AzTrials
AzTrials

Locally Advanced Solid TumorsPhase 1/2TRIDENT-1NCT03093116

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

A Phase 1/2 study testing Oral repotrectinib (TPX-0005) in people with Locally Advanced Solid Tumors and Metastatic Solid Tumors, run by Turning Point Therapeutics, Inc. at 165 sites in 19 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Oral repotrectinib (TPX-0005)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
500 participants
Where
165 sitesin 19 countries
Study dates
7 Mar 2017to 29 Feb 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
  • ECOG PS 0-1.
  • Age ≥18 (or age ≥ 20 of age as required by local regulation).
  • Capability to swallow capsules intact (without chewing, crushing, or opening).
  • 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.
  • Prior cytotoxic chemotherapy is allowed.
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  • Prior immunotherapy is allowed.
  • 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.
  • Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
  • 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
  • Life expectancy ≥ 3 months.
  • PHASE 2 Key Inclusion Criteria
  • 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.
  • Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
  • 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
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
  • Age ≥12 (or age ≥ 20 as required by local regulation).
  • 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.
  • 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.
  • 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.
  • 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
  • Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
  • 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
  • Life expectancy ≥ 3 months.

Who cannot join

  • Concurrent participation in another therapeutic clinical trial.
  • Symptomatic brain metastases or leptomeningeal involvement.
  • 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.
  • 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
  • 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
  • Any of the following cardiac criteria:
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  • 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.
  • Known active infections (bacterial, fungal, viral including HIV positivity).
  • Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
  • Peripheral neuropathy of CTCAE ≥grade 2.
  • 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.

Trial locations and contacts

165 sites in 19 countries. Contact the study team or a site near you to ask about taking part.

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com contact

855-907-3286

Clinical.Trials@bms.com

First line of the email MUST contain NCT # and Site #. contact

165 sites in 19 countries

United States49 sites, 11 recruiting

  • Local Institution - 2105

    Ann Arbor, Michigan, 48109

    Completed

  • Local Institution - 2145

    Appleton, Wisconsin, 54911

    Completed

  • University Cancer and Blood Center

    Athens, Georgia, 30607

    PETROS NIKOLINAKOS, Site 2139, 706-353-2990

    Recruiting

  • Local Institution - 1003

    Aurora, Colorado, 80045

    Completed

  • Local Institution - 2103

    Aurora, Colorado, 80045

    Completed

  • Local Institution - 2133

    Baltimore, Maryland, 21210

    Completed

  • Local Institution - 2147

    Bolivar, Missouri, 65613

    Completed

  • Massachusetts General Hospital,

    Boston, Massachusetts, 02114

    Jessica Lin, Site 2104, 617-724-4000

    Recruiting

  • Local Institution - 1004

    Boston, Massachusetts, 02214

    Completed

  • Local Institution - 2131

    Boston, Massachusetts, 02215

    Completed

  • Local Institution - 2112

    Canton, Ohio, 44718

    Completed

  • University of Chicago

    Chicago, Illinois, 60637

    Christine Bestvina, Site 2125, 773-702-4400

    Recruiting

  • Local Institution - 2143

    Cincinnati, Ohio, 45220

    Completed

  • Local Institution - 2109

    Cleveland, Ohio, 44195

    Completed

  • Local Institution - 2134

    Columbus, Georgia, 31904

    Completed

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

    Dwight Owen, Site 2123, 614-293-6401

    Recruiting

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

    Syed Kazmi, Site 2130, 214-648-5368

    Recruiting

  • Local Institution - 2111

    Detroit, Michigan, 48201

    Completed

  • Local Institution - 2140

    Detroit, Michigan, 48202-2608

    Completed

  • Local Institution - 2129

    Duarte, California, 91010

    Completed

  • Local Institution - 2137

    Fairfax, Virginia, 22031

    Completed

  • Local Institution - 2120

    Glendale, California, 91206

    Completed

  • Local Institution - 2144

    Goldsboro, North Carolina, 27534

    Completed

  • Memorial Healthcare System

    Hollywood, Florida, 33021

    Luis Raez, Site 2128, 954-265-4325

    Recruiting

  • Local Institution - 2127

    Houston, Texas, 77030

    Completed

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    George Blumenschein Jr, Site 2138, 713-792-6363

