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

NCT ID: NCT04683250

Last Updated: 2025-03-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

244 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-16

Study Completion Date

2031-03-31

Brief Summary

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Phase 1 and 2 trial to study the safety, pharmacokinetics, and efficacy of TAS0953/HM06 in patients with advanced solid tumors with RET gene abnormalities. Phase 1 aims to determine the Maximum Tolerated Dose (MTD) and identify the Recommended Phase 2 Dose (RP2D) to be used in phase 2.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Dose escalation phase followed by a dose expansion phase (Phase 1), then followed by a Phase 2 at the recommended dose
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TAS0953/HM06 Phase 1

Dose escalation and dose expansion until recommended Phase 2 dose determined

Group Type EXPERIMENTAL

TAS0953/HM06

Intervention Type DRUG

Phase 1: oral, starting dose 20mg twice a day, until recommended phase 2 dose, continuous daily dosing, cycles lasting 21 days

TAS0953/HM06 Phase 2

Treatment phase at recommended Phase 2 dose in three different populations

Group Type EXPERIMENTAL

TAS0953/HM06

Intervention Type DRUG

Phase 2: oral, recommended dose twice a day, continuous daily dosing, cycles lasting 21 days

Interventions

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TAS0953/HM06

Phase 1: oral, starting dose 20mg twice a day, until recommended phase 2 dose, continuous daily dosing, cycles lasting 21 days

Intervention Type DRUG

TAS0953/HM06

Phase 2: oral, recommended dose twice a day, continuous daily dosing, cycles lasting 21 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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


* 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.


* 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

* 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.


* Presence of known EGFR, KRAS, ALK, HER2, ROS1, BRAF and METex14 activating mutations.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Taiho Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status TERMINATED

Stanford Cancer Center

Stanford, California, United States

Site Status TERMINATED

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status TERMINATED

Henry Ford Hospital

Detroit, Michigan, United States

Site Status TERMINATED

START Midwest - Cancer & Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

Site Status TERMINATED

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, United States

Site Status TERMINATED

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status TERMINATED

The Sarah Cannon Research Institute/Tennessee Oncology

Nashville, Tennessee, United States

Site Status TERMINATED

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, United States

Site Status TERMINATED

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

Site Status RECRUITING

Tohoku University Hospital

Sendai, Miyagi, Japan

Site Status RECRUITING

Okayama University Hospital

Okayama, Okayama-ken, Japan

Site Status RECRUITING

Kansai Medical University Hospital

Hirakata-shi, Osaka, Japan

Site Status RECRUITING

Osaka International Cancer Institute

Osaka, Osaka, Japan

Site Status RECRUITING

Shizuoka Cancer Center

Shunto-gun, Shizuoka, Japan

Site Status RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Site Status RECRUITING

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan

Site Status RECRUITING

Countries

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United States Japan

Central Contacts

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Kazuo Koba

Role: CONTACT

+08 8010113399

Facility Contacts

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Kiyotaka Yoh, MD

Role: primary

+81-4-7133-1111

Eisaku Miyauchi, MD

Role: primary

+81-22-717-8539

Kadoaki Ohashi, MD

Role: primary

+81-86-223-7151

Takayasu Kurata, MD

Role: primary

+81-72-804-0101

Kazumi Nishino, MD

Role: primary

+81-6-6945-1181

Akira Ono, MD

Role: primary

+81-55-989-5222

Yuki Shinno, MD

Role: primary

+81-3-3542-2511

Shigehisa Kitano, MD

Role: primary

+81-3-3520-0111

Other Identifiers

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HM06-19-26

Identifier Type: -

Identifier Source: org_study_id

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