Study of RET Inhibitor TAS0953/HM06 in Patients with Advanced Solid Tumors with RET Gene Abnormalities

Inclusion 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 biopsy or liquid biopsy. If deemed appropriate by the investigator, determination on a pleural cell block is also acceptable. - 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: - Patient with RET gene fusion : - Cohort 1, 3: locally advanced or metastatic NSCLC patients naïve to RET selective inhibitors and no prior systemic anti-cancer treatment. Patients who have been treated with neo-adjuvant or adjuvant chemotherapy may be included if it has been completed at least 6 months prior to the first dose of the study. - Cohort 2, 4: locally advanced or metastatic NSCLC patients with 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.