ALPN-202 With PD-1 Inhibition in Advanced Malignancies

Exclusion Criteria

• •Any history of ≥ Grade 3 immune-related adverse event (irAE) requiring discontinuation from treatment or any history of a cardiovascular irAE
• •Active or prior pneumonitis or interstitial lung disease
• •Presence of any active central nervous system metastases
• •Prior organ allograft or allogeneic hematopoietic stem cell transplantation
• •Any other serious or uncontrolled health condition, which, in the opinion of the Investigator, would place the subject at undue risk from the study, impair the ability of the subject to receive protocol specified therapy, or interfere with the interpretation of study results.
• •Receipt of any protocol-restricted therapy within the timeframes indicated:
• •1. Checkpoint inhibitors, including PD-(L)1 (e.g., pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab), CTLA-4 (e.g., ipilimumab, tremelimumab), and Lag-3 (e.g., relatlimab), costimulatory agonists (including but not limited to CD28, CD134 (OX40), CD137 (4-1BB)): 3 months (135 days for atezolizumab)
• •2. Chemotherapy, small molecule anticancer agents (e.g., kinase inhibitors), or radiation: 2 weeks
• •3. Other monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, antibody-like drugs, cytokines, cell therapies, or radioimmunoconjugates: 4 weeks
• •Any active, known, or suspected autoimmune disease
• •Systemic treatment with corticosteroids (\> 10 mg/day prednisone) or other immunosuppressive medication
• •Any second malignancy active within the previous 3 years
• •Active infection requiring therapy at the time of the first dose of ALPN-202.
• •Known seropositivity for or active infection by human immunodeficiency virus, hepatitis B or C, or or Severe Acute Respiratory Syndrome Coronavirus 2.
• •Known allergies, hypersensitivity, or intolerance to ALPN-202 or excipients in the drug product formulation.
• •History of Grade 4 infusion-related, anaphylactic or allergic reaction to any previous Fc-based protein therapy.
• •Any serious or uncontrolled cardiovascular condition, including but not limited to:
• •1. Any history of myocarditis of any etiology
• •2. History of New York Heart Association Class III or IV congestive heart failure, myocardial infarction, unstable angina, cerebrovascular accident, cardiac hospitalization, or other acute uncontrolled heart disease within 6 months of scheduled C1D1
• •3. Left ventricular ejection fraction \< 45% on screening echocardiogram
• •4. Any clinically significant findings on screening EKG such as atrial or ventricular arrythmia (other than sinus tachycardia) or AV conduction abnormality such as left bundle branch block (such subjects may be enrolled after cardiology clearance and Medical Monitor approval)
• •Has received prior radiotherapy within 2 weeks of start of study treatment, or have had a history of radiation pneumonitis