A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)

February 5, 2024 updated by: Turning Point Therapeutics, Inc.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

500

Phase

  • Phase 2
  • Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: BMS Study Connect Contact Center www.BMSStudyConnect.com
  • Phone Number: 855-907-3286
  • Email: Clinical.Trials@bms.com

Study Contact Backup

  • Name: First line of the email MUST contain the NCT# and Site #.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Recruiting
        • Local Institution - 6102
        • Contact:
          • Site 6102
    • South Australia
      • Adelaide, South Australia, Australia, 5042
        • Recruiting
        • Local Institution - 6103
        • Contact:
          • Site 6103
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Recruiting
        • Local Institution - 6101
        • Contact:
          • Site 6101
  • Belgium
      • Antwerp, Belgium, 2650
        • Recruiting
        • Local Institution - 4802
        • Contact:
          • Site 4802
      • Leuven, Belgium, 3000
        • Recruiting
        • Local Institution - 4801
        • Contact:
          • Site 4801
  • Canada
      • Ontario, Canada, L6R 37R
        • Recruiting
        • Local Institution - 2203
        • Contact:
          • Site 2203
      • Ottawa, Canada, K1H 8L6
        • Recruiting
        • Local Institution - 2204
        • Contact:
          • Site 2204
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Recruiting
        • Local Institution - 2202
        • Contact:
          • Site 2202
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E7
        • Withdrawn
        • Local Institution - 2205
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Local Institution - 2201
        • Contact:
          • Site 2201
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Local Institution - 6503
        • Contact:
          • Site 6503
  • China
      • Changchun City, China, 000000
        • Recruiting
        • Jilin Cancer Hospital/Medical Oncology Department
        • Contact:
          • Ying Cheng, Site 6717
          • Phone Number: 8613943012851
      • Changsha, China, 00000
        • Recruiting
        • The Third Xiangya Hospital of Central South University/Department of Respiratory and Critical Care Medicine
        • Contact:
          • Jie Meng, Site 6734
      • Chengdu, China, 00000
        • Recruiting
        • West China Hospital Sichuan University/Lung cancer center
        • Contact:
          • Feng Luo, Site 6724
          • Phone Number: +8618980601766
      • Hangzhou, China, 310003
        • Recruiting
        • The First Affiliated Hospital - Zhejiang University School of Medicine
        • Contact:
          • Jianying Zhou, Site 6712
          • Phone Number: 8613505719970
      • Hefei, China, 230001
        • Recruiting
        • Local Institution - 6704
        • Contact:
          • Site 6704
      • Shanghai, China, 200030
        • Recruiting
        • Shanghai Chest Hospital
        • Contact:
          • Shun Lu, Site 6701
          • Phone Number: 8613601813062
      • Weifang City, China, 00000
        • Recruiting
        • Weifang People's Hospital/Medical Oncology Department
        • Contact:
          • Guohua Yu, Site 6727
      • Wuhan, China, 000000
        • Recruiting
        • Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology/Cancer Center Department
        • Contact:
          • Xiaorong Dong, Site 6710
          • Phone Number: 13986252286
      • Zhengzhou, China, 00000
        • Recruiting
        • Henan Cancer Hospital/The 1st pneumology department
        • Contact:
          • Xiufeng Hu, Site 6715
          • Phone Number: +8618339920984
    • Beijing
      • Beijing, Beijing, China, 100142
        • Recruiting
        • Beijing Cancer Hospital
        • Contact:
          • Jian Fang, Site 6703
          • Phone Number: 868613701224460
      • Beijing, Beijing, China, 100021
        • Completed
        • Local Institution - 6702
    • Chongqing
      • Daping, Chongqing, China, 00000
        • Recruiting
        • Daping Hospital, the Third Affiliated Hospital of Third Military Medical University /Cancer Center
        • Contact:
          • Yong He, Site 6736
          • Phone Number: 13908338998
    • Fujian
      • Fuzhou, Fujian, China, 000000
        • Completed
        • Local Institution - 6719
      • Xiamen, Fujian, China, 361003
        • Recruiting
        • The First Affiliated hospital of Xiamen University-oncology
        • Contact:
          • Jingxun Wu, Site 6708
    • Guangdong
      • Guangzhou, Guangdong, China, 510120
        • Recruiting
        • Guangdong Provincial People's Hospital
        • Contact:
          • Jinji Yang, Site 6747
      • Guangzhou, Guangdong, China, 510120
