An Open-label Study of ALPN-202 in Subjects With Advanced Malignancies

Key Inclusion Criteria:

1. Adult 18 to 75 years old at screening
2. Pathologically-confirmed, locally advanced or metastatic unresectable solid tumor of an acceptable histology

   Part A (Dose Escalation)
   1. that is refractory or resistant to standard therapy, including checkpoint inhibitor(s) if approved
   2. or for which standard or curative therapy is not available

   Part B (Dose Expansion)
   1. metastatic cutaneous melanoma
   2. PD-L1-positive cancers (other than cutaneous melanoma or renal cell carcinoma)
   3. metastatic renal cell carcinoma
3. Protocol-defined measurable disease
4. Available tumor biopsy representative of current disease
5. ECOG performance status grade 0-2
6. Life expectancy of ≥ 3 months
7. Recovery to ≤ Grade 1 for any non-laboratory toxicity resulting from previous anticancer therapy prior to first dose of ALPN-202 (except alopecia, hearing loss, ≤ Grade 2 neuropathy or endocrinopathy managed with replacement therapy)
8. Adequate baseline hematologic, renal, and hepatic function

Key Exclusion Criteria:

1. History of ≥ Grade 3 immune-related adverse event leading to treatment discontinuation
2. Active or prior pneumonitis or interstitial lung disease
3. Presence of any active central nervous system metastases
4. Prior organ allograft or allogeneic hematopoietic stem cell transplantation
5. Any 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.
6. Receipt of any protocol-restricted therapy within the timeframes indicated:

   1. PD-L1 inhibitors: 5 half-lives (e.g., atezolizumab, 135 days; avelumab, 31 days; durvalumab, 85 days)
   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
7. Any active, known, or suspected autoimmune disease
8. Systemic treatment with corticosteroids (\> 10 mg/day prednisone) or other immunosuppressive medication
9. Any second malignancy active within the previous 3 years
10. Active infection requiring therapy at the time of the first dose of ALPN-202.
11. Known seropositivity for or active infection by human immunodeficiency virus, hepatitis B or C.
12. Known allergies, hypersensitivity, or intolerance to ALPN-202 or excipients in the drug product formulation.
13. History of Grade 4 infusion-related, anaphylactic or allergic reaction to any previous Fc-based protein therapy.