-02-29

Last Updated

2026-04-03

Healthy Volunteers

Conditions

Locally Advanced Solid Tumors Metastatic Solid Tumors

Interventions

DRUG

Oral repotrectinib (TPX-0005)

Oral repotrectinib (TPX-0005) capsules.

PHASE 1 Key Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests. 2. ECOG PS 0-1. 3. Age ≥18 (or age ≥ 20 of age as required by local regulation). 4. Capability to swallow capsules intact (without chewing, crushing, or opening). 5. At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed. 6. Prior cytotoxic chemotherapy is allowed. 7. Prior immunotherapy is allowed. 8. Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1. 9. Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria. 10. Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation 11. Life expectancy ≥ 3 months. PHASE 2 Key Inclusion Criteria 1. Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion. 2. Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either: 1. a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility. • Adequate tumor tissue needs to be sent to the Sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the Sponsor. OR 2. a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility. * Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. 4. Age ≥12 (or age ≥ 20 as required by local regulation). 5. Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17. 6. At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible. 7. Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met. i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv. EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+ solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors 8. Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria. 9. Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance \> 40 mL/min; Total serum bilirubin \< 1.5 × ULN; Liver transaminases (ASTs/ALTs) \< 2.5 × ULN; \< 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); \< 2.5 × ULN; \< 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation 10. Life expectancy ≥ 3 months. Key Exclusion Criteria PHASE 1 and PHASE 2 1. Concurrent participation in another therapeutic clinical trial. 2. Symptomatic brain metastases or leptomeningeal involvement. 3. History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years. 4. Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry 5. Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2 6. Any of the following cardiac criteria: Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) \> 470 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval. 7. Known active infections (bacterial, fungal, viral including HIV positivity). 8. Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption. 9. Peripheral neuropathy of CTCAE ≥grade 2. 10. History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.

Locations (165)

Local Institution - 2129

Duarte, California, United States

Local Institution - 2120

Glendale, California, United States

Local Institution - 2136

La Jolla, California, United States

Local Institution - 2114

La Jolla, California, United States

Local Institution - 2121

Long Beach, California, United States

Local Institution - 1001

Orange, California, United States

Local Institution - 2101

Orange, California, United States

St Joseph Heritage Healthcare

Santa Rosa, California, United States

Local Institution - 1003

Aurora, Colorado, United States

Local Institution - 2103

Aurora, Colorado, United States

Local Institution - 2106

Washington D.C., District of Columbia, United States

Local Institution - 2110

Washington D.C., District of Columbia, United States

Memorial Healthcare System

Hollywood, Florida, United States

Local Institution - 2113

Tampa, Florida, United States

University Cancer and Blood Center

Athens, Georgia, United States

Local Institution - 2134

Columbus, Georgia, United States

University of Chicago

Chicago, Illinois, United States

Local Institution - 2142

Peoria, Illinois, United States

Local Institution - 2116

New Orleans, Louisiana, United States

Local Institution - 2133

Baltimore, Maryland, United States

Massachusetts General Hospital,

Boston, Massachusetts, United States

Local Institution - 1004

Boston, Massachusetts, United States

Local Institution - 2131

Boston, Massachusetts, United States

Local Institution - 2105

Ann Arbor, Michigan, United States

Local Institution - 2111

Detroit, Michigan, United States

Local Institution - 2140

Detroit, Michigan, United States

Local Institution - 2132

Saint Paul, Minnesota, United States

Local Institution - 2147

Bolivar, Missouri, United States

Washington University Infusion Center Pharmacy

St Louis, Missouri, United States

Local Institution - 2122

New Brunswick, New Jersey, United States

Local Institution - 2117

New York, New York, United States

Local Institution - 1002

New York, New York, United States

Local Institution - 2102

New York, New York, United States

Local Institution - 2144

Goldsboro, North Carolina, United States

Local Institution - 2112

Canton, Ohio, United States

Local Institution - 2143

Cincinnati, Ohio, United States

Local Institution - 2109

Cleveland, Ohio, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Local Institution - 2119

