Study of RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities
Purpose
Phase 1 and 2 trial to study the safety, pharmacokinetics, and efficacy of TAS0953/HM06 in patients with advanced solid tumors with RET gene abnormalities. Phase 1 aims to determine the Maximum Tolerated Dose (MTD) and identify the Recommended Phase 2 Dose (RP2D) to be used in phase 2.
Conditions
- RET-altered Non Small Cell Lung Cancer
- RET-altered Solid Tumors
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
Phase I - Common inclusion criteria for Dose-Escalation / Dose-Expansion: - Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 - Available RET-gene abnormalities determined on tissue or liquid biopsy - Documented progression of disease following existing therapies deemed by the Investigator to have demonstrated clinical benefit or unable to receive such therapies. - Adequate hematopoietic, hepatic and renal function Phase I Dose-Escalation - Specific inclusion criteria: - Advanced solid tumors - Measurable and/or non-measurable disease as determined by RECIST 1.1 - If patient has brain and/or leptomeningeal metastases, (s)he should be asymptomatic. Phase I Dose-Expansion - Specific inclusion criteria: - Locally advanced or metastatic non small cell lung cancer (NSCLC) patients with primary RET gene fusion and prior exposure to RET selective inhibitors - Measurable disease as determined by RECIST 1.1 - If patient has brain and/or leptomeningeal metastases,(s)he should have: - asymptomatic untreated brain/leptomeningeal metastases off steroids and anticonvulsant for at least 7 days or - asymptomatic brain metastases already treated with local therapy and be clinically stable on steroids and anticonvulsant for at least 7 days before study drug administration. Phase II : - Available RET-gene abnormalities determined on tissue or liquid biopsy - Locally advanced or metastatic: - NSCLC patients with primary RET gene fusion and prior exposure to RET selective inhibitors; - NSCLC patients with RET gene fusion and without prior exposure to RET selective inhibitors - patients with advanced solid tumors that harbour RET gene abnormalities (other than NSCLC patients with primary RET gene fusions) and has failed all the available therapeutic options - Eastern Cooperative Oncology Group (ECOG) performance score of 0-2 - Measurable disease as determined by RECIST 1.1 - If patient has brain and/or leptomeningeal metastases,(s)he should have: - asymptomatic untreated brain/leptomeningeal metastases off steroids and anticonvulsant for at least 7 days or - asymptomatic brain metastases already treated with local therapy and be clinically stable on steroids and anticonvulsant for at least 7 days before study drug administration. - Adequate hematopoietic, hepatic and renal function
Exclusion Criteria
Common exclusion criteria for Phase 1 and Phase 2 - Investigational agents or anticancer therapy within 5 half-lives prior to the first dose of study drug - Major surgery (excluding placement of vascular access) within 4 weeks prior to the first dose of study drug or planned major surgery during the course of study treatment. - Whole Brain Radiotherapy within 14 days or other palliative radiotherapy within 7 days prior to the first dose of study drug, or persisting side effects of such therapy, in the opinion of the Investigator. - Clinically significant, uncontrolled, cardiovascular disease including myocardial infarction within 3 months prior to Day 1 of Cycle 1, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic Congestive Heart Failure (CHF) New York Heart Association (NYHA) class III-IV, and severe uncontrolled arterial hypertension, according to the Investigator's opinion. - QT interval corrected using Fridericia's formula (QTcF) >470 msec; personal or family history of prolonged QT syndrome or history of Torsades de pointes (TdP). History of risk factors for TdP - Treatment with strong CYP3A4 inhibitors within 1 week prior to the first dose of study drug or strong CYP3A4 inducers within 3 weeks prior to the first dose of study drug. Phase I Dose-Expansion - and Phase II specific exclusion criteria: - Presence of known EGFR, KRAS, ALK, HER2, ROS1, BRAF and METex14 activating mutations.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Dose escalation phase followed by a dose expansion phase (Phase 1), then followed by a Phase 2 at the recommended dose
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental TAS0953/HM06 Phase 1 |
Dose escalation and dose expansion until recommended Phase 2 dose determined |
|
Experimental TAS0953/HM06 Phase 2 |
Treatment phase at recommended Phase 2 dose in three different populations |
|
Recruiting Locations
Boston, Massachusetts 02114
Justin Gainor, MD
617-724-4000
More Details
- Status
- Recruiting
- Sponsor
- Helsinn Healthcare SA