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Trial record 1 of 8 for:    Turning Point Therapeutics
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A Study of Repotrectinib in Combination With Other Anticancer Therapies for the Treatment of Subjects With KRAS-Mutant Solid Tumors

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ClinicalTrials.gov Identifier: NCT05071183
Recruitment Status : Recruiting
First Posted : October 8, 2021
Last Update Posted : June 6, 2022
Sponsor:
Information provided by (Responsible Party):
Turning Point Therapeutics, Inc.

Brief Summary:
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)

Condition or disease Intervention/treatment Phase
KRAS Mutation-Related Tumors Metastatic Solid Tumor Advanced Solid Tumor Drug: TPX-0005 Drug: Trametinib Phase 1 Phase 2

Detailed Description:

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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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : September 23, 2021
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Trametinib

Arm Intervention/treatment
Experimental: TPX-0005 + Trametinib

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

Drug: TPX-0005
Oral TPX-0005 capsules
Other Name: repotrectinib

Drug: Trametinib
Oral trametinib tablets
Other Name: Mekinist




Primary Outcome Measures :
  1. Evaluate Safety and Tolerability [ Time Frame: Three years ]
    Evaluate the safety and tolerability of repotrectinib in combination with trametinib with treatment-related adverse events as assessed by CTCAE v5.0

  2. Define the Recommended Phase 2 Dose (RP2D) [ Time Frame: Approximately 22 months ]
  3. Define the objective response rate (ORR) [ Time Frame: Two to three years after first dose of Repotrectinib in combination with other anticancer therapies ]

Secondary Outcome Measures :
  1. Cmax (maximum plasma concentration) of repotrectinib in combination with trametinib [ Time Frame: Up to 24 hours post-dose ]
    Evaluate the maximum plasma concentration of repotrectinib in combination with trametinib

  2. AUC (area under plasma concentration time curve) of repotrectinib in combination with trametinib [ Time Frame: Up to 24 hours post-dose ]
    Determine the AUC of repotrectinib in combination with trametinib

  3. Determine the preliminary efficacy of repotrectinib in combination with trametinib measured by ORR as assessed per RECIST v1.1 [ Time Frame: Approximately three years ]
  4. Clinical benefit rate (CBR) [ Time Frame: Approximately three years ]
  5. Progression free survival (PFS) [ Time Frame: Approximately three years ]
  6. Duration of response (DOR) [ Time Frame: Approximately three years ]
  7. Time to response (TTR) [ Time Frame: Approximately three years ]
  8. Overall survival (OS) [ Time Frame: Approximately three years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 (or as required by local regulation).
  • Histological or cytological confirmation of unresectable or metastatic solid tumor malignancy harboring a KRAS mutation.
  • No more than 3 prior standard treatments appropriate for tumor type and stage of disease.
  • ECOG performance status ≤ 1.
  • Existence of measurable disease (according to Response evaluation criteria in solid tumors [RECIST v1.1] criteria).
  • Subjects with asymptomatic CNS metastases and/or asymptomatic leptomeningeal carcinomatosis are eligible.
  • Adequate organ function.

Exclusion Criteria:

  • Major surgery within four weeks of the start of treatment.
  • Previous other cancer requiring treatment within the previous two years.
  • Clinically significant cardiovascular disease.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) > 470 msec obtained from three ECGs and any factors that increase the risk of QTc prolongation or arrhythmic events
  • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG
  • Known clinically significant active infections not controlled with systemic treatment (bacterial, fungal, viral including HIV positivity).
  • Gastrointestinal disease or other malabsorption syndromes that would impact drug absorption.
  • Subjects being treated with or anticipating the need for treatment with strong CYP3A inhibitors or inducers.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05071183


Contacts
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Contact: Turning Point Therapeutics Medical Information +1 (855) 427-5878 medinfo@tptherapeutics.com

Locations
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United States, California
USC / Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Principal Investigator: Anthony El-Khoueiry, MD         
Hoag Memorial Hospital Recruiting
Newport Beach, California, United States, 92663
Principal Investigator: Anthony El-Khoueiry, MD         
United States, Colorado
Sarah Cannon Research Institute at HealthONE Recruiting
Denver, Colorado, United States, 80218
Principal Investigator: Gerald Falchook, MD, MS         
United States, Tennessee
Sarah Cannon Research Institute at Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Melissa Johnson, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: David Hong, MD         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Principal Investigator: Alexander Spira, MD, PhD         
Sponsors and Collaborators
Turning Point Therapeutics, Inc.
Investigators
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Study Director: Turning Point Therapeutics Turning Point Theraperutics
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Responsible Party: Turning Point Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05071183    
Other Study ID Numbers: TPX-0005-13
First Posted: October 8, 2021    Key Record Dates
Last Update Posted: June 6, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Turning Point Therapeutics, Inc.:
KRAS
KRAS-mutant
Metastatic Solid Tumor
Advanced Solid Tumor
Advanced/metastatic disease
Additional relevant MeSH terms:
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Neoplasms
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action