Phase 1 Study of the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Clinical Activity of RP-6306 Alone or in Combination with RP-3500 in Patients with Advanced Solid Tumors - MYTHIC study

Repare Therapeutics0 sites180 target enrollmentMay 5, 2021

ConditionsAdvanced solid tumors with CCNE1 amplification or deleterious mutations in FBXW7 or other proprietary gene MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Advanced solid tumors with CCNE1 amplification or deleterious mutations in FBXW7 or other proprietary gene
Sponsor: Repare Therapeutics
Enrollment: 180
Status: Active, not recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

May 5, 2021

End Date

TBD

Last Updated

2 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Repare Therapeutics

Eligibility Criteria

Inclusion Criteria

•1\. Written informed consent and assent, according to local guidelines, signed and dated by the participating patient or legal guardian prior to the performance of any study\-specific procedures, sampling, or analyses.
•2\. Male or female and \=12 years\-of\-age at the time of signature of the informed consent form (ICF).
•3\. Lansky performance status \=50 for patients \=16 years of age, or ECOG score of 0, 1, or 2 (Module 2 ECOG 0 or 1\) for patients \>16 years of age.
•4\. All patients must have locally advanced or metastatic resistant or refractory solid tumors. Patients \<18 years\-of\-age will be eligible only if standard or available curative therapy does not exist. Patients \=18 years\-of\-age are eligible if, in the opinion of the investigator, the patient is not a candidate for, or would be unlikely to tolerate or derive significant clinical benefit from, appropriate standard\-of\-care therapy, or if the patient declines standard\-of\-care therapy.
•5\. Patients \<18 years of age must weigh at least 40 kg.
•6\. Archived tumor tissue sample available or lesion that can be safely biopsied if the archival sample is not available.
•7\. All patient’s tumors, except for types of endometrial cancer listed in criteria \#8, must have evidence of at least one of the following as reported by a local CLIA\-certified or equivalent (ex\-United States \[US]) laboratory and centrally confirmed by PODS:
•a. CCNE1 amplification (non\-equivocal) as determined by either a tumor or plasma NGS test, or FISH
•b. FBXW7 deleterious mutations identified by either a tumor or plasma NGS test
•c. Proprietary gene deleterious mutations identified by either a tumor or plasma NGS test

Exclusion Criteria

•1\. Chemotherapy or small molecule antineoplastic agent given within 21 days or \<5 half\-lives, whichever is shorter, prior to first dose of study drug. For drugs for which 5 half\-lives is \=21 days, a minimum of 10 days between termination of the prior treatment and administration of RP\-6306 treatment is required. For patients with breast or prostate cancer, continuation of long\-term luteinizing hormone\-releasing hormone (LHRH), gonadotrophin releasing hormone (GnRH), or previously prescribed Receptor Activator of Nuclear Factor kB Ligand (RANKL) inhibitor are allowed if these medications were prescribed for at least 3 months before trial entry. Bisphosphonates are allowed if prescribed at least 28 days prior to enrollment.
•2\. History or current condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the patient’s participation for the full duration of the study treatment.
•3\. Patients who are pregnant or breastfeeding.
•4\. Known sensitivity to any of the ingredients of RP\-6306 (and RP\-3500 for Module 2\).
•5\. Patient who are unable to swallow oral medications.
•6\. Life\-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction (such as ascites requiring drainage within 4 weeks prior to enrollment, coagulopathy, or encephalopathy), or other reasons which, in the investigator’s opinion, could compromise the participating patient’s safety, or interfere with or
•compromise the integrity of the study outcomes.
•7\. Major surgery (excluding placement of vascular access) within 4 weeks prior to first dose of RP\-6306\.
•8\. Uncontrolled, symptomatic brain metastases. Patients with previously treated brain metastases may participate provided the metastases are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of study drug and any neurologic symptoms are controlled and stable), have no evidence of new or enlarged brain metastases, and are clinically stable and off steroids for at least 7 days prior to study drug.
•9\. Uncontrolled hypertension (systolic blood pressure \[BP] \=160 mmHg; diastolic BP \=100 mmHg) despite adequate treatment prior to first dose of RP\-6306 (and RP\-3500 for Module 2\).