        • Recruiting
        • The First Affiliated Hospital of Guangzhou Medical University-Pneumology department
        • Contact:
          • Huaqiu Shi, Site 6733
      • Shenzhen, Guangdong, China, 518053
        • Recruiting
        • Local Institution - 6505
        • Contact:
          • Site 6505
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
        • Recruiting
        • The Affiliated Tumor Hospital of Harbin Medical University
        • Contact:
          • Yan Yu, Site 6722
          • Phone Number: 13904505825
    • Hong Kong
      • Shatin, Hong Kong, China, 999077
        • Recruiting
        • Local Institution - 6504
        • Contact:
          • Site 6504
    • Hunan
      • Changsha, Hunan, China, 410011
        • Completed
        • Local Institution - 6705
      • Changsha, Hunan, China, 410013
        • Recruiting
        • Hunan Cancer Hospital-thoracic oncology II
        • Contact:
          • Nong Yang, Site 6718
          • Phone Number: 13055193557
    • Jiangsu
      • Nanjing, Jiangsu, China, 210008
        • Recruiting
        • Nanjing Drum Tower Hospital
        • Contact:
          • Liyun Miao, Site 6748
      • Xuzhou City, Jiangsu, China, 00000
        • Recruiting
        • XuZhou Central Hospital/Oncology Department
        • Contact:
          • Xiang Wang, Site 6732
    • Jilin
      • Changchun, Jilin, China, 130021
        • Recruiting
        • Local Institution - 6714
        • Contact:
          • Site 6714
    • Liaoning
      • Shenyang, Liaoning, China, 110801
        • Recruiting
        • Local Institution - 6742
        • Contact:
          • Site 6742
    • Shan3xi
      • Xi'an, Shan3xi, China, 710038
        • Recruiting
        • Tangdu Hospital
        • Contact:
          • Haichuan Su, Site 6754
    • Shanxi
      • Taiyuan, Shanxi, China, 030032
        • Recruiting
        • Shanxi Bethune Hospital
        • Contact:
          • Junping Zhang, Site 6749
          • Phone Number: 13994204099
    • Sichuan
      • Chengdu City, Sichuan, China, 00000
        • Recruiting
        • Sichuan Cancer Hospital/Medical Oncology Department
        • Contact:
          • Wenxiu Yao, Site 6728
          • Phone Number: 18908178836
      • Chongqing, Sichuan, China, 400030
        • Recruiting
        • Local Institution - 6716
        • Contact:
          • Site 6716
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310016
        • Recruiting
        • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
        • Contact:
          • Kejing Ying, Site 6725
          • Phone Number: 8613588706900
      • Hangzhou, Zhejiang, China, 310022
        • Recruiting
        • Zhejiang Cancer Hospital-Oncology
        • Contact:
          • Yiping Zhang, Site 6721
  • Denmark
      • Copenhagen, Denmark, 2100
        • Recruiting
        • Local Institution - 4901
        • Contact:
          • Site 4901
  • France
      • Brest, France, 29200
        • Recruiting
        • Local Institution - 4207
        • Contact:
          • Site 4207
      • Dijon Cedex, France, 21079
        • Recruiting
        • Local Institution - 4204
        • Contact:
          • Site 4204
      • Grenoble Cedex 9, France, 38043
        • Recruiting
        • Local Institution - 4206
        • Contact:
          • Site 4206
      • Nice, France, 06189
        • Recruiting
        • Local Institution - 4205
        • Contact:
          • Site 4205
      • Poitiers, France, 86000
        • Recruiting
        • Local Institution - 4208
        • Contact:
          • Site 4208
      • St Mande, France, 94163
        • Recruiting
        • Local Institution - 4203
        • Contact:
          • Site 4203
      • Villejuif, France, 98405
        • Recruiting
        • Local Institution - 4202
        • Contact:
          • Site 4202
    • Bouches-du-Rhône
      • Marseille, Bouches-du-Rhône, France, 13005
        • Recruiting
        • Local Institution - 4201
        • Contact:
          • Site 4201
  • Germany
      • Berlin, Germany, 13125
        • Recruiting
        • Local Institution - 4704
        • Contact:
          • Site 4704
      • Dresden, Germany, 01307
        • Recruiting
        • Local Institution - 4703
        • Contact:
          • Site 4703
      • Heidelberg, Germany, 69120
        • Recruiting
        • Local Institution - 4702
        • Contact:
          • Site 4702
      • Koln, Germany, 50937
        • Recruiting
        • Local Institution - 4701
        • Contact:
          • Site 4701
  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Local Institution - 6502
        • Contact:
          • Site 6502
      • Hong Kong, Hong Kong
        • Recruiting
        • Local Institution - 6501
        • Contact:
          • Site 6501
  • Hungary
      • Budapest, Hungary, 1083
