Trial of LAVA-1207 in Patients With Therapy Refractory Metastatic Castration Resistant Prostate Cancer (mCRPC) Resistant Prostate Cancer

Exclusion Criteria

• •Patients are excluded from the trial if any of the following criteria apply:
• •1. Other malignancies within the last 2 years except adequately treated carcinoma in situ, basal or squamous cell skin carcinoma.
• •2. Uncontrolled or severe intercurrent medical condition.
• •3. Positive serological testing for human immunodeficiency virus (HIV) antibody.
• •4. Positive serological hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) negative, and hepatitis C virus (HCV) antibody. Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative polymerase chain reaction (PCR) within 6 weeks prior to initial IMP administration. Those who are PCR positive will be excluded.
• •5. Patient has any active, uncontrolled, or suspected infection.
• •6. Known clinically relevant immunodeficiency disorders.
• •7. A significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect participation in this trial.
• •8. Unstable cardiovascular function defined as: (a) symptomatic ischemia, or (b) uncontrolled clinically significant conduction abnormalities (i.e. ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block is not excluded), or (c) congestive heart failure New York Heart Association Class ≥ 3, or (d) myocardial infarction within 3 months.
• •9. Previous treatment with antitumor therapies within 2 weeks prior to initial IMP for radiotherapy and androgen receptor targeted therapy/androgen biosynthesis inhibitor, and within 4 weeks for systemic chemotherapy or targeted immunotherapy.
• •10. Previous treatment with live or live attenuated vaccines within 2 weeks prior to initial IMP administration. New types of vaccines need to be evaluated as to their mode of action.
• •11. Treatment with other investigational agents in the 4 weeks prior to initial IMP administration.
• •12. Major surgery within 4 weeks prior to initial IMP administration.
• •13. Hypersensitivity to any of the excipients present in LAVA-1207 or IL-2 (if applicable).
• •14. Previous treatment with any systemic immunosuppressant within 4 weeks prior to initial IMP administration, with the exception of systemic corticosteroid use up to oral dose of 10 mg prednisone daily (or equivalent for other steroids).
• •15. Previous treatment with an aminobisphosphonate IV (e.g., ibandronate, pamidronate, zoledronate etc.) within 12 months prior to initial IMP.
• •16. Known ongoing drug and alcohol abuse in the opinion of the investigator.
• •Patients are excluded from the arm if any of the following criteria apply:
• •1. Other malignancies within the last 2 years except adequately treated carcinoma in situ, basal or squamous cell skin carcinoma.
• •2. Seropositive for and with evidence of active viral infection with hepatitis B virus (HBV). Patients who are HBsAg negative and HBV viral DNA negative are eligible. Patients who had HBV but have received an antiviral treatment and show non-detectable viral DNA for 6 months are eligible. Patients who are seropositive because of HBV vaccine are eligible.
• •3. Seropositive for and with active viral infection with hepatitis C virus (HCV). Patients who had HCV but have received an antiviral treatment and show no detectable HCV viral DNA for 6 months are eligible.
• •4. History of allogenic tissue or solid organ transplant.
• •5. Positive serological testing for HIV.
• •6. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• •7. Hypersensitivity to any of the excipients present in LAVA-1207.
• •8. Active infection requiring systemic therapy.
• •9. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• •10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• •11. Has an active autoimmune disease that has required systemic treatment in 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) is not considered a form of systemic treatment and is allowed.
• •12. Has received prior therapy with an anti-programmed cell death 1 (PD 1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune related AE (irAE).
• •13. A significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that in the opinion of the investigator would adversely affect participation in this trial.
• •14. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• •15. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to treatment. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs ≤Grade 2 requiring treatment or hormone replacement may be eligible. Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
• •16. Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis. Note: Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
• •17. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Administration of killed vaccines are allowed.
• •18. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• •19. Major surgery within 4 weeks prior to initial IMP administration.
• •20. Previous treatment with an aminobisphosphonate IV (e.g., ibandronate, pamidronate, zoledronate etc.) within 12 months prior to initial IMP.
• •21. Known ongoing drug and alcohol abuse in the opinion of the investigator.
• •22. Patients will be unlikely to tolerate or derive clinically meaningful benefit from other available therapy.
• •23. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• •24. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.