    Recruiting

  • Local Institution - 2146

    Kingwood, Texas, 77339

    Completed

  • Local Institution - 2136

    La Jolla, California, 92037

    Withdrawn

  • Local Institution - 2114

    La Jolla, California, 92093

    Completed

  • Local Institution - 2121

    Long Beach, California, 90813

    Completed

  • Baptist Memorial Hospital Baptist Cancer Center

    Memphis, Tennessee, 38120

    Philip Lammers, Site 2148

    Recruiting

  • Local Institution - 2122

    New Brunswick, New Jersey, 08901

    Completed

  • Local Institution - 2116

    New Orleans, Louisiana, 70121

    Site 2116

    Not yet recruiting

  • Local Institution - 2117

    New York, New York, 10016

    Completed

  • Local Institution - 1002

    New York, New York, 10065

    Active, not recruiting

  • Local Institution - 2102

    New York, New York, 10065

    Completed

  • Local Institution - 1001

    Orange, California, 92868

    Completed

  • Local Institution - 2101

    Orange, California, 92868

    Completed

  • Local Institution - 2142

    Peoria, Illinois, 61615

    Completed

  • Local Institution - 2108

    Philadelphia, Pennsylvania, 19111-2497

    Completed

  • Local Institution - 2132

    Saint Paul, Minnesota, 55101

    Completed

  • St Joseph Heritage Healthcare

    Santa Rosa, California, 95403

    Ian Anderson, Site 2126

    Recruiting

  • Local Institution - 2107

    Seattle, Washington, 98109

    Completed

  • Washington University Infusion Center Pharmacy

    St Louis, Missouri, 63110

    Brian Van Tine, Site 2115, 314-747-3096

    Recruiting

  • Local Institution - 2141

    Tacoma, Washington, 98405

    Withdrawn

  • Local Institution - 2113

    Tampa, Florida, 33612

    Completed

  • Local Institution - 2119

    Toledo, Ohio, 43614

    Completed

  • Local Institution - 2106

    Washington D.C., District of Columbia, 20007

    Completed

  • Local Institution - 2110

    Washington D.C., District of Columbia, 20016

    Completed

Other trials in United States

China33 sites, 24 recruiting

  • Local Institution - 6702

    Beijing, Beijing Municipality, 100021

    Completed

  • Beijing Cancer hospital

    Beijing, Beijing Municipality, 100142

    Jian Fang, Site 6703, 868613701224460

    Recruiting

  • Jilin Cancer Hospital/Medical Oncology Department

    Changchun, Jilin, 130012

    Meili Sun, Site 6720, 18953116532

    Recruiting

  • Jilin Cancer Hospital/Medical Oncology Department

    Changchun, Jilin, 130012

    Ying Cheng, Site 6717, 8613943012851

    Recruiting

  • The first hospital of Jilin university-Oncology Department

    Changchun, Jilin, 130021

    Jiuwei Cui, Site 6714, 8615843073215

    Recruiting

  • Local Institution - 6705

    Changsha, Hunan, 410011

    Completed

  • Hunan Cancer Hospital-thoracic oncology II

    Changsha, Hunan, 410013

    Nong Yang, Site 6718, 13055193557

    Recruiting

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

    Changsha, 00000

    Jie Meng, Site 6734

    Recruiting

  • Sichuan Cancer Hospital/Medical Oncology Department

    Chengdu, Sichuan, 00000

    Wenxiu Yao, Site 6728, 18908178836

    Recruiting

  • West China Hospital Sichuan University/Lung cancer center

    Chengdu, 00000

    Feng Luo, Site 6724, +8618980601766

    Recruiting

  • The First Hospital Affiliated To AMU - Southwest Hospital

    Chongqing, Sichuan, 400030

    Liang Gong, Site 6716, +8613983965893

    Recruiting

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

    Daping, Chongqing Municipality, 00000

