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

Launched by TAIHO PHARMACEUTICAL CO., LTD. · Dec 23, 2020

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called TAS0953/HM06 for patients with advanced solid tumors that have specific changes in the RET gene, which can affect how these cancers grow. The trial aims to find out how safe the drug is, how well it works, and the best dose to use. It is currently looking for participants, including adults aged 65 to 74 and all genders, who have certain types of lung cancer or other solid tumors that have not responded well to previous treatments.

To be eligible, participants should have a good performance status (meaning they can carry out daily activities), and their tumors must have been tested for RET gene abnormalities. They should also have experienced disease progression after receiving other treatments or be unable to take those treatments. Throughout the study, participants will receive the medication and be closely monitored for any side effects and how their disease responds. It's important to note that individuals with certain other genetic mutations or those who have had recent major surgeries or therapies may not be able to join the trial.

Gender

ALL

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 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.