Treatment of advanced solid tumors with RET gene abnormalities using TAS0953/HM06

Phase I/II Study of the Selective RET Inhibitor TAS0953/HM06 in Patients With Advanced Solid Tumors With RET Gene Abnormalities

This study is testing a new drug called TAS0953/HM06 to see if it can help people with advanced solid tumors that have RET gene changes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 244 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Taiho Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 21 sites (Orange, California and 20 other locations)
• Trial ID: NCT04683250 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety, pharmacokinetics, and efficacy of the RET inhibitor TAS0953/HM06 in patients with advanced solid tumors that have RET gene abnormalities. It consists of two phases: Phase 1 focuses on determining the Maximum Tolerated Dose (MTD) and identifying the Recommended Phase 2 Dose (RP2D), while Phase 2 will further assess the drug's effectiveness. Patients will be monitored for their response to treatment and any side effects experienced during the trial.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced solid tumors exhibiting RET gene abnormalities and an ECOG performance score of 0 or 1.

Not a fit: Patients with RET gene abnormalities who have previously been treated with RET selective inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with RET-altered solid tumors, potentially improving their outcomes.

How similar studies have performed: Other studies targeting RET gene abnormalities have shown promise, indicating that this approach may be effective.

Eligibility criteria

Ages Eligible for Study:

\- Adult patient (The definition of adulthood shall comply with the regulatory requirements of each region)

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 or cell pellet 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.

Where this trial is running

Orange, California and 20 other locations

• Chao Family Comprehensive Cancer Center — Orange, California, United States (Terminated)
• Stanford Cancer Center — Stanford, California, United States (Terminated)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Terminated)
• Henry Ford Hospital — Detroit, Michigan, United States (Terminated)
• START Midwest - Cancer & Hematology Centers of Western Michigan — Grand Rapids, Michigan, United States (Terminated)
• Laura and Isaac Perlmutter Cancer Center at NYU Langone Health — New York, New York, United States (Terminated)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Terminated)
• The Sarah Cannon Research Institute/Tennessee Oncology — Nashville, Tennessee, United States (Terminated)
• The University of Texas M. D. Anderson Cancer Center — Houston, Texas, United States (Terminated)
• National Cancer Center Hospital East — Kashiwa-shi, Chiba, Japan (Recruiting)
• Tohoku University Hospital — Sendai, Miyagi, Japan (Recruiting)
• Okayama University Hospital — Okayama, Okayama-ken, Japan (Recruiting)
• Kansai Medical University Hospital — Hirakata-shi, Osaka, Japan (Recruiting)
• Osaka International Cancer Institute — Osaka, Osaka, Japan (Recruiting)
• Shizuoka Cancer Center — Shizuoka, Shizuoka, Japan (Recruiting)
• National Cancer Center Hospital — Chuo-ku, Tokyo, Japan (Recruiting)
• The Cancer Institute Hospital of JFCR — Koto-ku, Tokyo, Japan (Recruiting)
• National Hospital Organization Kyushu Cancer Center — Fukuoka, Japan (Recruiting)
• Kanagawa Cancer Center — Kanagawa, Japan (Recruiting)
• Kurashiki Central Hospital — Okayama, Japan (Recruiting)
• Samsung Medical Center — Seoul, South Korea (Recruiting)

Study contacts

• Study coordinator: Kazuo Koba

Conditions RET-altered Non Small Cell Lung Cancer; RET-altered Solid Tumors