    Yong He, Site 6736, 13908338998

    Recruiting

  • Local Institution - 6719

    Fuzhou, Fujian, 000000

    Completed

  • Guangdong Provincial People'S Hospital

    Guangzhou, Guangdong, 510120

    Jinji Yang, Site 6747

    Recruiting

  • Local Institution - 6733

    Guangzhou, Guangdong, 510120

    Completed

  • Local Institution - 6725

    Hangzhou, Zhejiang, 310016

    Completed

  • Zhejiang Cancer Hospital-Oncology

    Hangzhou, Zhejiang, 310022

    Yiping Zhang, Site 6721

    Recruiting

  • The First Affiliated Hospital - Zhejiang University School of Medicine

    Hangzhou, 310003

    Jianying Zhou, Site 6712, 8613505719970

    Recruiting

  • The Affiliated Tumor Hospital of Harbin Medical University

    Harbin, Heilongjiang, 150081

    Yan Yu, Site 6722, 13904505825

    Recruiting

  • Anhui Provincial Hospital

    Hefei, 230001

    Yueyin Pan, Site 6704, 8613805695536

    Recruiting

  • Local Institution - 6748

    Nanjing, Jiangsu, 210008

    Completed

  • Shanghai Chest Hospital

    Shanghai, 200030

    Liyan Jiang, Site 6709

    Recruiting

  • Shanghai Chest Hospital

    Shanghai, 200030

    Shun Lu, Site 6701, 8613601813062

    Recruiting

  • Local Institution - 6504

    Shatin, HONG KONG, 999077

    Active, not recruiting

  • Liaoning Cancer Hospital

    Shenyang, Liaoning, 110801

    Rui Ma, Site 6742

    Recruiting

  • Local Institution - 6505

    Shenzhen, Guangdong, 518053

    Active, not recruiting

  • Shanxi Bethune Hospital

    Taiyuan, Shanxi, 030032

    Junping Zhang, Site 6749, 13994204099

    Recruiting

  • Weifang People's Hospital/Medical Oncology Department

    Weifang, 00000

    Guohua Yu, Site 6727

    Recruiting

  • Local Institution - 6710

    Wuhan, Hubei, 430022

    Completed

  • Tangdu Hospital

    Xi'an, Shan3xi, 710038

    Haichuan Su, Site 6754

    Recruiting

  • The First Affiliated hospital of Xiamen University-oncology

    Xiamen, Fujian, 361003

    Jingxun Wu, Site 6708, 15160085395

    Recruiting

  • XuZhou Central Hospital/Oncology Department

    Xuzhou, Jiangsu, 00000

    Xiang Wang, Site 6732

    Recruiting

  • Henan Cancer Hospital/The 1st pneumology department

    Zhengzhou, 00000

    Xiufeng Hu, Site 6715, +8618339920984

    Recruiting

Other trials in China

South Korea12 sites, 5 recruiting

  • Local Institution - 6306

    Cheongju-si, 28644

    Completed

  • Chonnam National University Hwasun Hospital

    Hwasun-eup, Hwasun-gun, Jeollanam-do, 519-763

    Young-Chul Kim, Site 6308

    Recruiting

  • Local Institution - 3003

    Seoul, Gangnam-gu, 06351

    Completed

  • Local Institution - 3002

    Seoul, Seodaemun-gu, 03722

    Completed

  • Local Institution - 3002

    Seoul, Seoul Teugbyeolsi, 03080

    Withdrawn

  • Seoul National University Hospital

    Seoul, Seoul-teukbyeolsi [Seoul], 03080

    Dong-Wan Kim, Site 6301, +821027324635

    Recruiting

  • Samsung Medical Center

    Seoul, Seoul-teukbyeolsi [Seoul], 06351

    Jung Yong Hong, Site 6303, +82234103459

    Recruiting

  • Local Institution - 3001

    Seoul, 03080

    Completed

  • Yonsei University Health System, Severance Hospital

    Seoul, 03722

    Byoung Chul Cho, Site 6302, 82222288126

    Recruiting

  • Local Institution - 6307

    Seoul, 05030

    Completed

  • Asan Medical Center

    Seoul, 05505

    Sang-We Kim, Site 6305, 82230103215

    Recruiting

  • Local Institution - 6304

    Seoul, 06591

    Completed

Other trials in South Korea

Japan9 sites, 9 recruiting

  • National Cancer Center Hospital.

