Clinical Trial Finder

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

Arms

Experimental: Melanoma Arm

SEA-CD40 + pembrolizumab

Experimental: NSCLC Arm

SEA-CD40 + pembrolizumab + pemetrexed + carboplatin

Interventions

Drug: - SEA-CD40

Given into the vein (IV; intravenously); schedule is cohort-specific

Drug: - pembrolizumab (KEYTRUDA®)

Given by IV; schedule is cohort-specific.

Drug: - pemetrexed

Given by IV on Day 1 of each 21-day cycle.

Drug: - carboplatin

Given by IV on Day 1 of Cycles 1-4. Each cycle will be 21 days long.