Combination of FOR46 and Enzalutamide for Advanced Prostate Cancer

A Phase 1b/2 Study of FOR46 in Combination With Enzalutamide in Patients With Metastatic Castration Resistant Prostate Cancer

This study is testing whether a new drug called FOR46 combined with enzalutamide can help men with advanced prostate cancer who haven't responded to previous treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: University of California, San Francisco (Academic / other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT05011188 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of FOR46 in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously progressed on abiraterone. The study consists of two phases: Phase 1b focuses on determining the maximum tolerated dose and recommended phase 2 dose of the combination, while Phase 2 aims to assess the composite response rate defined by a significant decline in serum PSA levels and objective tumor response. Participants will be monitored for overall survival and safety throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include men with histologically confirmed metastatic prostate adenocarcinoma who have experienced disease progression on prior androgen signaling inhibitors.

Not a fit: Patients who have previously received taxane-based chemotherapy for mCRPC may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced prostate cancer who have limited treatment alternatives.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in advanced prostate cancer, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed metastatic prostate adenocarcinoma.
2. Disease progression by PCWG3 criteria at study entry.
3. Prior progression by PCWG3 criteria on one or more androgen signaling inhibitors including abiraterone acetate, enzalutamide, apalutamide, and/or darolutamide.
4. No prior taxane-based chemotherapy for the treatment of mCRPC. Prior taxane use in the castration-sensitive prostate cancer (CSPC) setting allowed provided last dose \> 6 months prior to study entry.
5. Patients must be evaluable for the primary endpoint of composite response, and must have either serum PSA ≥ 2 ng/mL during Screening and/or measurable disease by RECIST 1.1 criteria.
6. Participants must be willing to undergo metastatic tumor biopsy during Screening. If there is no safely accessible metastatic lesion, this requirement will be waived.
7. Dose Expansion only: Participants must be willing to undergo CD46-directed Positron Emission Tomography (PET) imaging during Screening (Co-enrolling on NCT05245006, Groups B and C)
8. Castrate level of serum testosterone at study entry (\<50 ng/dL). Patients without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study.
9. No other systemic anti-cancer therapies administered other than LHRH analogue within 14 days or, 5 half-lives, whichever is shorter, prior to initiation of study treatment. Adverse events related to prior anti-cancer treatment related to therapies other than LHRH analogue must have recovered to Grade ≤ 1 with the exception of any grade alopecia. a. Patients receiving enzalutamide prior to study entry may continue treatment at their current enzalutamide dose level without requirement for wash-out period.
10. Age \>=18 years.
11. Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 (Karnofsky performance status \>= 70 percent (%)).
12. Demonstrates adequate organ function as defined below:

    1. Absolute neutrophil count ≥ 1,500/microliter (mcL).
    2. Platelets \>= 100,000/mcL and no platelet transfusions during the 14 days prior to first dose of FOR46.
    3. Hemoglobin \>= 8.0 grams per deciliter (g/dL) without red blood cell transfusion during the 14 days prior to first dose of FOR46.
    4. Total bilirubin \<=1.5 x institutional upper limit of normal (ULN), unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
    5. Aspartate aminotransferase (AST) /serum glutamic-oxaloacetic transaminase (SGOT) \<=3 x institutional institutional upper limit of normal (ULN).
    6. Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) =3 x ULN.
    7. Serum creatinine \<= 1.5 x institutional upper limit of normal OR Calculated creatinine clearance glomerular filtration rate (GFR) \>= 60 mL/min, calculated using the Cockcroft-Gault equation.
    8. Serum sodium level \>=130 mmol/L.
13. Ability to understand a written informed consent document, and the willingness to sign it.
14. Individuals with concurrent second malignancy requiring active treatment at study entry. Nonmelanoma skin cancer, non-muscle invasive bladder cancer, and other carcinomas-in-situ are allowable exceptions.
15. Patients must agree to use adequate contraception prior to the study, for the duration of study participation, and 60 days after last administration of study treatment. Adequate contraception includes:

    1. Patients who are sexually active should consider their female partner to be of childbearing potential if she has experienced menarche and is not postmenopausal (defined as amenorrhea \> 24 consecutive months) or has not undergone successful surgical sterilization. Even women who use contraceptive hormones (oral, implanted, or injected), an intrauterine device, or barrier methods (diaphragms, condoms, spermicide) should be considered to be of childbearing potential.
    2. Acceptable methods of contraception include continuous total abstinence, or double-barrier method of birth control (e.g. condoms used with spermicide, or condoms used with oral contraceptives). Periodic abstinence and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

1. Has received prior radiotherapy within 2 weeks of first dose of FOR46.
2. Prior treatment with FOR46 or another CD46-targeting therapeutic agent.
3. Prior histologic evidence of de novo or treatment-emergent small cell neuroendocrine prostate cancer. Pathologic assessment of baseline tumor biopsy performed during Screening is not required for determination of study eligibility.
4. Cardiac condition as defined as one or more of the following:

   1. Uncontrolled supraventricular arrhythmia or ventricular arrhythmia requiring treatment.
   2. New York Heart Association (NYHA) congestive heart failure class III or IV.
   3. History of unstable angina, myocardial infarction, or cerebrovascular accident within 6 months prior to Cycle 1, Day 1.
5. History of seizure or pre-disposing condition including:

   1. History of brain metastasis.
   2. Cerebrovascular accident (CVA) within 6 months prior to study entry.
   3. History of intracranial hemorrhage.
6. History of pneumonitis.
7. Is receiving systemic steroid therapy at a prednisone equivalent dose of \> 10 milligram daily or other form of immunosuppressive therapy within 7 days prior to first dose of study drug.
8. Has an active infection requiring intravenous antibiotics within 7 days prior to Cycle 1, Day 1.
9. Use of a prohibited concomitant medication within 7 days of first dose of FOR46, including:

   a. Strong inhibitor of CYP3A4 (boceprevir, clarithromycin, cobicistat, conivaptan, diltiazem, danoprevir/ritonavir, elvitegravir/ritonavir, grapefruit juice, idelalisib, indinavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, paritaprevir/ritonavir/ombitasvir and/or dasabuvir, posaconazole, ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, troleandomycin, and voriconazole).
10. Major surgery within 28 days prior to Cycle 1, Day 1. Minor procedures including biopsies, dental surgery, cataract surgery, or outpatient procedure are allowed.
11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Where this trial is running

San Francisco, California

• University of California, San Francisco — San Francisco, California, United States (Recruiting)

Study contacts

• Principal investigator: Rahul Aggarwal, MD — University of San Francisco
• Study coordinator: UCSF Genitourinary Medical Oncology

Conditions Metastatic Castration-resistant Prostate Cancer; Prostate Cancer; FOR46; Enzalutamide