A Phase I Study of PARG Inhibitor FORX-428 in Patients With Advanced Solid Tumors With BRCA1/2 Mutations or Other DDR Deficiencies or High Replication Stress.
Study Identifier:
FORX-428-101
CT.gov Identifier:
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
N/A
Recruiting
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Study Summary
The goal of this interventional study is to evaluate the safety and tolerability of escalating doses of FORX-48 as monotherapy in patients with select advanced solid tumors with BRCA1/2 mutations or other DDR deficiencies or high replication stress, and to determine the maximum tolerated dose (MTD) and Recommended Cohort Expansion Dose (RCED) of FORX-428 as monotherapy.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I
Sex
Female & Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- 1. Patient must be >/=18 years of age at time of signing informed consent;
- 2. Patient has histologically and/or cytologically confirmed diagnosis of advanced or metastatic selected solid tumors.
- 3. Patient must have progressed on at least 1 prior line of therapy in the advanced or metastatic setting that is considered an appropriate standard of care. In general, if maintenance therapy is part of the standard of care, it should be considered as part of the "1 prior line of therapy in the advanced or metastatic setting" requirement;
- 4. Patient must fulfill genomic selection criteria: prior available documented evidence in tissue or blood (circulating tumor DNA [ctDNA]) of the genetic alterations indicated below. The Sponsor Medical Monitor or delegate must confirm eligibility based on the reported genomic alteration and applicable assay cut off criteria prior to patient enrollment.
- • Patients with BRCA1/2 mutations (germline or somatic, pathogenic or likely pathogenic) and other mutations signifying HR deficiency or high replication stress.
- • For Dose Expansion: Tumor types for Dose Expansion cohorts include a subset of tumors specified in Inclusion Criterion 3 as follows: i) Cohort 1: Advanced or metastatic breast cancer independent of hormone receptor status and documented evidence of prior treatment with a locally approved PARP inhibitor(s); ii) Cohort 2: Advanced or metastatic ovarian cancer with prior available documented evidence in tissue or blood (ctDNA) of specific genomic abnormalities.
- iii) Cohort 3: Advanced or metastatic breast cancer with prior available documented evidence in tissue or blood (ctDNA) of specific genomic abnormalities.
- Note: Diagnostic genetic testing for Dose Escalation/backfilling and Dose Expansion cohorts must meet the following requirements:
- • United States (US): Testing must have been performed using a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA)-certified laboratory developed test (LDT) or a Food and Drug Administration (FDA)-approved diagnostic test.
- 5. Patient has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at Clinical Screening; Note: Tumor lesions situated in a previously irradiated or otherwise locally treated area will be considered measurable provided that there has been clear imaging-based progression of the lesion since the time of local treatment.
- 6. Patient has adequate bone marrow and organ function, defined by the following laboratory results obtained within 14 days before first dose of study drug:
- * Platelet count >/=100 × 10^9/L (>/=100,000/μL) (absence of platelet transfusion within 1 week);
- * Hemoglobin >/=90 g/L (>/=5.6 mmol/L) (absence of red blood cell transfusion within 2 weeks);
- * Absolute neutrophil count >/=1.5 × 10^9/L (>/=1500/μL) (absence of growth factors within 2 weeks);
- * Aspartate aminotransferase and alanine aminotransferase
- * Total bilirubin
- * Estimated glomerular filtration rate >/=60 mL/min calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration Equation; and
- * Adequate coagulation test results defined by activated partial thromboplastin time
- 7. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 with >/=3 months of life expectancy for Dose Escalation cohorts, and an ECOG PS of 0 to 1 with >/=3 months of life expectancy for backfilling and Dose Expansion cohorts;
- 8. Patient is able to swallow tablets and has no gastrointestinal conditions affecting absorption.
Exclusion criteria
- 1. Patient has received anti-cancer treatment or an investigational agent
- 2. Patient has had previous exposure to a PARG inhibitor;
- 3. Patient has a history of other malignancy diagnosed 2 years at the time of consent and includes the following: completely resected cervical carcinoma in situ, basal or squamous cell skin cancer, ductal carcinoma in situ, superficial bladder cancer, or early-stage prostate cancer which has been adequately treated;
- 4. Patient has had major surgery within 30 days prior to first dose of study drug (with exceptions further defined in the protocol), or anticipation of major surgery during study treatment;
- 5. Patient has impaired cardiovascular function or clinically significant cardiovascular disease as further stipulated in the protocol;
- 6. Patient has uncontrolled HIV or hepatitis C infection;
- 7. Patient has known metastatic central nervous system malignant disease or leptomeningeal disease; Note: Patients previously treated for brain metastasis who are asymptomatic, receiving
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Manish Sharma
Status
Recruiting
Condition(s) Treated at Site
Solid Tumor
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Drew Rasco
Status
Recruiting
Condition(s) Treated at Site
Solid Tumor