    Chuo-ku, Tokyo, 1040045

    Yasushi Goto, Site 6604, +819043996497

    Recruiting

  • National Cancer Center Hospital East

    Kashiwa, 277-8577

    Koichi Goto, Site 6601, 81471331111

    Recruiting

  • Nagoya University Hospital

    Nagoya, 466-8560

    Yuichi Ando, Site 6608, 81527412111

    Recruiting

  • Osaka City General Hospital

    Osaka, Osaka, 5340021

    Haruko Daga, Site 6605, 81669293269

    Recruiting

  • Osaka International Cancer institute

    Osaka, 5418567

    Motohiro 基裕 Tamiya 田宮, Site 6602, 81669451181

    Recruiting

  • Hokkaido University Hospital

    Sapporo, Hokkaido, 0608648

    Jun Sakakibara, Site 6607, +81-11-716-1161

    Recruiting

  • Ehime University Hospital

    Tōon, Ehime, 791-0295

    Naoyuki Nogami, Site 6609, +81-89-960-5994

    Recruiting

  • Kanagawa cancer center

    Yokohama, Kanagawa, 2418515

    Kato Terufumi, Site 6603, +8145520222200000000

    Recruiting

  • Tottori University Hospital

    Yonago, Tottori, 683-8504

    Kodani Masahiro, Site 6606

    Recruiting

Other trials in Japan

France8 sites, 4 recruiting

  • Local Institution - 4207

    Brest, 29200

    Completed

  • Centre Georges-Francois Leclerc

    Dijon, 21079

    Alice Hervieu, Site 4204, 33380737506

    Recruiting

  • Centre Hospitalier Universitarie Grenoble Alpes (Chuga)

    Grenoble, 38043

    Denis Moro-Sibilot, Site 4206, 33476768708

    Recruiting

  • Local Institution - 4201

    Marseille, Bouches-du-Rhône, 13005

    Completed

  • Centre Antoine-Lacassagne

    Nice, 06189

    Esma Saada-Bouzid, Site 4205, 33492031514

    Recruiting

  • Local Institution - 4208

    Poitiers, 86000

    Completed

  • Local Institution - 4203

    Saint-Mandé, 94163

    Completed

  • Institute Gustave Roussy

    Villejuif, 98405

    Benjamin Besse, Site 4202, 33142114211

    Recruiting

Other trials in France

Italy8 sites, 4 recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, MI, 20133