        • Recruiting
        • Local Institution - 5101
        • Contact:
          • Site 5101
      • Budapest, Hungary, 1121
        • Recruiting
        • Local Institution - 5103
        • Contact:
          • Site 5103
  • Italy
      • Milano, Italy, 20122
        • Recruiting
        • Local Institution - 4306
        • Contact:
          • Site 4306
      • Palermo, Italy, 90146
        • Withdrawn
        • Local Institution - 4307
      • Pordenone, Italy, 33081
        • Recruiting
        • Local Institution - 4303
        • Contact:
          • Site 4303
      • Reggio Emilia, Italy, 42123
        • Recruiting
        • Local Institution - 4305
        • Contact:
          • Site 4305
      • Roma, Italy, 144
        • Recruiting
        • Local Institution - 4308
        • Contact:
          • Site 4308
      • Terni, Italy, 05100
        • Recruiting
        • Local Institution - 4302
        • Contact:
          • Site 4302
    • MI
      • Milano, MI, Italy, 20133
        • Recruiting
        • Local Institution - 4301
        • Contact:
          • Site 4301
  • Japan
      • Kashiwa, Japan, 277-8577
        • Recruiting
        • National Cancer Center Hospital East
        • Contact:
          • Koichi Goto, Site 6601
          • Phone Number: 81471331111
      • Nagoya-shi, Japan, 466-8560
        • Recruiting
        • Local Institution - 6608
        • Contact:
          • Site 6608
      • Osaka, Japan, 5418567
        • Recruiting
        • Local Institution - 6602
        • Contact:
          • Site 6602
    • Ehime
      • Toon, Ehime, Japan, 791-0295
        • Recruiting
        • Local Institution - 6609
        • Contact:
          • Site 6609
    • Hokkaido
      • Sapporo-shi, Hokkaido, Japan, 0608648
        • Recruiting
        • Local Institution - 6607
        • Contact:
          • Site 6607
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 2418515
        • Recruiting
        • Local Institution - 6603
        • Contact:
          • Site 6603
    • Osaka
      • Osaka-shi, Osaka, Japan, 5340021
        • Recruiting
        • Local Institution - 6605
        • Contact:
          • Site 6605
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 1040045
        • Recruiting
        • Local Institution - 6604
        • Contact:
          • Site 6604
    • Tottori
      • Yonago, Tottori, Japan, 683-8504
        • Recruiting
        • Local Institution - 6606
        • Contact:
          • Site 6606
  • Korea, Democratic People's Republic of
      • Seoul, Korea, Democratic People's Republic of, 05505
        • Recruiting
        • Local Institution - 6305
        • Contact:
          • Site 6305
  • Korea, Republic of
      • Cheongju-si, Korea, Republic of, 28644
        • Recruiting
        • Local Institution - 6306
        • Contact:
          • Site 6306
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Local Institution - 6302
        • Contact:
          • Site 6302
      • Seoul, Korea, Republic of, 05030
        • Recruiting
        • Local Institution - 6307
        • Contact:
          • Site 6307
      • Seoul, Korea, Republic of, 06591
        • Recruiting
        • Local Institution - 6304
        • Contact:
          • Site 6304
    • Jeonnam
      • Hwasun-eup, Hwasun-gun, Jeonnam, Korea, Republic of, 519-763
        • Recruiting
        • Local Institution - 6308
        • Contact:
          • Site 6308
    • Seoul-teukbyeolsi [Seoul]
      • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 03080
        • Recruiting
        • Local Institution - 6301
        • Contact:
          • Site 6301
      • Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of, 06351
        • Recruiting
        • Local Institution - 6303
        • Contact:
          • Site 6303
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Recruiting
        • Local Institution - 4502
        • Contact:
          • Site 4502
      • Groningen, Netherlands, 9713 GZ
        • Recruiting
        • Local Institution - 4501
        • Contact:
          • Site 4501
  • Poland
      • Gdańsk, Poland, 80-214
        • Recruiting
        • Local Institution - 4601
        • Contact:
          • Site 4601
      • Lublin, Poland, 20-609
        • Recruiting
        • Local Institution - 4604
        • Contact:
          • Site 4604
      • Poznań, Poland, 60-693
        • Recruiting
        • Local Institution - 4605
        • Contact:
          • Site 4605
      • Szczecin, Poland, 70-784
        • Recruiting
        • Local Institution - 4603
        • Contact:
          • Site 4603
      • Warszawa, Poland, 02-781
        • Recruiting
        • Local Institution - 4602
        • Contact:
          • Site 4602
  • Singapore
      • Singapore, Singapore, 119074
        • Recruiting
        • Local Institution - 6401
