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

This trial is being done to see if an experimental drug (SEA-CD40) works when it's given with other cancer drugs to treat some types of cancer. It will also study side effects from the drug.

There are 2 parts in this trial. In one part, participants have melanoma that has come back after treatment or can't be removed by surgery. Participants in this part will get SEA-CD40 and pembrolizumab. In the other part, participants have non-small cell lung cancer (NSCLC) that has spread through their body. These participants will get SEA-CD40, pembrolizumab, carboplatin, and pemetrexed.


Eligibility Criteria:
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