Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Adenocarcinoma

Colonic Neoplasms

Colonic Diseases

Lung Diseases

Thyroid Neoplasms

Thyroid Diseases

Gastrointestinal Diseases

Neuroendocrine Tumors

Head and Neck Neoplasms

Gastrointestinal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Carcinoma, Neuroendocrine

Sarcoma

Neoplasms, Germ Cell and Embryonal

Endocrine Gland Neoplasms

Respiratory Tract Diseases

Thoracic Neoplasms

Digestive System Neoplasms

Respiratory Tract Neoplasms

Bronchial Neoplasms

Carcinoma, Bronchogenic

Endocrine System Diseases

Neoplasms by Histologic Type

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neuroendocrine Tumor

Soft Tissue Sarcoma

Neuroepithelioma

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Herbal and Botanical

Midazolam

Cola

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

Oral repotrectinib (TPX-0005)

BMS Study Connect Contact Center www.BMSStudyConnect.com

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

Nishan Tchekmedyian, Site 2129

Mihran Shirinian, Site 2120

Lyudmila Bazhenova, Site 2114

Nishan Tchekmedyian, Site 2121

Misako Nagasaka, Site 2101

Ian Anderson, Site 2126

Ross Camidge, Site 2103

Stephen Liu, Site 2106

Benjamin Levy, Site 2110

Luis Raez, Site 2128

Benjamin Creelan, Site 2113

PETROS NIKOLINAKOS, Site 2139

Andrew Pippas, Site 2134

Christine Bestvina, Site 2125

Greg Gerstner, Site 2142

Katherine Scilla, Site 2133

Jessica Lin, Site 2104

Mark Awad, Site 2131

Angel Qin, Site 2105

Dipesh Uprety, Site 2111

Shirish Gadgeel, Site 2140

Arkadiusz Dudek, Site 2132

Leonid Shunyakov, Site 2147

Brian Van Tine, Site 2115

Scott Moerdler, Site 2122

Vamsidhar Velcheti, Site 2117

Alexander Drilon, Site 2102

Samer Kasbari, Site 2144

Nashat Gabrail, Site 2112

Faisal Adhami, MD, Site 2143

Pete Anderson, Site 2109

Dwight Owen, Site 2123

Jessica Bauman, Site 2108

Philip Lammers, Site 2148

Syed Kazmi, Site 2130

Yasir Elamin, Site 2138

Julio Peguero, Site 2127

Saleha Sajid, Site 2146

Alexander Spira, Site 2137

Christina Baik, Site 2107

Matthias Weiss, Site 2145

Site 6102

Site 6103

Site 6101

Site 4802

Site 4801

Site 2202

Site 2201

Site 6503

Site 2203

Site 2204

Jian Fang, Site 6703

Yong He, Site 6736

Jingxun Wu, Site 6708

Jinji Yang, Site 6747

Huaqiu Shi, Site 6733

Site 6505

Yan Yu, Site 6722

Site 6504

Nong Yang, Site 6718

Liyun Miao, Site 6748

Xiang Wang, Site 6732

Site 6714

Site 6742

Haichuan Su, Site 6754

Junping Zhang, Site 6749

Wenxiu Yao, Site 6728

Site 6716

Kejing Ying, Site 6725

Yiping Zhang, Site 6721

Meili Sun, Site 6720

Ying Cheng, Site 6717

Jie Meng, Site 6734

Feng Luo, Site 6724

Jianying Zhou, Site 6712

Site 6704

Liyan Jiang, Site 6709

Shun Lu, Site 6701

Guohua Yu, Site 6727

Xiaorong Dong, Site 6710

Xiufeng Hu, Site 6715

Site 4901

Site 4201

Site 4207

Site 4204

Site 4206

Site 4205

Site 4208

Site 4203

Site 4202

Site 4704

Site 4703

Site 4702

Site 4701

Site 6502

Site 6501

Bristol-Myers Squibb

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.

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.

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

To determine the intracranial objective response rate (Phase 2)

Zai Lab (Shanghai) Co., Ltd.

Turning Point Therapeutics, Inc.

Symptoms and General Pathology

Neoplasm Metastasis

Colorectal Neoplasms

Neoplasms, Second Primary

Rectal Diseases

Neoplastic Processes

Surgical resection of the primary tumour followed by chemotherapy +/- targeted therapy regime.

Surgical resection of the colon tumour, R0. No surgical intervention on metastasis.

surgery of the primary tumour

Chemotherapy with or without biological drugs.

chemotherapy

Iuliia Alimova, MD

Currently, the question remains whether palliative primary tumor resection could improve overall survival of minimally symptomatic patients with colorectal cancer and synchronous unresectable metastases. The aim of this study is to determine if there is an improvement in overall survival of palliative primary tumor resection followed by chemotherapy in minimally symptomatic patients with colorectal cancer and synchronous unresectable metastases compared to those of upfront chemotherapy/radiotherapy alone.

The present study is a single-center retrospective observational cohort study with a propensity score matching. Between 2016 and 2022 from our institutional database minimally symptomatic patients with colorectal cancer and synchronous unresectable metastases will be selected. Patients will be divided into two groups:

1. Surgical resection of the primary tumour before to systemic therapy
2. Systemic therapy without previous resection of the primary tumour. Propensity score matching (PSM) will be performed, to minimize the selection bias by adjusting variables that may affect the survival of patients. Categorical variables will be compared using the chi-square test or Fisher's exact test. Continuous variables will be compared using the Student's t-test or Mann-Whitney U test. Survival rate will be determined by using Kaplan-Meier analysis with a log-rank test. Univariate and multivariate analyses for survival will be conducted using Cox proportional hazard models. Statistical results will be considered significant at p values less than 0.05.

Palliative Primary Tumor Resection in Minimally Symptomatic Patients With Colorectal Cancer and Synchronous Unresectable Metastases

Palliative Primary Tumor Resection in Minimally Symptomatic Patients With Colorectal Cancer and Synchronous Unresectable Metastases Versus Chemotherapy Alone

PFS is defined as the time interval between the date of diagnosis and the first date of progression of the metastatic disease or death in both treatment arms.

State Scientific Centre of Coloproctology, Russian Federation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements	NCT03093116	Locally Advance... Metastatic Soli...	Oral repotrecti...	12 Years -	Turning Point Therapeutics, Inc.
Palliative Primary Tumor Resection in Minimally Symptomatic Patients With Colorectal Cancer and Synchronous Unresectable Metastases	NCT05322486	Colorectal Neop... Intestinal Neop... Gastrointestina... Digestive Syste... Neoplasms by Si... Neoplasms Neoplasms, Seco... Neoplasm Metast... Digestive Syste... Gastrointestina... Colonic Disease Intestinal Dise... Rectal Diseases	surgery of the ... chemotherapy	18 Years -	State Scientific Centre of Coloproctology, Russian Federation
Palliative Primary Tumor Resection in Minimally Symptomatic Patients With Colorectal Cancer and Synchronous Unresectable Metastases	NCT05322486	Colorectal Neop... Intestinal Neop... Gastrointestina... Digestive Syste... Neoplasms by Si... Neoplasms Neoplasms, Seco... Neoplasm Metast... Digestive Syste... Gastrointestina... Colonic Disease Intestinal Dise... Rectal Diseases	surgery of the ... chemotherapy	18 Years -	State Scientific Centre of Coloproctology, Russian Federation
A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements	NCT03093116	Locally Advance... Metastatic Soli...	Oral repotrecti...	12 Years -	Turning Point Therapeutics, Inc.

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