        • Contact:
          • Site 6401
      • Singapore, Singapore, 169610
        • Recruiting
        • Local Institution - 6402
        • Contact:
          • Site 6402
  • Spain
      • Barcelona, Spain, 08028
        • Recruiting
        • Local Institution - 4102
        • Contact:
          • Site 4102
      • Barcelona, Spain, 8035
        • Recruiting
        • Local Institution - 4101
        • Contact:
          • Site 4101
      • Madrid, Spain, 28033
        • Recruiting
        • Local Institution - 4106
        • Contact:
          • Site 4106
      • Madrid, Spain, 28040
        • Recruiting
        • Local Institution - 4104
        • Contact:
          • Site 4104
      • Madrid, Spain, 28041
        • Recruiting
        • Local Institution - 4103
        • Contact:
          • Site 4103
      • Madrid, Spain, 28050
        • Recruiting
        • Local Institution - 4105
        • Contact:
          • Site 4105
      • Pamplona, Spain, 31008
        • Recruiting
        • Local Institution - 4108
        • Contact:
          • Site 4108
      • Valencia, Spain, 46009
        • Recruiting
        • Local Institution - 4107
        • Contact:
          • Site 4107
  • Taiwan
      • Taiepi, Taiwan, 100
        • Recruiting
        • Local Institution - 6201
        • Contact:
          • Site 6201
      • Tainan, Taiwan, 704
        • Recruiting
        • Local Institution - 6203
        • Contact:
          • Site 6203
      • Taipei, Taiwan, 10449
        • Recruiting
        • Local Institution - 6202
        • Contact:
          • Site 6202
  • United Kingdom
      • London, United Kingdom, SW3 6JJ
        • Recruiting
        • Local Institution - 4401
        • Contact:
          • Site 4401
      • London, United Kingdom, W12 OHS
        • Recruiting
        • Local Institution - 4402
        • Contact:
          • Site 4402
      • London, United Kingdom, W1G 6AD
        • Recruiting
        • Local Institution - 4404
        • Contact:
          • Site 4404
      • Manchester, United Kingdom, M20 4BX
        • Recruiting
        • Local Institution - 4403
        • Contact:
          • Site 4403
      • Sutton, United Kingdom, SM2 5PT
        • Recruiting
        • Local Institution - 4405
        • Contact:
          • Site 4405
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
          • Nishan Tchekmedyian, Site 2129
          • Phone Number: 562-590-0345
      • Glendale, California, United States, 91206
        • Recruiting
        • Adventist Health Glendale
        • Contact:
          • Mihran Shirinian, Site 2120
          • Phone Number: 818-409-6687
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Health
        • Contact:
          • Lyudmila Bazhenova, Site 2114
          • Phone Number: 866-773-2703
      • Long Beach, California, United States, 90813
        • Recruiting
        • Pacific Shores Medical Group
        • Contact:
          • Nishan Tchekmedyian, Site 2121
          • Phone Number: 562-590-0345
      • Orange, California, United States, 92868
        • Recruiting
        • UC Irvine Medical Center
        • Contact:
          • Misako Nagasaka, Site 2101
          • Phone Number: 714-456-5153
      • Santa Rosa, California, United States, 95403
        • Recruiting
        • St Joseph Heritage Healthcare
        • Contact:
          • Ian Anderson, Site 2126
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Denver
        • Contact:
          • Ross Camidge, Site 2103
          • Phone Number: 720-848-0449
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University Medical Center - Lombardi Comprehensive Cancer Center
        • Contact:
          • Stephen Liu, Site 2106
          • Phone Number: 202-444-2223
      • Washington, District of Columbia, United States, 20016
        • Recruiting
        • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
        • Contact:
          • Benjamin Levy, Site 2110
          • Phone Number: 347-324-6573
    • Florida
      • Hollywood, Florida, United States, 33021
        • Recruiting
        • Memorial Healthcare System
        • Contact:
          • Luis Raez, Site 2128
          • Phone Number: 954-265-4325
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Contact:
          • Benjamin Creelan, Site 2113
          • Phone Number: 813-745-6895
    • Georgia
      • Athens, Georgia, United States, 30607
        • Recruiting
        • University Cancer and Blood Center
        • Contact:
          • PETROS NIKOLINAKOS, Site 2139
          • Phone Number: 706-353-2990
      • Columbus, Georgia, United States, 31904
        • Recruiting
        • Colombus Regional Research Institute
        • Contact:
          • Andrew Pippas, Site 2134
          • Phone Number: 706-660-6449
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago
