ALT-100 Monoclonal Antibody (mAb) in Bone-Predominant Metastatic Androgen Pathway Modulation Resistant (APMR) Prostate Cancer -- The ALTAR-100 Trial

Prior treatment

• Impending skeletal-related event requiring immediate radiotherapy or surgical intervention or untreated spinal cord compression
• Chemotherapy, investigational therapy, or any systemic anticancer therapy other than ADT within 4 weeks or 5 half-lives of C1D1, whichever is shorter
• Prior exposure to any extracellular nicotinamide phosphoribosyltransferase (eNAMPT)-directed or toll-like receptor 4 (TLR4)-directed therapeutic agent.
• Known hypersensitivity to a monoclonal antibody, or prior grade ≥3 infusion-related reaction to a biologic
• Administration of a vaccine containing live virus within 30 days prior to the first dose of trial treatment. Note: Most flu vaccines are killed viruses, with the exception of the intra-nasal vainer (Flu-Mist) which is an attenuated live virus and therefore prohibited for 30 days prior to first dose.

Other illness

• Visceral metastases, including liver, lung, adrenal, brain or peritoneal disease. Lymph node involvement is permitted
• Active infection requiring systemic therapy at C1D1
• Known HIV infection, or known active hepatitis B or hepatitis C, that is uncontrolled or requires a change in therapy. Testing is not required at screening
• Cardiovascular or thromboembolic disease that, in the investigator's judgment, is uncontrolled or would place the patient at undue risk on study
• Chronic systemic immunosuppressive therapy at doses that in the investigator's judgement would place the patient at undue infection risk
• Another malignancy requiring active treatment, except non-melanoma skin cancer or adequately treated in situ disease
• Any condition that in the investigator's judgement would compromise safety or protocol compliance
• Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

Lab values

• External beam radiotherapy to a bone lesion within 4 weeks of C1D1 or radiotherapy planned during the DLT window of 30 days after first dose of ALT-100.
• Active osteonecrosis of the jaw, or invasive dental procedure planned during the DLT window of 30 days after first dose of ALT-100

Other

• Known pure small cell or neuroendocrine prostate carcinoma
• Radium-223 within 6 months of C1D1

• Male, age ≥ 18 years
• Prostate cancer, histologically confirmed or presumed on the basis of clinical, biochemical, and/or radiographic findings.
• Metastatic disease confined to bone and lymph nodes, with bone metastases predominant, documented on conventional imaging (CT/MRI and bone scan). Measurable soft tissue disease is not required.
• Androgen pathway modulation-resistant (APMR) disease per Prostate Cancer Working Group 4 (PCWG4) with progression on at least one prior androgen receptor pathway inhibitor documented as any of the following:
  • Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL,
  • Soft tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions,
  • For PSMA-PET: Two new PSMA-avid lesions, or
  • Progression of bone disease defined by the appearance of ≥2 new bone lesions on bone scan per PCWG4 criteria
• Ongoing androgen deprivation therapy (ADT) with a Gonadotropin-releasing hormone analogue, or prior bilateral orchiectomy, with serum testosterone <50 ng/dL
• ECOG performance status 0-2
• Life expectancy ≥6 months
• Adequate organ and marrow function defined as:
  • ANC ≥1,500/µL
  • Platelets ≥100,00/µL
  • Hemoglobin ≥9.0 g/dL without transfusion within 14 days
  • Total bilirubin ≤1.5 x ULN (≤ 3 x ULN for Gilbert's)
  • AST and ALT ≤3 x ULN
  • Creatinine clearance ≥30 mL/min
• Concurrent bone-modifying agent (including, but not limited to denosumab or bisphosphonates such as zoledronic acid or pamidronate), permitted but not required. If receiving one, it must have been at a stable dose and scheduled for ≥8 weeks before C1D1.
• Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures.
• Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 6 months following the last dose of study drug.