    Roberto Ferrara, Site 4301, 390223903829

    Recruiting

  • Local Institution - 4306

    Milan, 20122

    Completed

  • Local Institution - 4307

    Palermo, 90146

    Withdrawn

  • Centro di Riferimento Oncologico

    Pordenone, 33081

    Alessandra Bearz, Site 4303, 390434659294

    Recruiting

  • Local Institution - 4304

    Ravenna, 48121

    Site 4304

    Not yet recruiting

  • Local Institution - 4305

    Reggio Emilia, 42123

    Completed

  • IRCCS Istituto Regina Elena Oncologia Medica 2

    Roma, 144

    Federico Capuzzo, Site 4308, +390516225126

    Recruiting

  • Local Institution - 4302

    Terni, 05100

    Completed

Other trials in Italy

Spain8 sites, 3 recruiting

  • Local Institution - 4102

    Barcelona, 08028

    Completed

  • Hospital Unversitario Val D'Hebrón

    Barcelona, 8035

    Enriqueta Felip, Site 4101

    Recruiting

  • Local Institution - 4106

    Madrid, 28033

    Completed

  • START Madrid-FJD

    Madrid, 28040

    Victor Moreno, Site 4104, 34915504800272400

    Recruiting

  • Local Institution - 4103

    Madrid, 28041

    Completed

  • Hospital Universitario HM Sanchinarro CIOCC

    Madrid, 28050

    Emiliano Calvo, Site 4105, +34934894304

    Recruiting

  • Local Institution - 4108

    Pamplona, 31008

    Completed

  • Local Institution - 4107

    Valencia, 46009

    Completed

Other trials in Spain

Canada6 sites

  • Local Institution - 2202

    Edmonton, Alberta, T6G 1Z2

    Completed

  • Local Institution - 2203

    Ontario, L6R 37R

    Completed

  • Local Institution - 2204

    Ottawa, K1H 8L6

    Completed

  • Local Institution - 2201

    Toronto, Ontario, M5G 2M9

    Completed

  • Local Institution - 6503

    Toronto, Ontario, M5G 2M9

    Active, not recruiting

  • Local Institution - 2205

    Vancouver, British Columbia, V5Z 4E7

    Withdrawn

Other trials in Canada

Poland5 sites, 1 recruiting

  • Ośrodek Badań Klinicznych Wczesnych Faz, Uniwersyteckie Centrum Kliniczne

    Gdansk, 80-214

    Rafal Dziadziuszko, Site 4601, 48585844571

    Recruiting

  • Local Institution - 4604

    Lublin, 20-609

    Completed

  • Local Institution - 4605

    Poznan, 60-693

    Completed

  • Local Institution - 4603

    Szczecin, 70-784

    Completed

  • Local Institution - 4602

    Warsaw, 02-781

    Completed

Other trials in Poland

United Kingdom5 sites

  • Local Institution - 4401

    London, SW3 6JJ

    Completed

  • Local Institution - 4402

    London, W12 OHS

    Completed

  • Local Institution - 4404

    London, W1G 6AD

    Completed

  • Local Institution - 4403

    Manchester, M20 4BX

    Completed

  • Local Institution - 4405

    Sutton, SM2 5PT

    Completed

Other trials in United Kingdom

Australia4 sites, 2 recruiting

  • Local Institution - 6103

    Adelaide, South Australia, 5042

    Completed

  • Chris O'Brien LifeHouse

    Camperdown, New South Wales, 2050

    Steven Kao, Site 6102, 61295157403

    Recruiting

  • Local Institution - 3301

    East Melbourne, 3002

    Completed

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

    Ben Solomon, Site 6101, 61385595000

    Recruiting

Other trials in Australia

Germany4 sites

  • Local Institution - 4704

    Berlin, 13125

    Completed

  • Local Institution - 4701

    Cologne, 50937

    Completed

  • Local Institution - 4703

    Dresden, 01307

    Completed

  • Local Institution - 4702

    Heidelberg, 69120

    Completed

Other trials in Germany

Taiwan3 sites

  • Local Institution - 6201

    Taiepi, 100

    Active, not recruiting

  • Local Institution - 6203

    Tainan, 704

    Active, not recruiting

  • Local Institution - 6202

    Taipei, 10449

    Completed

Other trials in Taiwan

Belgium2 sites

  • Local Institution - 4802

    Antwerp, 2650

    Completed

  • Local Institution - 4801

    Leuven, 3000

    Completed

Other trials in Belgium

Hong Kong2 sites

  • Local Institution - 6502

    Hong Kong, 0

    Active, not recruiting

  • Local Institution - 6501

    Hong Kong

    Active, not recruiting

Other trials in Hong Kong

Hungary2 sites

  • Local Institution - 5101

    Budapest, 1083

    Completed

  • Local Institution - 5103

    Budapest, 1121

    Completed

Other trials in Hungary

Netherlands2 sites

  • Local Institution - 4502

    Amsterdam, 1066 CX

    Completed

  • Local Institution - 4501

    Groningen, 9713 GZ

    Completed

Other trials in Netherlands

Singapore2 sites, 2 recruiting

  • National University Hospital

    Singapore, 119074

    Ross Soo, Site 6401, 000-000-0000

    Recruiting

  • National Cancer Center Singapore

    Singapore, 169610

    Wan Teck Darren Lim, Site 6402, 656564368000

    Recruiting

Other trials in Singapore

Denmark1 site

  • Local Institution - 4901

    Copenhagen, 2100

    Completed

Other trials in Denmark

About this study

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)

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.

Read the detailed description

In Phase 2, study subjects will be enrolled into 6 distinct expansion (EXP) cohorts:

  • EXP-1: ROS1 TKI-naïve ROS1+ NSCLC. Up to one prior line of chemotherapy OR immunotherapy is allowed
  • EXP-2: 1 Prior ROS1 TKI AND 1 Platinum-based Chemotherapy ROS1+ NSCLC. Disease progression, or intolerant to one prior line of a ROS1 TKI. Must have received one prior line of platinum based chemotherapy OR one prior line of platinum based chemotherapy in combination with immunotherapy before or after a ROS1 TKI
  • EXP-3: 2 Prior ROS1 TKIs AND NO Chemotherapy ROS1+ NSCLC. Disease progression, or intolerant to 2 prior lines of a ROS1 TKI treatment. No prior lines of chemotherapy or immunotherapy are allowed.
  • EXP-4: 1 Prior ROS1 TKI and NO Chemotherapy or Immunotherapy. Disease progression or intolerant to one prior line of a ROS1 TKI. No prior lines of chemotherapy or immunotherapy are allowed.
  • EXP-5: TRK TKI-naïve NTRK+ solid tumors. Any number of prior lines of chemo or immunotherapy is allowed.
  • EXP-6: TRK TKI-pretreated NTRK+ solid tumors. Disease progression, or intolerant to 1 or 2 prior TRK TKIs. Any number of prior lines of chemo- or immunotherapy are allowed.
Being tested
Oral repotrectinib (TPX-0005)
Keywords
ALK, ROS1, NTRK, Sarcoma, Lung Neoplasms, Carcinoma, NSCL, NSCLC, Non Small Cell Lung, Thyroid Disease, Colonic Neoplasms, Thyroid Neoplasms, Carcinoma, Neuroendocrine, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Disease, Respiratory Tract Disease, Carcinoma, Bronchogenic, Bronchial Neoplasms
Medical subject headings
Sarcoma, Lung Neoplasms, Carcinoma, Thyroid Diseases, Colonic Neoplasms, Thyroid Neoplasms, Carcinoma, Neuroendocrine, Respiratory Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral repotrectinib (TPX-0005)Drug

