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)

Phase 2

Recruiting

Conditions: Advanced solid Tumors harboring ALK, ROS1 or NTRK1-3 rearrangements
Advanced solid tumors. Cancer

Registration Number: NL-OMON54586

Lead Sponsor: Turning Point Therapeutics (a wholly owned subsidiary of Bristol Myers Squibb company)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 23

Inclusion Criteria

- Histologically or cytologically confirmed diagnosis of locally advanced, or
metastatic solid tumor (including primary CNS tumors) that harbors a ROS1 or
NTRK1-3 gene fusion.

- Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by
either a) an approved medical device OR b) a non-approved medical device (for
details please see the protocol).

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.

- Age >= 12 (or age >=20 as required by local regulation)
Sponsor confirms that only persons 18 years of age and older will be enrolled
in the Netherlands

- At least 1 measurable target lesion according to RECIST (v1.1) prospectively
confirmed by Blinded Independent Central Radiology Review (BICR), selected by
the Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable target
lesion >= 10 mm as defined by RECIST (v1.1) are eligible.

Exclusion Criteria

1. Concurrent participation in another therapeutic clinical trial. 2.
Symptomatic brain metastases or leptomeningeal involvement. 3. History of
previous cancer requiring therapy within the previous 2 years, except for
squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma
that has been completely resected. 4. Major surgery within 4 weeks of start of
repotrectinib treatment. Radiation therapy (except palliative to relieve bone
pain) within 2 weeks of study entry. Palliative radiation (<=10 fractions) must
have been completed at least 48 hours prior to study entry. 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 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 (QTc) > 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 requiring ongoing treatment (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 on drug absorption. 9. Peripheral
neuropathy, paresthesia, dizziness, dysgeusia, muscle weakness, ataxia 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. 11.
Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
study drug administration, or that may interfere with the interpretation of
study results and, in the judgment of the Investigator, would make the subject
inappropriate for entry into this study, or could compromise protocol
objectives in the opinion of the Investigator and/or Turning Point
Therapeutics. 12. Current use or anticipated need for drugs that are known to
be strong CYP3A inhibitors or inducers as listed in Appendix 5. 13. Additional
exclusion criteria for subjects participating in the midazolam DDI sub-study:
in addition to the strong CYP3A inhibitors or inducers listed in Appendix 5,
subjects should not be taking any mode

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Endpoint for Phase 2:<br /><br>• Objective Response Rate (ORR) assessed by BICR using RECIST v1.1.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Endpoints for Phase 2:<br /><br>• Duration of Response (DOR), Time to Response (TTR), and Clinical Benefit Rate<br /><br>(CBR)<br /><br>• Intracranial tumor response in subjects with measurable brain metastases, as<br /><br>determined by BICR using modified RECIST v1.1<br /><br>• CNS Progression-Free Survival (CNS-PFS) in subjects with measurable brain<br /><br>metastases using modified RECIST v1.1<br /><br>• Progression-Free Survival (PFS), and OS</p><br>