Clinical Trial - NCT03093116

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

Recruiting

Sponsor: Turning Point Therapeutics, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03093116

Protocol Info

Short Description: Phase 1/2 TPX-0005 in Solid Tumors with ALK, ROS1, OR NTRK1-3
Long Description: 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)
MGH Status: Open
Sponsor: TP Therapeutics
Disease Program: Thoracic

Next Steps


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Purpose

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. 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 an ALK, 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 an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
Condition Title Intervention Phase
Locally Advanced Solid Tumors Metastatic Solid Tumors Oral repotrectinib (TPX-0005) Phase 1/Phase 2
Study Type Interventional
Official Title 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)

Primary Outcome Measures

Define the Maximum Tolerated Dose (MTD) [Time Frame: Within 28 days of the first repotrectinib (TPX-0005) dose for each patient.] [Designated as safety issue: ]

Define the Recommended Phase 2 Dose (RP2D) [Time Frame: Within 28 days of the first repotrectinib (TPX-0005) dose for each patient.] [Designated as safety issue: ]

Overall Response Rate (ORR) [Time Frame: Two to three years after starting treatment for each patient.] [Designated as safety issue: ]


Secondary Outcome Measures

To determine the effect of food on the AUC of repotrectinib (TPX-0005). (Phase 1) [Time Frame: Two to three months after starting treatment for each patient.] [Designated as safety issue: ]

To determine the preliminary objective response rate (ORR) [Time Frame: Approximately three years.] [Designated as safety issue: ]

To determine the duration of response (DOR) [Time Frame: Approximately three years.] [Designated as safety issue: ]

To determine the clinical benefit rate (CBR) [Time Frame: Approximately three years.] [Designated as safety issue: ]

To determine the progression free survival (PFS). [Time Frame: Approximately three years.] [Designated as safety issue: ]

To determine the overall survival (OS). [Time Frame: Approximately three years.] [Designated as safety issue: ]

To determine the intracranial objective response rate. [Time Frame: Approximately three years.] [Designated as safety issue: ]

Estimated Enrollment: 450
Study Start Date: February 2017
Estimated Study Completion Date: March 2022
Estimated Primary Completion Date: December 2020
Arms Assigned Interventions

Experimental:Phase1 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 Phase 2 Oral repotrectinib (TPX-0005): EXP-1 Cohort : ROS1+ NSCLC. No prior ROS1TKI allowed. Any prior lines of chemotherapy or immunotherapy are allowed. EXP-2 Cohort: ROS1+ NSCLC. Disease progression on one prior ROS1 TKI only. Any prior lines of chemotherapy or immunotherapy are allowed. EXP-3 Cohort: ROS1+ NSCLC. Disease progression on two prior ROS1 TKIs only. Any prior lines of chemotherapy or immunotherapy allowed. EXP-4 Cohort: ROS1+ or ALK+ non-NSCLC advanced solid tumors. No prior ROS1 or ALK TKIs allowed. Any prior lines of chemotherapy or immunotherapy allowed. EXP-5 Cohort: NTRK+ advanced solid tumors. No prior TRK TKI is allowed. EXP-6 Cohort: NTRK+ advanced solid tumors. No more than 2 prior TRK TKIs are allowed. Prior lines of chemotherapy or immunotherapy allowed.
Drug:Oral repotrectinib (TPX-0005)
Oral repotrectinib (TPX-0005) capsules.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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). In Phase 2, Age ≥12 is allowed.

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. Life expectancy ≥ 3 months.

Key Exclusion Criteria:

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 treatment

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03093116

Locations

  • United States, California
    • UC Irvine Health, Chao Family Comprehensive Cancer Center Orange, California, United States, 92868
  • United States, Colorado
    • University of Colorado Denver Aurora, Colorado, United States, 80045
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
  • United States, New York
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • Korea, Republic of,
    • Seoul National University Hospital Seoul, , Korea, Republic of, 110-744
    • Yonsei Cancer Center, Severance Hospital Seoul, , Korea, Republic of, 120-752
    • Samsung Medical Center Seoul, , Korea, Republic of, 135-710

Sponsors and Collaborators

Turning Point Therapeutics, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03093116
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Turning Point Therapeutics, Inc.:

ALK Gene Rearrangement

ROS1 Gene Rearrangement

NTRK 1/2/3 Gene Rearrangement

Additional relevant MeSH terms:

Neoplasms

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019