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| ID | Type | Description | Link |
|---|---|---|---|
| CA127-1025 | Other Identifier | BMS Protocol ID | |
| TPX-0005-13 | Other Identifier | Turning Point Therapeutics Protocol ID |
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Inability to achieve and optimize a dose that could provide a positive benefit risk profile
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A Phase 1b/2 Study of Repotrectinib in Combination with Other Anticancer Therapies for the Treatment of Subjects with KRAS-Mutant Advanced Solid Tumors (TRIDENT-2)
Phase 1 Dose Escalation: To evaluate tolerability of repotrectinib at increasing dose levels in combination with other anticancer therapies for the treatment of subjects with locally advanced or metastatic KRAS-mutant solid tumors
Phase 2 Efficacy Evaluation: Investigate the anti-tumor efficacy and safety of repotrectinib in combination with other anticancer therapies for the treatment of patients with locally advanced or metastatic KRAS-mutant solid tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TPX-0005 + Trametinib | Experimental | TPX-0005 + Trametinib Dose Escalation and Dose Expansion Dose escalation: KRAS G12D mutant advanced solid tumors. Dose expansion: KRAS G12D locally advanced or metastatic NSCLC |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TPX-0005 | Drug | Oral TPX-0005 capsules |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities | Number of participants with first cycle DLTs to determine Mean Tolderable Dose (MTD) and/or RP2D. A DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications that meets the criteria defined in each subprotocol. The MTD is defined as the highest dose level of repotrectinib given in combination with other anticancer therapy observed to cause a DLT in fewer than 33% of the treated subjects in the first treatment cycle (i.e., Cycle 1). | From initial dose to end of first cycle of treatment, approximately 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) Assessed the Investigator Using RECIST v1.1. | The ORR will be defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR). A confirmed response is a response that persists on a repeat imaging performed at least 4 weeks after initial documentation of response. Participants with a confirmed objective response (CR or PR) will be referred to as responders. Radiographic confirmation of objective tumor response (CR or PR) or disease progression will be based on RECIST v1.1. The ORR will be reported as the percentage of responders by RECIST v1.1 along with the corresponding two-sided 95% Clopper-Pearson exact CI. Complete Response (CR) = Disappearance of all target lesions Partial Response (PR) = >=30% decrease in the sum diameters of target lesions. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Local Institution - 2101 | California City | California | 90033 | United States | ||
| Local Institution - 2109 |
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| Label | URL |
|---|---|
| BMS Clinical Trial Information | View source |
| BMS Clinical Trial Patient Recruiting | View source |
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9 participants enrolled and treated in phase 1. No participants enrolled in phase 2.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Level 1 | Repotrectinib 120 mg QD, Trametinib 2 mg QD |
| FG001 | Dose Level 2 | Repotrectinib 120 mg QD, Trametinib 1.0 mg QD |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 4, 2022 |
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| Trametinib | Drug | Oral trametinib tablets |
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| From screening to end of treatment approximately 10 months |
| Cmax of Repotrectinib | Cmax is defined as maximum plasma concentration of the drug. | At Cycle 1 Day 1 and Cycle 1 Day 22 |
| Tmax of Repotrecitinib | Tmax is defined is the time to maximum plasma concentration | At Cycle 1 Day 1 and Cycle 1 Day 22 |
| AUC 0-24 of Repotrecitinib | Area under the plasma concentration time-curve. AUC from time 0 to 24 hours after dose. | At Cycle 1 Day 1 and Cycle 1 Day 22 |
| Cmax of Trametinib | Cmax is defined as maximum plasma concentration of the drug. | At Cycle 1 Day 1 and Cycle 1 Day 22 |
| Tmax of Trametinib | Tmax is defined is the time to maximum plasma concentration | At Cycle 1 Day 1 and Cycle 1 Day 22 |
| AUC 0-24 of Trametinib | Area under the plasma concentration time-curve. AUC from time 0 to 24 hours after dose. | At Cycle 1 Day 1 and Cycle 1 Day 22 |
| California City |
| California |
| 92663 |
| United States |
| Local Institution - 2106 | Denver | Colorado | 80218 | United States |
| Local Institution - 2108 | Nashville | Tennessee | 37203 | United States |
