Study of RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities ((MARGARET))
RET-altered Non Small Cell Lung Cancer, RET-altered Solid Tumors
About this trial
This is an interventional treatment trial for RET-altered Non Small Cell Lung Cancer
Eligibility Criteria
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.
Sites / Locations
- Chao Family Comprehensive Cancer CenterRecruiting
- Stanford Cancer CenterRecruiting
- Massachusetts General HospitalRecruiting
- Henry Ford HospitalRecruiting
- START Midwest - Cancer & Hematology Centers of Western MichiganRecruiting
- Laura and Isaac Perlmutter Cancer Center at NYU Langone HealthRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- The Sarah Cannon Research Institute/Tennessee OncologyRecruiting
- The University of Texas M. D. Anderson Cancer CenterRecruiting
- National Cancer Center Hospital EastRecruiting
- National Cancer Center HospitalRecruiting
- The Cancer Institute Hospital of JFCRRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
TAS0953/HM06 Phase 1
TAS0953/HM06 Phase 2
Dose escalation and dose expansion until recommended Phase 2 dose determined
Treatment phase at recommended Phase 2 dose in three different populations