What side effects are associated with this type of intervention?

Common treatments for solid tumors, particularly those involving RET inhibitors like TAS0953/HM06, often include targeted therapies and chemotherapy. Known side effects of RET inhibitors can include hypertension, liver function abnormalities, diarrhea, and fatigue. Broader side effects for common solid tumor treatments may also encompass nausea, vomiting, neutropenia, anemia, and increased risk of infections. These side effects vary depending on the specific drug and patient condition.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of solid tumors with specific genetic abnormalities. For instance, selpercatinib and pralsetinib are RET inhibitors approved for treating non-small cell lung cancer (NSCLC) and thyroid cancers with RET gene fusions or mutations. These drugs work by specifically inhibiting the activity of the RET protein, which is involved in cell growth and division. Other targeted therapies for solid tumors include drugs like vemurafenib and dabrafenib, which target BRAF mutations in melanoma, and trastuzumab, which targets HER2-positive breast cancer.

What other types of research exist?

Promising alternatives to TAS0953/HM06 for solid tumors with RET gene abnormalities include selpercatinib and pralsetinib. Both have demonstrated efficacy in treating RET fusion-positive cancers and are approved for use in various solid tumors.

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Kinase Inhibitor

RET Inhibitor for Solid Cancers ((MARGARET) Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Helsinn Healthcare SA

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Phase I Dose-Escalation - Specific inclusion criteria: Advanced solid tumors

Phase I Dose-Expansion - Specific inclusion criteria: Locally advanced or metastatic non small cell lung cancer (NSCLC) patients with primary RET gene fusion and prior exposure to RET selective inhibitors

Must not have

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date of randomization until the date of death due to any cause, assessed up to an average of 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called TAS0953/HM06 for patients with advanced cancers that have specific genetic changes in the RET gene. The drug aims to block this gene to stop or slow down cancer growth. The initial part will find the safest dose, and the later part will test how well it works.

Who is the study for?

This trial is for adults with advanced solid tumors that have specific RET gene abnormalities. Participants should be in good physical condition (ECOG score of 0-1 or 2), have adequate organ function, and no major recent surgeries. They must not have certain genetic mutations like EGFR or KRAS, uncontrolled heart issues, or a history of severe heart rhythm problems.

What is being tested?

The study tests TAS0953/HM06's safety and effectiveness on patients with RET-related tumors. Phase 1 determines the safest high dose to use; Phase 2 uses this dose to further evaluate treatment effects.

What are the potential side effects?

While the side effects for TAS0953/HM06 are not detailed here, similar drugs often cause tiredness, nausea, changes in blood pressure or heartbeat, liver issues, and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have an advanced solid tumor.

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I have advanced lung cancer with a RET gene mutation and have been treated with RET inhibitors.

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I am fully active or have some restrictions but can still care for myself.

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My cancer has RET gene changes found in a biopsy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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Common Exclusion Criteria: - You have received experimental or anticancer treatment in the last 5 drug half-lives before starting the study. - You had major surgery within 4 weeks before starting the study or plan to have major surgery during the study. - You had whole brain radiotherapy within 14 days or other palliative radiotherapy within 7 days before starting the study, and still have side effects from it. - You have uncontrolled heart problems, high blood pressure, or a history of certain heart conditions. - Your corrected QT interval is longer than 470 milliseconds, or you have a history of certain heart rhythm problems. - You have taken strong CYP3A4 inhibitors within 1 week or strong CYP3A4 inducers within 3 weeks before starting the study.

Select...

My cancer does not have mutations in EGFR, KRAS, ALK, HER2, ROS1, BRAF, or METex14.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of randomization until the date of death due to any cause, assessed up to an average of 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of randomization until the date of death due to any cause, assessed up to an average of 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of randomization until the date of death due to any cause, assessed up to an average of 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1 (dose-escalation): Maximum Tolerated Dose (MTD)

Phase 2: Objective Response Rate (ORR) by independent data monitoring committee (IDMC)

Secondary study objectives

Phase 1 (dose expansion): Objective Response Rate (ORR) by IDMC

Phase 2: Central Nervous System (CNS) ORR (C-ORR)

Phase 2: Central Nervous System DOR (C-DOR)

+8 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: TAS0953/HM06 Phase 2Experimental Treatment1 Intervention

Treatment phase at recommended Phase 2 dose in three different populations

Group II: TAS0953/HM06 Phase 1Experimental Treatment1 Intervention

Dose escalation and dose expansion until recommended Phase 2 dose determined

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

RET inhibitors, such as TAS0953/HM06, work by targeting and blocking the RET signaling pathway, which is often abnormally activated in certain solid tumors. This targeted approach is significant for patients with RET gene abnormalities as it offers a personalized treatment option that can more effectively inhibit tumor growth and survival while potentially reducing side effects compared to conventional chemotherapy. Understanding these mechanisms is essential for developing new treatments and overcoming drug resistance, ultimately improving patient outcomes.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Therapeutic approaches for relapsed/refractory adult acute lymphoblastic leukemia (ALL), a review on monoclonal antibodies and targeted therapies.