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Advanced Solid TumorsPhase 1NCT07356453

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

A Phase 1 study testing FORX-428 in people with Advanced Solid Tumors, run by FoRx Therapeutics AG at 8 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The goal of this interventional study is to evaluate the safety and tolerability of escalating doses of FORX-428 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
FORX-428
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
8 sitesUnited States
Study dates
22 Jul 2025to Apr 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
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  • 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;
  • 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 </=1.5 × ULN, international normalized ratio (INR) </=2.0 with the exception of INR 2 to 3 acceptable for patients on warfarin anticoagulation or direct oral anticoagulants.
  • 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;
  • Patient is able to swallow tablets and has no gastrointestinal conditions affecting absorption.

Who cannot join

  • 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.

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jens Wuerthner, MD, PhD contact

+1 513-579-9911

FORX-428-101@medpace.com

8 sites in 1 country

United States8 sites, 8 recruiting
  • NEXT - Virginia Cancer Specialists

    Fairfax, Virginia, 22031

    Study Coordinator, 703-783-4510

    Recruiting
  • START - Midwest

    Grand Rapids, Michigan, 49546

    Study Coordinator, 616-954-5554

    Recruiting
  • University of Texas - MD Anderson Cancer Center

    Houston, Texas, 77030

    Study Coordinator, 866-541-1846

    Recruiting
  • Stanford University Medical Center

    Palo Alto, California, 94304

    Study Coordinator, 650-723-4000

    Recruiting
  • Knight Cancer Institute

    Portland, Oregon, 97239

    Study Coordinator, 503-494-8311

    Recruiting
  • START - San Antonio

    San Antonio, Texas, 78229

    Study Coordinator, 210-593-5250

    Recruiting
  • University of California, San Francisco

    San Francisco, California, 94143

    Study Coordinator, 888-689-8273

    Recruiting
  • Washington University St. Louis

    St Louis, Missouri, 63108

    Study Coordinator, 800-600-3606

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1 Study of PARG Inhibitor FORX-428 in Patients With Advanced Solid Tumors With BRCA1/2 Mutations or Other DDR Deficiencies or High Replication Stress.

The goal of this interventional study is to evaluate the safety and tolerability of escalating doses of FORX-428 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.

Read the detailed description

The primary objective of the Expansion cohorts (Part 2) of this study is to evaluate the preliminary anti-tumor activity of FORX-428 as monotherapy.

Secondary Outcome Measures:

The secondary objectives of Part 1 of this study are the following:

  • To evaluate the preliminary anti-tumor activity of FORX-428 as monotherapy;
  • To evaluate the PK profile of FORX-428 when administered as monotherapy; and
  • To evaluate a FORX-428-induced effect on heart rate-corrected QT interval (QTc).

The secondary objectives of Part 2 of this study are the following:

  • To evaluate the safety and tolerability of FORX-428 as monotherapy; and
  • To evaluate the PK profile of FORX-428 when administered as monotherapy.
Being tested
FORX-428

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FORX-428Drug

    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.

Study groups in NCT07356453
Study groupRoleWhat they receive
First-in-human single-arm, open-label, multicenter Phase 1 dose escalation/expansion cohort study.ExperimentalFORX 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.
Receives: Drug: FORX-428

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 1 year.

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

    Measured: 1 year.

  3. 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

    Measured: 1 year.

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

    Measured: 1 year.

  5. 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

    Measured: 1 year.

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

    Measured: 1 year.

  7. 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

    Measured: 1 year.

  8. 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

    Measured: 1 year.

  9. 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

    Measured: 1 year.

  10. 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

    Measured: 1 year.

  11. Dose Expansion Phase: Tumor response: Overall Survival (OS)

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

    Measured: 1 year.

Secondary outcomes (27)
  1. Dose Escalation Phase: Tumor response: Overall Response Rate (ORR)

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

    Measured: 1 year.

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

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

    Measured: 1 year.

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

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

    Measured: 1 year.

  4. Dose Escalation Phase: Tumor response: best change in tumor size

    Best change in tumor size will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Measured: 1 year.

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

    Measured: 1 year.

  6. Dose Escalation Phase: Tumor response: Overall Survival (OS)

    Measured: 1 year.

  7. Dose Escalation Phase: Determination of plasma concentrations of FORX-428

    Measured: 1 year.

  8. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma (maximum plasma concentration [Cmax])

    Measured: 1 year.

  9. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma (time to maximum concentration [Tmax])

    Measured: 1 year.

  10. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma area under the plasma concentration curve [AUC] from time 0 to the time of last quantifiable plasma concentration [AUC0 t]

    Measured: 1 year.

  11. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma area under the plasma concentration curve [AUC] from time 0 to time τ [AUCτ]

    Measured: 1 year.

  12. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma area under the plasma concentration curve [AUC] from time 0 to infinity [AUC∞]

    Measured: 1 year.

  13. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma apparent first-order terminal elimination rate constant [λz]

    Measured: 1 year.

  14. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma terminal elimination half-life [t½]

    Measured: 1 year.

  15. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma mean residence time (MRT)

    Measured: 1 year.

  16. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma apparent clearance [CL/F]

    Measured: 1 year.

  17. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma apparent volume of distribution [Vz/F]

    Measured: 1 year.

  18. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma peak to trough fluctuation [PTF]

    Measured: 1 year.

  19. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma ratio of AUC [RAUC]

    Measured: 1 year.

  20. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma ratio of Cmax [RCmax]

    Measured: 1 year.

  21. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma average plasma concentration at steady state [Css av]

    Measured: 1 year.

  22. Dose Escalation Phase: PK parameters of FORX-428 when administered as monotherapy in plasma trough plasma concentration [Ctrough]

    Measured: 1 year.

  23. Dose Escalation Phase: Determination of concentration-QTc

    Measured: 1 year.

  24. Dose Expansion Phase: Incidence of treatment-emergent serious adverse events (TESAEs) 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

    Measured: 1 year.

  25. Dose Expansion Phase: Incidence of treatment discontinuations and treatment modifications due to AEs and laboratory abnormalities

    Measured: 1 year.

  26. Dose Expansion 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

    Measured: 1 year.

  27. Dose Expansion Phase: PK parameters of FORX-428 when administered as monotherapy in plasma (Cmax, tmax, AUC0 t, AUCτ, AUC∞, λz, t½, MRT, CL/F, Vz/F, PTF, RAUC, RCmax, Css av, and Ctrough, as applicable)

    Measured: 1 year.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jan 2026
  2. Study start22 Jul 2025
  3. Primary completionJun 2027 (estimated)
  4. Study completionApr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07356453
Sponsor's protocol ID
FORX-428-101
Status last verified
Sep 2026
First submitted
23 Dec 2025
Last updated
10 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing FORX-428 in people with Advanced Solid Tumors, run by FoRx Therapeutics AG at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jens Wuerthner, MD, PhD (+1 513-579-9911, FORX-428-101@medpace.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation Phase: Incidence of Dose-Limiting Toxicities (DLTs) (time frame: 1 year.). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.

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