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

Inclusion Criteria:

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

Exclusion Criteria:

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