FK-PC101 as Adjuvant Therapy for Men With High-Risk Prostate Cancer

This is a multicenter, adaptive, Phase 2, randomized, open-label study designed to evaluate the efficacy of FK-PC101 adjuvant therapy in men with localized prostate cancer who have undergone radical prostatectomy (RP). Subjects will undergo a 3-step screening and enrollment process. Following an initial safety run-in that will include at least three subjects assigned to receive FK-PC101 vaccine and monitored closely for safety, subjects randomized to the vaccine group will receive up to 7 doses of FK-PC101, starting at 2 months post-RP. Subjects in the control group will receive standard-of-care. All subjects will have assessments at 60 days (2 months), 90 days (3 months) and 180 days (6 months) and then continue with follow-up visits at 10, 14, 18, and 22 months after randomization.

FK-PC101 is an autologous cellular vaccine, with each product being manufactured from a portion of tumor from each subject's prostatectomy specimen. The primary endpoint of DFS will be compared with the control group, who will also meet all eligibility criteria but who do not receive any postoperative adjuvant therapy.

Subjects will undergo a three-step eligibility process with criteria prior to RP, immediately following RP and 2 months post-RP/immediately prior to randomization.

Subjects will be randomized in a 1:1 open-label fashion to the vaccine group and the control group. Subjects will be stratified based on pathologic nodal status (pN0 vs. pN1). Subjects in the vaccine group will initiate vaccine dosing with up to 7 doses given between Day 1 and Day 180 (on Days 1, 8, 15, 22, 60, 90 and 180). Subjects randomized to the control group will be followed through 8 follow-up visits through month 22 (2 years post-surgery).

Following disease recurrence, all subjects may be treated with other prostate cancer therapies as deemed appropriate. Subjects in the control group will be eligible to receive their vaccine after disease recurrence has been documented. For subjects in the control group who elect to receive their vaccine, it must be started within 1 year of randomization. The vaccine doses may be administered prior to, during, or following other prostate cancer therapies but will follow the same schedule as for the subjects in the vaccine group.

Inclusion criteria

• Has localized high-risk or very high-risk prostate cancer based on the NCCN v4.2023 classification.
• Has ≥3 prostate biopsy cores with ≥50% tumor involvement.
• Has PSA >4 ng/mL ≤28 days prior to enrollment.
• Has no evidence of distant metastases based on PSMA-PET/CT performed ≤28 days prior to enrollment.
• Is a candidate for radical prostatectomy, and scheduled radical prostatectomy date must be 3 to 14 days after enrollment.
• Has not received nor plans to receive neoadjuvant (preoperative) radiation therapy, androgen deprivation therapy (ADT), or any other anticancer therapy.
• Has a life expectancy >5 years.

Additional key eligibility criteria immediately postoperative for inclusion in the randomized population include:

• Stage >pT3a (tumor has extended outside of the prostate on one side).
• Gleason score of 8, 9, or 10 (high/very high) on prostatectomy specimen.
• Subjects with pT3b or pT4 tumors with a Gleason sum 7 (4+3) are eligible.
• Pelvic lymph node dissection (PLND) is required with either pN0 or pN1 nodal staging permitted.
• Subjects must have negative surgical margins or microscopic-only positive surgical margins.

Final eligibility criteria at 2 months postoperative for randomization include:

• FK-PC101 has been produced for the subject and meets all release specifications.
• An undetectable PSA (<0.04 ng/mL) on the most recent test performed prior to randomization (Day -4 to -7).
• No prior, current, or planned future postoperative or adjuvant XRT, hormonal therapy such as ADT, or any other anticancer therapy (future therapy should not be administered until evidence exists of prostate cancer disease recurrence [such as PSA recurrence]).
• Adequate organ function based on CBC and chemistry studies within 2 weeks of Day 1 (Day -14 to -7). Specific laboratory requirements include:

• Absolute neutrophil count (ANC) >1000/µL
• Platelet count >100,000/µL.
• Hemoglobin >8.0 gm/dL.
• Estimated glomerular filtration rate (eGFR) >60 mL/minute based on Cockcroft-Gault formula.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both <2 × upper limit of normal (ULN).
• Albumin >3.0 gm/dL.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions of the study.

Exclusion criteria

• Has an additional active malignancy that may confound the assessment of the study endpoints. If the subject has a past cancer history (active malignancy within 2 years prior to study entry) with substantial potential for recurrence, this must be discussed with the Sponsor before study entry. Note: Subjects with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer and carcinomas in situ (including breast DCIS, transitional cell carcinoma/NMIBC, anal carcinoma, and melanoma in situ).
• Is eligible for and elects to receive adjuvant therapy following RP.
• Has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association [NYHA] Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, pulmonary embolism or stroke within 6 months prior to study entry, uncontrolled hypertension, or clinically significant arrhythmias not controlled by medication).
• Has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the subject at significant risk for pulmonary complications during the study.
• Has known metastases, such as bone, visceral, or brain or leptomeningeal metastases.
• Has an active autoimmune disease or Grade ≥3 pneumonitis that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) or treatment with drugs (e.g., neomercazol, carbamazole) that function to decrease the generation of thyroid hormone by a hyperfunctioning thyroid gland (e.g., in Graves' disease) is not considered a form of systemic treatment of an autoimmune disease.
• Is currently receiving systemic steroid therapy at a prednisone equivalent dose of >10 mg daily for at least 1 week or other form of immunosuppressive therapy within 7 days prior to enrollment.
• Has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements.
• Is at risk for disseminated BCG infection or has previously demonstrated an allergic response to BCG or its components.
• Has known positive status for human immunodeficiency virus (HIV) or active or chronic Hepatitis (Hep) B or Hep C. Screening is not required.
• Has any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicity.