Phase 1 study for people with Prostate Cancer

Reproduced exactly, unedited. Written for researchers rather than for patients.

Inclusion Criteria:

1. Male, age 18 to 80 years, inclusive.

2. Histologically or cytologically confirmed adenocarcinoma of the prostate. Adenocarcinoma with small cell or neuroendocrine (NE) features is permitted, provided that usual adenocarcinoma is the predominant component (a known subset may be acceptable). However, pure small cell carcinoma, carcinoid tumor, mixed NE carcinoma, or large cell NE carcinoma is disallowed.

3. Androgen pathway modulation-resistant disease, defined as disease progression while receiving ongoing androgen pathway modulation (e.g., androgen deprivation therapy [ADT], androgen receptor pathway inhibitors [ARPIs]). Disease progression may be documented by PSA progression, radiographic progression, consistent with PCWG4 principles and investigator judgment, in consultation with the Medical Monitor where appropriate.

   • All participants must have received (and be receiving) standard of care androgen deprivation treatment (surgical castration versus GnRH analogue or antagonist treatment); participants receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study. Participants must have a castrate serum level of testosterone (< 50 ng/dL or 1.7 nmol/L) at screening.
   • Disease progression must be documented based on available clinical evidence and investigator judgment and may be established using any one of the following criteria, as applicable:
   • PSA progression: PSA level increase from baseline / nadir, with a minimum rise of 0.2 ng/mL, confirmed by an additional rising PSA measurement performed. Alternative documentation of progression may be accepted following discussion with the Medical Monitor when confirmation is not feasible or may unnecessarily delay treatment.
   • Soft tissue / Visceral progression (lymph nodes, lung, liver, other viscera, prostate/prostate bed): Assessed according to RECIST 1.1.
   • Bone progression: As defined by PCWG4 criteria, two or more new lesions will constitute progression in bone. PSMA PET is not required for bone progression assessment.

4. Metastatic disease as evidenced by soft tissue lesions on baseline computed tomography (CT) scan / magnetic resonance imaging (MRI) of the chest, abdomen and pelvis, and/or bone metastases on baseline bone scan.

5. Asymptomatic or minimally symptomatic mAPMR. "Asymptomatic/minimally symptomatic" is defined by meeting all of the following criteria:

   • Controlled symptoms (e.g., opioids for cancer related pain stable for > 4 weeks, no need for urgent radiotherapy for symptomatic lesions).
   • No anticipated need for immediate alternative systemic therapy (e.g., taxane chemotherapy, olaparib, Lu-PSMA) to manage symptomatic progression in the judgment of the investigator.
   • Prior stereotactic ablative radiotherapy (SABR) is not required. If prior SABR has been received, acute treatment-related toxicities should have resolved and any treated lesions are not the sole sites used to determine progressive disease.

6. Prior exposure to androgen receptor pathway inhibitors (ARPIs) must meet one of the following criteria:

   • For traditional nonsteroidal antiandrogens (e.g., bicalutamide, nilutamide, flutamide): Participants should have discontinued such antiandrogen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to screening. In addition, participants who demonstrate an antiandrogen withdrawal response, defined as a >25% decline in PSA within 4-6 weeks after stopping the nonsteroidal antiandrogen, are not eligible until the PSA rises above the nadir observed after withdrawal.
   • For other ARPIs (e.g., enzalutamide, abiraterone, apalutamide, darolutamide): Participants must meet one of the following conditions:
   • No prior treatment with any of such ARPIs; or
   • Prior treatment with only one such ARPI and experienced only one documented disease progression while on that therapy, and the investigator assesses that the participant is suitable for switching to a different ARPI of this class; or
   • Currently receiving the first such ARPI (e.g., enzalutamide, abiraterone, apalutamide, darolutamide) and has radiographically stable disease but isolated PSA progression per PCWG4 criteria; or
   • Prior treatment with one such ARPI with documented disease progression, where the investigator determines that continuation of the same ARPI or switching to another ARPI is not expected to provide meaningful clinical benefit. Such participants may be eligible while continuing standard ADT without an ARPI, provided that no immediate alternative systemic anticancer therapy is clinically required.
   • For participants currently or previously treated with abiraterone, the concomitant corticosteroid (e.g., prednisone) used with abiraterone should also meet the requirements of Exclusion Criterion #3.

7. Life expectancy of at least 12 months.

8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and independent in activities of daily living (ADL).

9. Adequate hematologic, renal and liver function as evidenced at screening.

   • Hemoglobin ≥9.0 g/dL
   • Absolute neutrophil count ≥1.0×109/L
   • Platelet count ≥100×109/L
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (or ≤3.0×ULN for participants with tumor involvement in the liver)
   • Serum albumin ≥3.0 g/dL
   • Serum total bilirubin ≤1.5×ULN; participants with congenital bilirubinemia, such as Gilbert's syndrome, may enroll if conjugated bilirubin is ≤1.5×ULN
   • In the absence of anticoagulant therapy, prothrombin time (PT) or international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5×ULN
   • Creatinine < 175 µmol/L

10. No known history of human immunodeficiency virus infection (HIV) 1 and 2, human T-lymphotropic virus type 1 (HTLV-1), syphilis, active Hepatitis B or Hepatitis C.

11. If participant is sexually active, he must observe contraceptive/barrier requirements with:

    • documented bilateral orchiectomy, or
    • agreement to practice abstinence from penile-vaginal intercourse or use condoms/barrier protection from Screening until 12 months after the last dose of KMV002, and
    • agreement to refrain from sperm donation from Screening until 12 months after the last dose of KMV002, and
    • highly effective contraceptive methods applied to WOCBP who are sexual partners of male participants for the specified duration, in addition to male condom use, from Screening until 12 months after the last dose of KMV002.

12. Willing to comply with the study requirements and to provide written informed consent prior to the initiation of study procedures.

Exclusion Criteria:

1. The presence of known brain metastasis or leptomeningeal disease, malignant pleural effusions, or malignant ascites.

2. Toxicity related to prior anticancer therapy has not returned to Grade ≤1 or baseline levels (except for alopecia, vitiligo, Grade 2 peripheral neuropathy, radiation tissue fibrosis, radiation cystitis, and radiation proctitis).

3. Treatment with any of the following medications within 28 days before screening, or while on study, is prohibited:

   • Systemic corticosteroids > prednisolone 10 mg or equivalent.
   • Physiologic doses of systemic steroid replacement or local (topical, nasal, or inhaled) steroid use. Limited doses of systemic steroids (e.g., in participants with exacerbations of reactive airway disease or to prevent intravenous (IV) contrast allergic reaction or anaphylaxis in participants who have known contrast allergies) are permitted.
   • Other investigational or approved therapies for mAPMR (excluding denosumab and bisphosphonates).

4. Received or plans to receive PAP-directed therapy at any time before screening, or while on study.

5. Received or plans to receive any live or live-attenuated vaccine within 4 weeks before the first dose of study drug or while on study. Inactivated or non-live vaccines (e.g., authorized or approved vaccines such as COVID-19, influenza, rabies, tetanus toxoid) are allowed if not administrated within 72 hours before or after KMV002 dosing.

6. Prior or anticipated radiation therapy, including: radiation for primary tumor within 4 weeks prior to screening, radiation or radionuclide therapy for metastasis within 4 weeks prior to screening (excluding palliative radiation for pain control), or anticipated need for such therapy (e.g., for imminent pathological fracture or spinal cord compression) while on study.

7. Unstable symptomatic ischemic heart disease, ongoing arrhythmias or New York Heart Association (NYHA) Class III or IV heart failure.

8. Prior cytotoxic chemotherapy within 3 months before screening is prohibited (for example, but not limited to, docetaxel, mitoxantrone, cabazitaxel). Received more than one chemotherapy regimens at any time before screening.

9. Treatment with any investigational vaccine within 2 years before screening or treatment with any other investigational product within 4 weeks before screening.

10. Had major surgery (e.g., requiring general anesthesia) within 4 weeks before screening or has not recovered from surgery. Must not have major surgery planned during the time the participant is receiving the study drug. Participants with recent or planned surgical procedures utilizing only local anesthesia may participate.

11. Malignancy diagnosis other than the disease under study within 2 years prior to the first dose of KMV002, except for squamous and basal cell carcinoma of the skin, non-muscle invasive bladder cancer, cervical intraepithelial neoplasia or any malignancy considered cured or has minimal risk of recurrence within 1 year of first dose of KMV002 (in the opinion of both the investigator and medical monitor).

12. Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%) or spinal cord compression.

13. Paget's disease of bone.

14. Active autoimmune diseases or history of autoimmune disease requiring systemic immunosuppressive therapy (including but not limited to corticosteroids >10 mg/day prednisone equivalent, methotrexate, azathioprine, anti-TNF agents, tocilizumab). Exceptions (allowed without systemic therapy): vitiligo, diabetes mellitus, and Hashimoto's thyroiditis on appropriate replacement therapy may be enrolled. Other autoimmune conditions that are clinically stable and do not require systemic immunosuppression may be considered on a case-by-case basis after discussion with the Sponsor.

15. History of significant local or systemic reactogenicity to any prior vaccine or to CpG ODN (e.g., anaphylaxis, respiratory difficulties, angioedema, injection site necrosis or ulceration).

16. Any serious underlying medical conditions or other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to understand the informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol specified assessments.