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

This clinical trial (study) is for patients with melanoma or non-small cell lung cancer (NSCLC). This clinical trial uses an investigational drug, which means the Food and Drug Administration (FDA) hasn’t approved it for sale in the United States and it must be tested to see if it is a safe and effective treatment for the disease or condition being studied. This drug is called SEA-CD40.

This clinical trial also uses pembrolizumab. The brand name for pembrolizumab is KEYTRUDA®. It’s a kind of anti-cancer drug called an immune checkpoint inhibitor (CPI). Pembrolizumab is approved by the FDA to treat several types of cancer, including melanoma and NSCLC. This clinical trial also uses pemetrexed and carboplatin. These chemotherapy drugs are approved by the FDA for treating various cancers.

If you have melanoma, we will give you SEA-CD40 and pembrolizumab in this study. If you have NSCLC, we will give you SEA-CD40, pembrolizumab, pemetrexed, and carboplatin in this study.

We are studying SEA-CD40 together with pembrolizumab to find out if they work to treat melanoma. We are also studying SEA-CD40 together with pembrolizumab, pemetrexed, and carboplatin to find out if they work to treat NSCLC. We also want to find out what the side effects are. A side effect is anything the drug does to your body besides treating your disease. If you have side effects, your doctor may prescribe or give you medicine to help you with your symptoms. Learning about the side effects of these drugs and how they work will help us understand if these drugs work for melanoma or NSCLC.

If you agree to participate in this study, your participation may last up to 2 years and you will be asked to complete 10 or more study visits.

In order to participate you must meet the following criteria:

• Group 1: Relapsed and/or refractory metastatic melanoma
  • Uveal/ocular melanoma is excluded
  • Must have progressed on treatment with an anti-PD-(L)1 mAb.
• Group 2: Metastatic uveal melanoma
  • Must not have received prior treatment for advanced or metastatic disease except for prior adjuvant/neoadjuvant immunotherapy
  • No prior regional, liver-directed therapy
• Group 3: Metastatic PD-(L)1-naïve melanoma
  • Uveal/ocular melanoma is excluded
  • Must not have received prior treatment for advanced or metastatic disease except for prior adjuvant/neoadjuvant immunotherapy.
  • Participants with BRAF mutation, prior BRAF/MEK targeted therapy is allowed if completed 4 weeks prior to first dose of study treatment.
• Groups 4 and 5: Non-squamous NSCLC
  • Participants must have stage IV disease
  • No known driver mutations/alterations mutation for which targeted therapy is available
  • 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

You will be excluded from the study if any of the following criteria apply to you:

• 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

This is a partial list of inclusion and exclusion criteria.