        • Contact:
          • Christine Bestvina, Site 2125
          • Phone Number: 773-702-4400
      • Peoria, Illinois, United States, 61615
        • Recruiting
        • Illinois Cancer Care
        • Contact:
          • Greg Gerstner, Site 2142
    • Maryland
      • Baltimore, Maryland, United States, 21210
        • Recruiting
        • University of Maryland Medical Center
        • Contact:
          • Katherine Scilla, Site 2133
          • Phone Number: 410-328-6373
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana Farber Cancer Institute.
        • Contact:
          • Mark Awad, Site 2131
          • Phone Number: 617-632-3468
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital,
        • Contact:
          • Jessica Lin, Site 2104
          • Phone Number: 617-724-4000
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Contact:
          • Angel Qin, Site 2105
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Institute
        • Contact:
          • Dipesh Uprety, Site 2111
          • Phone Number: 215-285-2261
      • Detroit, Michigan, United States, 48202-2608
        • Recruiting
        • Henry Ford Transplant Institute
        • Contact:
          • Shirish Gadgeel, Site 2140
          • Phone Number: 313-399-0508
    • Minnesota
      • Saint Paul, Minnesota, United States, 55101
        • Recruiting
        • Regions Hospital - Cancer Care Center
        • Contact:
          • Arkadiusz Dudek, Site 2132
          • Phone Number: 31299615816512543321
    • Missouri
      • Bolivar, Missouri, United States, 65613
        • Recruiting
        • Central Care Cancer Center
        • Contact:
          • Leonid Shunyakov, Site 2147
          • Phone Number: 417-326-7200
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University Infusion Center Pharmacy
        • Contact:
          • Brian Van Tine, Site 2115
          • Phone Number: 314-747-3096
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
        • Contact:
          • Scott Moerdler, Site 2122
          • Phone Number: 000-000-0000
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Alexander Drilon, Site 2102
          • Phone Number: 646-888-4206
      • New York, New York, United States, 10016
        • Recruiting
        • Laura & Isaac Perlmutter Cancer Center
        • Contact:
          • Vamsidhar Velcheti, Site 2117
          • Phone Number: 216-903-4153
    • North Carolina
      • Goldsboro, North Carolina, United States, 27534
        • Recruiting
        • Southeastern Medical Oncology Center
        • Contact:
          • Samer Kasbari, Site 2144
          • Phone Number: 919-580-0000
    • Ohio
      • Canton, Ohio, United States, 44718
        • Recruiting
        • Gabrail Cancer Center
        • Contact:
          • Nashat Gabrail, Site 2112
          • Phone Number: 330-417-8231
      • Cincinnati, Ohio, United States, 45220
        • Recruiting
        • TriHealth Cancer Institute
        • Contact:
          • Faisal Adhami, MD, Site 2143
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic Main Campus
        • Contact:
          • Pete Anderson, Site 2109
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Wexner Medical Center
        • Contact:
          • Dwight Owen, Site 2123
          • Phone Number: 614-293-6401
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Recruiting
        • Fox Chase Cancer Center
        • Contact:
          • Jessica Bauman, Site 2108
          • Phone Number: 215-728-5673
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • Recruiting
        • Baptist Memorial Hospital Baptist Cancer Center
        • Contact:
          • Philip Lammers, Site 2148
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern Medical Center
        • Contact:
          • Syed Kazmi, Site 2130
          • Phone Number: 214-648-5368
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
          • Yasir Elamin, Site 2138
      • Houston, Texas, United States, 77030
        • Recruiting
        • Oncology Consultants, P.A.
        • Contact:
          • Julio Peguero, Site 2127
          • Phone Number: 713-600-0913
      • Kingwood, Texas, United States, 77339
        • Recruiting
        • Lumi Research
        • Contact:
          • Saleha Sajid, Site 2146
          • Phone Number: 832-553-3661
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists, PC
        • Contact:
          • Alexander Spira, Site 2137
          • Phone Number: 703-280-5390
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • University of Washington-Seattle Cancer Care Alliance
        • Contact:
          • Christina Baik, Site 2107
    • Wisconsin
      • Appleton, Wisconsin, United States, 54911
        • Recruiting
        • ThedaCare
        • Contact:
          • Matthias Weiss, Site 2145