    Also called repotrectinib

    Oral repotrectinib (TPX-0005) capsules.

Study groups in NCT03093116
Study groupRoleWhat they receive
Repotrectinib (TPX-0005)ExperimentalPhase 1 Oral repotrectinib (TPX-0005): Phase 1a dose escalation, Phase 1b food-effect sub-study, and Phase 1c dose escalation with food, and Midazolam drug-drug interaction sub-study. Phase 2 Oral repotrectinib (TPX-0005): 6 distinct expansion cohorts * EXP-1: ROS1 TKI-naïve ROS1+ NSCLC * EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC * EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) * EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) * EXP-5: TRK TKI-naïve NTRK+ solid tumors * EXP-6: TRK TKI-pretreated NTRK+ solid tumors
Receives: Drug: Oral repotrectinib (TPX-0005)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicities (DLTs) (Phase 1)

    Define the dose limiting toxicities (DLTs) (Phase 1)

    Measured: Within 28 days of the first repotrectinib dose

  2. Recommended Phase 2 Dose (RP2D) (Phase 1)

    To determine the RP2D (Phase 1)

    Measured: Within 28 days of the last patient dosed in escalation

  3. Overall Response Rate (ORR) Phase 2

    To determine the confirmed ORR of repotrectinib (TPX-0005) as assessed by Blinded Independent Central Review (Phase 2)

    Measured: Two to three years after first dose of repotrectinib dose

Secondary outcomes (13)

  1. Maximum plasma concentration (CMAX) of repotrectinib (TPX-0005) (Phase 1)

    To determine the maximum plasma concentration (CMAX) of repotrectinib (TPX-0005)

    Measured: Up to 72 hours post dose

  2. Area under the plasma concentration time curve (AUC) of repotrectinib (TPX-0005) (Phase 1)

    To determine the area under the plasma concentration time curve (AUC) of repotrectinib

    Measured: Up to 72 hours post dose

  3. Area under the plasma concentration time curve (AUC) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1)

    To determine the area under the plasma concentration time curve (AUC) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1)

    Measured: Up to 72 hours post dose

  4. Maximum plasma concentration (CMAX) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1)

    To determine the maximum plasma concentration (CMAX) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1)

    Measured: Up to 72 hours post dose

  5. Area under the plasma concentration time curve (AUC) of midazolam(TPX-0005) (Phase 1)

    To determine the area under the plasma concentration time curve (AUC) of midazolam(TPX-0005) (Phase 1)

    Measured: Up to 24 hours post dose

  6. Maximum plasma concentration (CMAX) of midazolam(TPX-0005) (Phase 1)

    To determine the maximum plasma concentration (CMAX) of midazolam(TPX-0005) (Phase 1)

    Measured: Up to 24 hours post dose

  7. Plasma concentration of repotrectinib following administration at RP2D (Phase 2)

    To evaluate the plasma concentration of repotrectinib following administration at RP2D (Phase 2)

    Measured: Pre dose and 4 hours post dose

  8. Preliminary objective response rate (ORR) (Phase 1)

    To determine the preliminary objective response rate (ORR) by Blinded Independent Central Review (BICR) (Phase 1)

    Measured: Approximately three years

  9. Duration of response (DOR) (Phase 2)

    To determine the DOR of repotrectinib (TPX-0005) (Phase 2)

    Measured: Approximately three years

  10. Clinical benefit rate (CBR) (Phase 2)

    To determine the CBR of repotrectinib (TPX-0005) (Phase 2)

    Measured: Approximately three years

  11. Progression free survival (PFS) (Phase 2)

    To determine the PFS (Phase 2)

    Measured: Approximately three years

  12. Overall survival (OS) (Phase 2)

    To determine the OS (Phase 2)

    Measured: Approximately three years

  13. Intracranial objective response rate (Phase 2)

    To determine the intracranial objective response rate (Phase 2)