Toledo, Ohio, United States

Local Institution - 2108

Philadelphia, Pennsylvania, United States

Baptist Memorial Hospital Baptist Cancer Center

Memphis, Tennessee, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Local Institution - 2127

Houston, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Local Institution - 2146

Kingwood, Texas, United States

Local Institution - 2137

Fairfax, Virginia, United States

Local Institution - 2107

Seattle, Washington, United States

Local Institution - 2141

Tacoma, Washington, United States

Local Institution - 2145

Appleton, Wisconsin, United States

Chris O'Brien LifeHouse

Camperdown, New South Wales, Australia

Local Institution - 6103

Adelaide, South Australia, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Local Institution - 3301

East Melbourne, Australia

Local Institution - 4802

Antwerp, Belgium

Local Institution - 4801

Leuven, Belgium

Local Institution - 2202

Edmonton, Alberta, Canada

Local Institution - 2205

Vancouver, British Columbia, Canada

Local Institution - 2201

Toronto, Ontario, Canada

Local Institution - 6503

Toronto, Ontario, Canada

Local Institution - 2203

Ontario, Canada

Local Institution - 2204

Ottawa, Canada

Local Institution - 6702

Beijing, Beijing Municipality, China

Beijing Cancer hospital

Beijing, Beijing Municipality, China

Daping Hospital, the Third Affiliated Hospital of Third Military Medical University /Cancer Center

Daping, Chongqing Municipality, China

Local Institution - 6719

Fuzhou, Fujian, China

The First Affiliated hospital of Xiamen University-oncology

Xiamen, Fujian, China

Guangdong Provincial People'S Hospital

Guangzhou, Guangdong, China

Local Institution - 6733

Guangzhou, Guangdong, China

Local Institution - 6505

Shenzhen, Guangdong, China

The Affiliated Tumor Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Local Institution - 6504

Shatin, HONG KONG, China

Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology/Cancer Center Department

Wuhan, Hubei, China

Local Institution - 6705

Changsha, Hunan, China

Hunan Cancer Hospital-thoracic oncology II

Changsha, Hunan, China

Local Institution - 6748

Nanjing, Jiangsu, China

XuZhou Central Hospital/Oncology Department

Xuzhou, Jiangsu, China

Jilin Cancer Hospital/Medical Oncology Department

Changchun, Jilin, China

Jilin Cancer Hospital/Medical Oncology Department

Changchun, Jilin, China

The first hospital of Jilin university-Oncology Department

Changchun, Jilin, China

Liaoning Cancer Hospital

Shenyang, Liaoning, China

Tangdu Hospital

Xi'an, Shan3xi, China

Shanxi Bethune Hospital

Taiyuan, Shanxi, China

Sichuan Cancer Hospital/Medical Oncology Department

Chengdu, Sichuan, China

The First Hospital Affiliated To AMU - Southwest Hospital

Chongqing, Sichuan, China

Local Institution - 6725

Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital-Oncology

Hangzhou, Zhejiang, China

The Third Xiangya Hospital of Central South University/Department of Respiratory and Critical Care Medicine

Changsha, China

West China Hospital Sichuan University/Lung cancer center

Chengdu, China

The First Affiliated Hospital - Zhejiang University School of Medicine

Hangzhou, China

Anhui Provincial Hospital

Hefei, China

Shanghai Chest Hospital

Shanghai, China

Shanghai Chest Hospital

Shanghai, China

Weifang People's Hospital/Medical Oncology Department

Weifang, China

Henan Cancer Hospital/The 1st pneumology department

Zhengzhou, China

Local Institution - 4901

Copenhagen, Denmark

Local Institution - 4201

Marseille, Bouches-du-Rhône, France

Local Institution - 4207

Brest, France

Centre Georges-Francois Leclerc

Dijon, France

Centre Hospitalier Universitarie Grenoble Alpes (Chuga)

