Phase I/II Study of the Selective RET Inhibitor TAS0953/HM06 in Patients with Advanced Solid Tumors with RET gene abnormalities

JRCT ID: jRCT2031200208

Registered date:23/11/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Solid tumor (Non-small cell lung cancer, and so on)
• Date of first enrollment: 18/02/2021
• Target sample size: 77
• Study type: Interventional

Intervention(s)

Phase1: oral, starting dose 20mg twice a day, until
recommended phase 2 dose, continuous daily
dosing, cycles lasting 21 days
Phase2: oral, recommended dose twice a day, continuous daily dosing, cycles lasting 21 days

Outcome(s)

Primary Outcome

- Maximum Tolerated Dose (MTD)
- Recommended Phase 2 dose (RP2D)
- Objective Response Rate (ORR) by independent central review (IRC)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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 at baseline.
- Adequate hematopoietic, hepatic and renal function.

Phase I Dose-Escalation :
- Measurable and/or non-measurable disease as determined by RECIST 1.1, as assessed by Investigator review.
- Patient must have documented progression of disease following existing therapies deemed by the Investigator to have demonstrated clinical benefit or unable to receive such therapies.
- If patient has brain and/or leptomeningeal metastases, he/she should have he/she should be asymptomatic.

Phase I Dose-Expansion - :
- Patient with RET gene fusion
Cohort 1: locally advanced or metastatic NSCLC patients naive to RET selective inhibitors and no prior systemic anti-cancer treatment
Cohort 2: 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, as assessed by Investigator review

Phase II
- Locally advanced or metastatic:
a. NSCLC patients with primary RET gene fusion and prior exposure to RET selective
inhibitors;
b. NSCLC patients with RET gene fusion and without prior exposure to RET selective inhibitors
c. 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, as assessed by Investigator review
- Available RET-gene abnormalities determined on tissue or liquid biopsy at baseline.
- If patient has brain and/or leptomeningeal metastases, he/she should have:
a) asymptomatic untreated brain/leptomeningeal metastases off steroids and anticonvulsant for at least 7 days or
b) 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.

Exclude criteria

- Investigational agents or anticancer therapy within 5 halflives (or 1 half-life for long-lasting drugs such as anticancer antibodies and other biologic drugs, provided there are no residual toxicities) 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
- Patient who has received WBRT within 14 days or other palliative radiotherapy within 7 days prior to the first dose of study drug, or who has not recovered from side effects of such therapy, if in the opinion of the Investigator this is clinically meaningful.
- 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.
- Sustained over time 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 uncontrolled and persistent risk factors for TdP
- Treatment with strong CYP3A4 inhibitors within 1 week (7 days) prior to the first dose of study drug or strong CYP3A4 inducers within 3 weeks prior to the first dose of study drug.

Related Information

• Primary Sponsor: Masuda Noriyuki
• Secondary Sponsor: Helsinn Healthcare SA
• Secondary ID(s): NCT04683250