| Local Institution - 2107 | Houston | Texas | 77030 | United States |
| Local Institution - 2102 | Virginia Beach | Virginia | 22031 | United States |
| FG002 | Dose Level -2a | Repotrectinib 160 mg QD, Trametinib 1.0 mg QD |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Level 1 | Repotrectinib 120 mg QD, Trametinib 2 mg QD |
| BG001 | Dose Level 2 | Repotrectinib 120 mg QD, Trametinib 1.0 mg QD |
| BG002 | Dose Level -2a | Repotrectinib 160 mg QD, Trametinib 1.0 mg QD |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose Limiting Toxicities | Number of participants with first cycle DLTs to determine Mean Tolderable Dose (MTD) and/or RP2D. A DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications that meets the criteria defined in each subprotocol. The MTD is defined as the highest dose level of repotrectinib given in combination with other anticancer therapy observed to cause a DLT in fewer than 33% of the treated subjects in the first treatment cycle (i.e., Cycle 1). | All treated participants | Posted | Count of Participants | Participants | From initial dose to end of first cycle of treatment, approximately 28 days |
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| Secondary | Overall Response Rate (ORR) Assessed the Investigator Using RECIST v1.1. | The ORR will be defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR). A confirmed response is a response that persists on a repeat imaging performed at least 4 weeks after initial documentation of response. Participants with a confirmed objective response (CR or PR) will be referred to as responders. Radiographic confirmation of objective tumor response (CR or PR) or disease progression will be based on RECIST v1.1. The ORR will be reported as the percentage of responders by RECIST v1.1 along with the corresponding two-sided 95% Clopper-Pearson exact CI. Complete Response (CR) = Disappearance of all target lesions Partial Response (PR) = >=30% decrease in the sum diameters of target lesions. | Efficacy Evaluable Set - all participants who (1) received at least one dose of study treatment with repotrectinib; (2) KRAS mutation determined by a qPCR or NGS test performed in a CLIA laboratory or equivalently accredited diagnostic lab; (3) have a baseline tumor assessment with measurable disease and have at least 1 on-study tumor assessment per RECIST v1.1; and (4) have no major protocol violations that could affect efficacy. (Dose Level 1 and -2a did not meet efficacy evaluable criteria) | Posted | Number | 95% Confidence Interval | Percentage of Participants | From screening to end of treatment approximately 10 months |
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| Secondary | Cmax of Repotrectinib | Cmax is defined as maximum plasma concentration of the drug. | All Treated Participants with evaluable pharmacokinetic measurements. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | At Cycle 1 Day 1 and Cycle 1 Day 22 |
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| Secondary | Tmax of Repotrecitinib | Tmax is defined is the time to maximum plasma concentration | All Treated Participants with evaluable pharmacokinetic measurements. | Posted | Median | Full Range | hours (h) | At Cycle 1 Day 1 and Cycle 1 Day 22 |
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| Secondary | AUC 0-24 of Repotrecitinib | Area under the plasma concentration time-curve. AUC from time 0 to 24 hours after dose. | All Treated Participants with evaluable pharmacokinetic measurements. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | At Cycle 1 Day 1 and Cycle 1 Day 22 |
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| Secondary | Cmax of Trametinib | Cmax is defined as maximum plasma concentration of the drug. | All Treated Participants with evaluable pharmacokinetic measurements. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | At Cycle 1 Day 1 and Cycle 1 Day 22 |
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| Secondary | Tmax of Trametinib | Tmax is defined is the time to maximum plasma concentration | All Treated Participants with evaluable pharmacokinetic measurements. | Posted | Median | Full Range | hours (h) | At Cycle 1 Day 1 and Cycle 1 Day 22 |
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| Secondary | AUC 0-24 of Trametinib | Area under the plasma concentration time-curve. AUC from time 0 to 24 hours after dose. | All Treated Participants with evaluable pharmacokinetic measurements. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | At Cycle 1 Day 1 and Cycle 1 Day 22 |
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From first dose to 28 days after last dose, approximately 9.5 months
The number at Risk for All-Cause Mortality represents all Randomized Participants.