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Repotrectinib (TPX-0005)

Phase 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
Drug: Oral repotrectinib (TPX-0005)
Oral repotrectinib (TPX-0005) capsules.
Other Names:
  • repotrectinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose limiting toxicities (DLTs) (Phase 1)
Time Frame: Within 28 days of the first repotrectinib dose
Define the dose limiting toxicities (DLTs) (Phase 1)
Within 28 days of the first repotrectinib dose
Recommended Phase 2 Dose (RP2D) (Phase 1)
Time Frame: Within 28 days of the last patient dosed in escalation
To determine the RP2D (Phase 1)
Within 28 days of the last patient dosed in escalation
Overall Response Rate (ORR) Phase 2
Time Frame: Two to three years after first dose of repotrectinib dose
To determine the confirmed ORR of repotrectinib (TPX-0005) as assessed by Blinded Independent Central Review (Phase 2)
Two to three years after first dose of repotrectinib dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum plasma concentration (CMAX) of repotrectinib (TPX-0005) (Phase 1)
Time Frame: Up to 72 hours post dose
To determine the maximum plasma concentration (CMAX) of repotrectinib (TPX-0005)
Up to 72 hours post dose
Area under the plasma concentration time curve (AUC) of repotrectinib (TPX-0005) (Phase 1)
Time Frame: Up to 72 hours post dose
To determine the area under the plasma concentration time curve (AUC) of repotrectinib
Up to 72 hours post dose
Area under the plasma concentration time curve (AUC) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1)
Time Frame: Up to 72 hours post dose
To determine the area under the plasma concentration time curve (AUC) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1)
Up to 72 hours post dose
Maximum plasma concentration (CMAX) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1)
Time Frame: Up to 72 hours post dose
To determine the maximum plasma concentration (CMAX) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1)
Up to 72 hours post dose
Area under the plasma concentration time curve (AUC) of midazolam(TPX-0005) (Phase 1)
Time Frame: Up to 24 hours post dose
To determine the area under the plasma concentration time curve (AUC) of midazolam(TPX-0005) (Phase 1)
Up to 24 hours post dose
Maximum plasma concentration (CMAX) of midazolam(TPX-0005) (Phase 1)
Time Frame: Up to 24 hours post dose
To determine the maximum plasma concentration (CMAX) of midazolam(TPX-0005) (Phase 1)
Up to 24 hours post dose
Plasma concentration of repotrectinib following administration at RP2D (Phase 2)
Time Frame: Pre dose and 4 hours post dose
To evaluate the plasma concentration of repotrectinib following administration at RP2D (Phase 2)
Pre dose and 4 hours post dose
Preliminary objective response rate (ORR) (Phase 1)
Time Frame: Approximately three years
To determine the preliminary objective response rate (ORR) by Blinded Independent Central Review (BICR) (Phase 1)
Approximately three years
Duration of response (DOR) (Phase 2)
Time Frame: Approximately three years
To determine the DOR of repotrectinib (TPX-0005) (Phase 2)
Approximately three years
Clinical benefit rate (CBR) (Phase 2)
Time Frame: Approximately three years
To determine the CBR of repotrectinib (TPX-0005) (Phase 2)
Approximately three years
Progression free survival (PFS) (Phase 2)
Time Frame: Approximately three years
To determine the PFS (Phase 2)
Approximately three years
Overall survival (OS) (Phase 2)
Time Frame: Approximately three years
To determine the OS (Phase 2)
Approximately three years
Intracranial objective response rate (Phase 2)
Time Frame: Approximately three years
To determine the intracranial objective response rate (Phase 2)
Approximately three years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Turning Point Therapeutics, Inc.

Collaborators

Zai Lab (Shanghai) Co., Ltd.

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 7, 2017

Primary Completion (Estimated)

February 29, 2028

Study Completion (Estimated)

February 29, 2028

Study Registration Dates

First Submitted

March 6, 2017

First Submitted That Met QC Criteria

March 21, 2017

First Posted (Actual)

March 28, 2017

Study Record Updates

Last Update Posted (Estimated)

February 7, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA127-1024 (Other Identifier: BMS Protocol ID)
  • TPX-0005-01 (Other Identifier: Turning Point Therapeutics Protocol ID)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There are no plans to share individual participant data with other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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