Safety and Efficacy of Anti-CD47, ALX148 in Combination With Liposomal Doxorubicin and Pembrolizumab in Recurrent Platinum-resistant Ovarian Cancer

Inclusion Criteria

• •1. Participants must have recurrent epithelial ovarian cancer.
• •7. Patients having received prior therapy with PD1, PDL1, CTLA4 inhibitors, CD47 or SIRP1- α inhibitors or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137), or other immunotherapeutic agents.
• •8. Prior therapy with PLD. Patients who received PLD in combination with platinum in platinum sensitive setting are allowed if they had initial objective complete response and PLD-platinum free interval of 6 months or more.
• •9. Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• •10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing ≥ 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 active autoimmune disease that has required systemic treatment in the past 2 years (with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• •12. Patients currently on immunosuppressive therapy except: intra-nasal, inhaled, topical or local steroid injections, steroids as premedication, systemic corticosteroids ≤10 mg/day of prednisone or equivalent
• •13. Patients who are pregnant or breast feeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• •14. Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis ((non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease), pulmonary fibrosis.
• •15. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• •17. Prior organ transplantation including allogenic stem-cell transplantation.
• •18. Active infection requiring intravenous systemic therapy. Oral antibiotic therapy is allowed.
• •19. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
• •Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority or treating physician per standard of care except patients with a known history of Hepatitis B not on a stable dose of antiviral therapy, with HBV viral load below the limit of quantification. HCV viral load below the limit of quantification.
• •20. History of infection with (screening tests not required) human immunodeficiency virus; except following situation:
• •a. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment are eligible for this trial.
• •21. Received live or live-attenuated vaccine within 4 weeks of the first dose of treatment and while on trials is prohibited except for administration of inactivated vaccines. Influzena and COVID vaccinations are permissible.
• •22. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5 Grade ≥ 3).
• •23. Persistent toxicity related to prior therapy (NCI CTCAE v. 5 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
• •24. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• •25. A WOCBP who has a positive urine pregnancy test within 72 hours prior to \[randomization/allocation\] (see Appendix IV). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.