A Study of PARG Inhibitor FORX-428 in Patients With Advanced Solid Tumors.

NCT07356453 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: FORX-428-101
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (11)

• Dose Escalation Phase: Incidence of Dose-Limiting Toxicities (DLTs)

  1 year.

• Dose Escalation Phase: Incidence of treatment-emergent serious adverse events (TESAEs)

  1 year.

• Dose Escalation Phase: Incidence and severity of Treatment-emergent adverse event (TEAEs) and laboratory abnormalities

  Adverse events will be recorded and severity graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  1 year.

• Dose Escalation Phase: Incidence of treatment discontinuations and treatment modifications due to adverse events (AEs) and laboratory abnormalities

  1 year.

• Dose Escalation Phase: Change in vital signs measurements, clinical laboratory assessment, 12-lead electrocardiograms (ECGs), physical examinations (including Eastern Cooperative Oncology Group [ECOG] Performance Status [PS]), and urinalyses

  1 year.

• Dose Escalation Phase: Establishing the Maximum Tolerated Dose (MTD) and Recommended Cohort Expansion Dose (RCED) of FORX-428 administered as monotherapy

  1 year.

• Dose Expansion Phase: Tumor response: Best Overall Response (BOR)

  BOR will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  1 year.

• Dose Expansion Phase: Tumor response: Overall Response Rate (ORR)

  ORR will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  1 year.

• Dose Expansion Phase: Tumor response: Disease Control Rate (DCR)

  DCR will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  1 year.

• Dose Expansion Phase: Tumor response: Progression-free Survival (PFS)

  PFS will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  1 year.

• Dose Expansion Phase: Tumor response: Overall Survival (OS)

  OS will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  1 year.

Secondary Outcomes (27)

• Dose Escalation Phase: Tumor response: Overall Response Rate (ORR)

  1 year.

• Dose Escalation Phase: Tumor response: Best Overall Response (BOR)

  1 year.

• Dose Escalation Phase: Tumor response: Disease Control Rate (DCR)

  1 year.

• Dose Escalation Phase: Tumor response: best change in tumor size

  1 year.

• Dose Escalation Phase: Tumor response: Progression-free Survival (PFS)

  1 year.

Study Arms (1)

First-in-human single-arm, open-label, multicenter Phase 1 dose escalation/expansion cohort study.

EXPERIMENTAL

FORX 428 dose levels planned in the study: Dose Level 1: 30 mg, daily; Dose Level 2: 60 mg, daily; Dose Level 3: 120 mg, daily; Dose Level 4: 200 mg, daily; Dose Level 5: 300 mg, daily; and Dose Level 6: 400 mg, daily. Following the selection of the Recommended Cohort Expansion Dose during Part 1 of the study, new patients will be included in 3 cohorts, with simultaneous parallel enrollment. Patients will be allowed to continue to receive FORX-428 monotherapy until disease progression or unacceptable toxicity. Part 2 will include approximately up to 29 evaluable patients in each expansion cohort as determined by the Simon's optimal 2-stage design. In Stage 1 of each cohort of Part 2, a total number of 10 patients will be accrued. If there are 1 or fewer responses by RECIST version 1.1 among these 10 patients, further enrollment in that cohort will be halted for futility. Otherwise, an additional 19 patients will be accrued per cohort in Stage 2 of Part 2.

Drug: FORX-428

Interventions

FORX-428 DRUG

FORX-428 drug product is formulated as immediate release tablets for oral administration in 3 dosage strengths containing 10 mg, 50 mg, and 100 mg FORX-428 drug substance.

First-in-human single-arm, open-label, multicenter Phase 1 dose escalation/expansion cohort study.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be \>/=18 years of age at time of signing informed consent;
• Patient has histologically and/or cytologically confirmed diagnosis of advanced or metastatic selected solid tumors.
• 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;
• 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.
• 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.
• 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.
• 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 \</=2.5 × upper limit normal (ULN) or \</=5 × ULN for patients with liver metastases;
• Total bilirubin \</=1.5 × ULN, or \</=3.0 × ULN for patients with liver metastases or Gilbert's syndrome;

You may not qualify if:

• Patient has received anti-cancer treatment or an investigational agent \</=14 days or 5 half-lives prior to first dose, whichever is shorter, or patient has received immunotherapy \</=28 days prior to first dose; Note: Localized radiotherapy given with palliative intent is allowed and should be completed 1 week or more before receiving the first dose of FORX-428. It may also be allowed after the dose-limiting toxicity (DLT) Observation Period, pending discussion with the Sponsor Medical Monitor or delegate and their approval.
• Patient has had previous exposure to a PARG inhibitor;
• Patient has a history of other malignancy diagnosed \</=5 years prior to consent, except for any locally occurring cancer that has been treated with curative intent with no evidence of disease for \>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;
• 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;
• Patient has impaired cardiovascular function or clinically significant cardiovascular disease as further stipulated in the protocol;
• Patient has uncontrolled HIV or hepatitis C infection;
• Patient has known metastatic central nervous system malignant disease or leptomeningeal disease; Note: Patients previously treated for brain metastasis who are asymptomatic, receiving \</=10 mg/day prednisone equivalent, not requiring anti-epileptic therapy, and without evidence of radiological progression for at least 4 weeks are allowed.

Sponsors & Collaborators

• FoRx Therapeutics AG: lead

Study Sites (8)

Stanford University Medical Center

Palo Alto, California, 94304, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

START - Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

Washington University St. Louis

St Louis, Missouri, 63108, United States

RECRUITING

Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

START - San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

NEXT - Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Central Study Contacts

Jens Wuerthner, MD, PhD

CONTACT

+1 513-579-9911; FORX-428-101@medpace.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2025
• First Posted: January 21, 2026
• Study Start: July 22, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)