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

Seagen

Status and phase: Active, not recruiting; Phase 2

Conditions: Carcinoma, Non-Small- Cell Lung; Melanoma

Treatments: Drug: SEA-CD40; Drug: carboplatin; Drug: pemetrexed; Drug: pembrolizumab (KEYTRUDA®)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04993677

KEYNOTE-C86 (Other Identifier)

SGNS40-002

Details and patient eligibility

About

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.

Enrollment: 77 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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77 participants in 2 patient groups

Melanoma Arm

Experimental group

Description:

SEA-CD40 + pembrolizumab

Treatment:

Drug: pembrolizumab (KEYTRUDA®)

Drug: SEA-CD40

NSCLC Arm

Experimental group

Description:

SEA-CD40 + pembrolizumab + pemetrexed + carboplatin

Treatment:

Drug: pembrolizumab (KEYTRUDA®)

Drug: pemetrexed

Drug: carboplatin

Drug: SEA-CD40