Grenoble, France

Centre Antoine-Lacassagne

Nice, France

Local Institution - 4208

Poitiers, France

Local Institution - 4203

Saint-Mandé, France

Institute Gustave Roussy

Villejuif, France

Local Institution - 4704

Berlin, Germany

Local Institution - 4701

Cologne, Germany

Local Institution - 4703

Dresden, Germany

Local Institution - 4702

Heidelberg, Germany

Local Institution - 6502

Hong Kong, Hong Kong

Local Institution - 6501

Hong Kong, Hong Kong

Local Institution - 5101

Budapest, Hungary

Local Institution - 5103

Budapest, Hungary

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, MI, Italy

Local Institution - 4306

Milan, Italy

Local Institution - 4307

Palermo, Italy

Centro di Riferimento Oncologico

Pordenone, Italy

Local Institution - 4304

Ravenna, Italy

Local Institution - 4305

Reggio Emilia, Italy

IRCCS Istituto Regina Elena Oncologia Medica 2

Roma, Italy

Local Institution - 4302

Terni, Italy

Ehime University Hospital

Tōon, Ehime, Japan

Hokkaido University Hospital

Sapporo, Hokkaido, Japan

Kanagawa cancer center

Yokohama, Kanagawa, Japan

Osaka City General Hospital

Osaka, Osaka, Japan

National Cancer Center Hospital.

Chuo-ku, Tokyo, Japan

Tottori University Hospital

Yonago, Tottori, Japan

National Cancer Center Hospital East

Kashiwa, Japan

Nagoya University Hospital

Nagoya, Japan

Osaka International Cancer institute

Osaka, Japan

Local Institution - 4502

Amsterdam, Netherlands

Local Institution - 4501

Groningen, Netherlands

Ośrodek Badań Klinicznych Wczesnych Faz, Uniwersyteckie Centrum Kliniczne

Gdansk, Poland

Local Institution - 4604

Lublin, Poland

Local Institution - 4605

Poznan, Poland

Local Institution - 4603

Szczecin, Poland

Local Institution - 4602

Warsaw, Poland

National University Hospital

Singapore, Singapore

National Cancer Center Singapore

Singapore, Singapore

Local Institution - 3003

Seoul, Gangnam-gu, South Korea

Chonnam National University Hwasun Hospital

Hwasun-eup, Hwasun-gun, Jeollanam-do, South Korea

Local Institution - 3002

Seoul, Seodaemun-gu, South Korea

Local Institution - 3002

Seoul, Seoul Teugbyeolsi, South Korea

Seoul National University Hospital

Seoul, Seoul-teukbyeolsi [Seoul], South Korea

Samsung Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], South Korea

Local Institution - 6306

Cheongju-si, South Korea

Local Institution - 3001

Seoul, South Korea

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Local Institution - 6307

Seoul, South Korea

Asan Medical Center

Seoul, South Korea

Local Institution - 6304

Seoul, South Korea

Local Institution - 4102

Barcelona, Spain

Hospital Unversitario Val D'Hebrón

Barcelona, Spain

Local Institution - 4106

Madrid, Spain

START Madrid-FJD

Madrid, Spain

Local Institution - 4103

Madrid, Spain

Hospital Universitario HM Sanchinarro CIOCC

Madrid, Spain

Local Institution - 4108

Pamplona, Spain

Local Institution - 4107

Valencia, Spain

Local Institution - 6201

Taiepi, Taiwan

Local Institution - 6203

Tainan, Taiwan

Local Institution - 6202

Taipei, Taiwan

Local Institution - 4401

London, United Kingdom

Local Institution - 4402

London, United Kingdom

Local Institution - 4404

London, United Kingdom

Local Institution - 4403

Manchester, United Kingdom

Local Institution - 4405

Sutton, United Kingdom

Clinical Research Directory

A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (165)