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.

Antineoplastic Agents

Micronutrients

Hematinics

Vitamins

Carboplatin

Pemetrexed

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Pemetrexed (500 mg/m2),carboplatin (area under the concentration-time curve of 6 mg/mL x min) once every 21 days X 4 cycles, pemetrexed maintenance and placebo starting at Day 84

Pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve of 6 mg/mL x min) x 4 cycles, one course of demcizumab 5mg/kg, maintenance pemetrexed + placebo starting on Day 84

Pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve of 6 mg/mL x min) x 4 cycles, maintenance pemetrexed starting on Day 84. 2 courses of demcizumab 5 mg/kg

demcizumab

A randomized, double-blind, 3-arm (1:1:1) study in subjects with first-line Stage IV non-squamous NSCLC. The purpose is to test the efficacy and safety of demcizumab, when given in combination with carboplatin and pemetrexed compared to placebo. The administration of carboplatin and pemetrexed is a standard treatment for patients with non-squamous non-small cell lung cancer.

Patients will be enrolled at centers in North America, Western Europe, Australia and New Zealand. Up to 28 days (4 weeks) prior to treatment.

If enrolled in the study, you will receive intravenous (in the vein) infusions of demcizumab (or placebo), carboplatin, and pemetrexed administered on the same day, every 21 days for 4 cycles, or until it has been shown that your cancer has gotten worse. If your physician decides to delay treatment with one of the agents due to side effects, the other agents may still be administered as scheduled. After 4 cycles, if you have stable or improved disease, you will continue to receive pemetrexed once every 21 days as maintenance therapy. After 8 cycles, if you have stable or improved disease, you may receive demcizumab (or placebo), every 21 days for 4 more cycles.

You will undergo assessments every 6 weeks to determine the status of your disease.

A Study of Carboplatin, Pemetrexed Plus Placebo vs Carboplatin, Pemetrexed Plus 1 or 2 Truncated Courses of Demcizumab in Subjects With Non-Squamous Non-Small Cell Lung Cancer

A 2-Arm Phase 2 Double-Blind Randomized Study of Carboplatin, Pemetrexed Plus Placebo Versus Carboplatin, Pemetrexed Plus Truncated Demcizumab as First-Line Treatment in Subjects With Stage IV Non-Squamous Non-Small Cell Lung Cancer

Investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response rate (unconfirmed) in placebo/placebo arm to demcizumab/placebo arm and demcizumab/demcizumab arm combined in subjects with first-line stage IV non-small cell lung cancer (NSCLC). Response rate was based on Investigator-assessed best-overall-response (BOR) and was defined as the best unconfirmed response determined by RECIST version 1.1 recorded from the start of the treatment until disease progression in the following order of importance: CR, PR , SD, progressive disease (PD), not evaluable, or missing.

Celgene Corporation

OncoMed Pharmaceuticals, Inc.

All reported adverse events were mapped to standard MedDRA coding terms, grouped by system organ class and preferred term and tabulated by treatment arm.

Placebo plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles)

Placebo/Placebo Arm (Arm 1)

Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles)

Demcizumab/Placebo Arm (Arm 2)

Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), demcizumab plus pemetrexed (4 cycles)

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.
A Study of Carboplatin, Pemetrexed Plus Placebo vs Carboplatin, Pemetrexed Plus 1 or 2 Truncated Courses of Demcizumab in Subjects With Non-Squamous Non-Small Cell Lung Cancer	NCT02259582	Nonsquamous Non...	Pemetrexed Carboplatin demcizumab	21 Years -	Mereo BioPharma
A Clinica Study of Pyrotinib in Patients of Advanced Non-Small Cell Lung Cancer With HER2 Mutation	NCT02834936	Non Small Cell ...	pyrotinib	18 Years - 75 Years	Jiangsu HengRui Medicine Co., Ltd.
Phase 1/2 Study of Vascular Disrupting Agent NPI-2358 + Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer	NCT00630110	Cancer	docetaxel NPI-2358 + doce...	18 Years -	Nereus Pharmaceuticals, Inc.
Osimertinib or Docetaxel-bevacizumab as Third-line Treatment in EGFR T790M Mutated Non-Small Cell Lung Cancer	NCT02959749	Progression Fre...	Osimertinib docetaxel, beva...	18 Years - 80 Years	Qingdao Central Hospital
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.
A Clinica Study of Pyrotinib in Patients of Advanced Non-Small Cell Lung Cancer With HER2 Mutation	NCT02834936	Non Small Cell ...	pyrotinib	18 Years - 75 Years	Jiangsu HengRui Medicine Co., Ltd.
Osimertinib or Docetaxel-bevacizumab as Third-line Treatment in EGFR T790M Mutated Non-Small Cell Lung Cancer	NCT02959749	Progression Fre...	Osimertinib docetaxel, beva...	18 Years - 80 Years	Qingdao Central Hospital
Safety Study of a Liposomal Docetaxel Formulation in Patients With Solid Tumors Who Have Failed Previous Therapies	NCT01041235	Solid Tumor Breast Cancer Ovarian Cancer Pancreatic Canc... Non-Small Cell ...	ATI-1123 (activ...	18 Years -	Azaya Therapeutics, Inc.
Phase 1/2 Study of Vascular Disrupting Agent NPI-2358 + Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer	NCT00630110	Cancer	docetaxel NPI-2358 + doce...	18 Years -	Nereus Pharmaceuticals, Inc.
SELINE: Second-Line Iressa Phase IV Study in NSCLC Patients	NCT00608868	Non Small Cell ...	Gefitinib	19 Years - 80 Years	AstraZeneca

Spots Global Cancer Trial Database for non small cell lung