The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Level 1 | Repotrectinib 120 mg QD, Trametinib 2 mg QD | 2 | 2 | 0 | 2 | 2 | 2 |
| EG001 | Dose Level 2 | Repotrectinib 120 mg QD, Trametinib 1.0 mg QD | 2 | 5 | 1 | 5 | 5 | 5 |
| EG002 | Dose Level -2a | Repotrectinib 160 mg QD, Trametinib 1.0 mg QD | 1 | 2 | 2 | 2 | 2 | 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | 24.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | 24.1 | Systematic Assessment |
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| Asthenia | General disorders | 24.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 24.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 24.1 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | 24.1 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | 24.1 | Systematic Assessment |
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| Periorbital oedema | Eye disorders | 24.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | 24.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | 24.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | 24.1 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | 24.1 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | 24.1 | Systematic Assessment |
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| Haematochezia | Gastrointestinal disorders | 24.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | 24.1 | Systematic Assessment |
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| Paraesthesia oral | Gastrointestinal disorders | 24.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | 24.1 | Systematic Assessment |
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| Asthenia | General disorders | 24.1 | Systematic Assessment |
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| Catheter site oedema | General disorders | 24.1 | Systematic Assessment |
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| Fatigue | General disorders | 24.1 | Systematic Assessment |
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| Gait disturbance | General disorders | 24.1 | Systematic Assessment |
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| COVID-19 | Infections and infestations | 24.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | 24.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | 24.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | 24.1 | Systematic Assessment |
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| Amylase increased | Investigations | 24.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | 24.1 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | 24.1 | Systematic Assessment |
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| Lipase increased | Investigations | 24.1 | Systematic Assessment |
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| White blood cell count increased | Investigations | 24.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | 24.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | 24.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | 24.1 | Systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | 24.1 | Systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | 24.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | 24.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | 24.1 | Systematic Assessment |
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| Aphasia | Nervous system disorders | 24.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | 24.1 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | 24.1 | Systematic Assessment |
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| Encephalopathy | Nervous system disorders | 24.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | 24.1 | Systematic Assessment |
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| Peripheral sensory neuropathy | Nervous system disorders | 24.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | 24.1 | Systematic Assessment |
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| Syncope | Nervous system disorders | 24.1 | Systematic Assessment |
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| Tremor | Nervous system disorders | 24.1 | Systematic Assessment |
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| Confusional state | Psychiatric disorders | 24.1 | Systematic Assessment |
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| Euphoric mood | Psychiatric disorders | 24.1 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | 24.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 24.1 | Systematic Assessment |
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| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | 24.1 | Systematic Assessment |
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| Pain of skin | Skin and subcutaneous tissue disorders | 24.1 | Systematic Assessment |
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| Embolism | Vascular disorders | 24.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | 24.1 | Systematic Assessment |
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| Hypotension | Vascular disorders | 24.1 | Systematic Assessment |
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Study terminated early by sponsor before initiation of phase 2, so phase 2 outcome measures and endpoint data will not be reported.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bristol-Myers Squibb Study Director | Bristol-Myers Squibb | Please Email | Clinical.Trials@bms.com |
| Jan 29, 2024 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000708510 | repotrectinib |
| C560077 | trametinib |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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Repotrectinib 120 mg QD, Trametinib 1.0 mg QD |
| OG002 | Dose Level -2a | Repotrectinib 160 mg QD, Trametinib 1.0 mg QD |
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