A Study of SEA-CD40 Given With Other Drugs in Cancers

Open to people ages 18 years and up

• Histologically or cytologically confirmed unresectable malignancy defined as one of the following:
• Cohort 1: Relapsed and/or refractory metastatic melanoma
• Uveal/ocular melanoma is excluded
• Must have progressed on treatment with an anti-PD-(L)1 mAb. PD-(L)1 treatment progression is defined as meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-(L)1 mAb
• Has demonstrated disease progression after PD-(L)1 as defined by RECIST v1.1.
• Progressive disease has been documented within 12 weeks from the last dose of anti- PD-(L)1 mAb
• Last dose of anti-PD-(L)1 must have been within 90 days prior to enrollment
• Participants with a targetable BRAF mutation must have been treated with, been intolerant of, or declined treatment with BRAF/MEK targeted therapy prior to study entry
• Cohort 2: Metastatic uveal melanoma
• Must not have received prior treatment for advanced or metastatic disease except for prior adjuvant/neoadjuvant immunotherapy
• No prior liver-directed therapy
• Cohort 3: Metastatic PD-(L)1-naive melanoma
• Uveal/ocular melanoma is excluded
• Must not have received prior treatment for advanced or metastatic disease except for prior adjuvant/neoadjuvant immunotherapy.
• For participants with a targetable BRAF mutation, prior BRAF/MEK targeted therapy is allowed if completed 4 weeks prior to first dose of study treatment.
• Cohorts 4 and 5: Non-squamous NSCLC
• Participants must have stage IV disease per AJCC 8th edition
• No known driver mutations/alterations mutation for which targeted therapy is available
• Must have non-squamous histology.
• No prior therapy for metastatic disease
• No prior treatment with anti-PD-(L)1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms
• Able to provide archival tumor tissue from locations not radiated prior to biopsy. If archival tumor sample is not available a fresh baseline biopsy is required.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Measurable disease per RECIST v1.1 at baseline

• History of another malignancy within 3 years of first dose of study drug
• Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Previous exposure to CD40-targeted therapy
• Currently on chronic systemic steroids in excess of physiologic replacement
• Has had an allogeneic tissue/solid organ transplant.
• History of autoimmune disease that has required systemic treatment in the past 2 years