    Measured: Approximately three years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2017
  2. Study start7 Mar 2017
  3. Primary completion29 Feb 2028 (estimated)
  4. Study completion29 Feb 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
500 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03093116
Sponsor's protocol ID
CA127-1024
Other IDs
CA127-1024, TPX-0005-01
Acronym
TRIDENT-1
Status last verified
May 2026
First submitted
6 Mar 2017
Last updated
27 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Expanded access
Available

Publications

  • Besse B, Lin JJ, Bazhenova L, Goto K, de Langen AJ, Kim DW, Wolf J, Springfeld C, Popat S, Lim DWT, Nagasaka M, Hong JY, Baik CS, Hervieu A, Moreno V, Yang N, Kollengode K, Yang H, Xu Y, Calvet CY, Yuan Y, Hammell AB, Drilon A, Solomon BJ. Repotrectinib in NTRK fusion-positive advanced solid tumors: a phase 1/2 trial. Nat Med. 2026 Feb;32(2):682-689. doi: 10.1038/s41591-025-04079-7. Epub 2026 Feb 4.

    PubMed 41639379

  • Ajani JA, D'Amico TA, Bentrem DJ, Corvera CU, Das P, Enzinger PC, Enzler T, Gerdes H, Gibson MK, Grierson P, Gupta G, Hofstetter WL, Ilson DH, Jalal S, Kim S, Kleinberg LR, Klempner S, Lacy J, Lee B, Licciardi F, Lloyd S, Ly QP, Matsukuma K, McNamara M, Merkow RP, Miller AM, Mukherjee S, Mulcahy MF, Perry KA, Pimiento JM, Reddi DM, Reznik S, Roses RE, Strong VE, Su S, Uboha N, Wainberg ZA, Willett CG, Woo Y, Yoon HH, McMillian NR, Stein M. Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology. J Natl Compr Canc Netw. 2025 May;23(5):169-191. doi: 10.6004/jnccn.2025.0022.

    PubMed 40341199

  • Drilon A, Camidge DR, Lin JJ, Kim SW, Solomon BJ, Dziadziuszko R, Besse B, Goto K, de Langen AJ, Wolf J, Lee KH, Popat S, Springfeld C, Nagasaka M, Felip E, Yang N, Velcheti V, Lu S, Kao S, Dooms C, Krebs MG, Yao W, Beg MS, Hu X, Moro-Sibilot D, Cheema P, Stopatschinskaja S, Mehta M, Trone D, Graber A, Sims G, Yuan Y, Cho BC; TRIDENT-1 Investigators. Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Jan 11;390(2):118-131. doi: 10.1056/NEJMoa2302299.

    PubMed 38197815

  • Yun MR, Kim DH, Kim SY, Joo HS, Lee YW, Choi HM, Park CW, Heo SG, Kang HN, Lee SS, Schoenfeld AJ, Drilon A, Kang SG, Shim HS, Hong MH, Cui JJ, Kim HR, Cho BC. Repotrectinib Exhibits Potent Antitumor Activity in Treatment-Naive and Solvent-Front-Mutant ROS1-Rearranged Non-Small Cell Lung Cancer. Clin Cancer Res. 2020 Jul 1;26(13):3287-3295. doi: 10.1158/1078-0432.CCR-19-2777. Epub 2020 Apr 8.

    PubMed 32269053

  • Drilon A, Ou SI, Cho BC, Kim DW, Lee J, Lin JJ, Zhu VW, Ahn MJ, Camidge DR, Nguyen J, Zhai D, Deng W, Huang Z, Rogers E, Liu J, Whitten J, Lim JK, Stopatschinskaja S, Hyman DM, Doebele RC, Cui JJ, Shaw AT. Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations. Cancer Discov. 2018 Oct;8(10):1227-1236. doi: 10.1158/2159-8290.CD-18-0484. Epub 2018 Aug 9.

    PubMed 30093503

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Oral repotrectinib (TPX-0005) in people with Locally Advanced Solid Tumors and Metastatic Solid Tumors, run by Turning Point Therapeutics, Inc. at 165 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 165 sites in United States, China, South Korea, Japan, France and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact BMS Clinical Trials Contact Center www.BMSClinicalTrials.com (855-907-3286, Clinical.Trials@bms.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicities (DLTs) (Phase 1) (time frame: Within 28 days of the first repotrectinib dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03093116, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.

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