a study of sea-cd40 given with other drugs in cancers

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

Summary: 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

Keywords: relapsed melanoma refractory melanoma metastatic uveal melanoma metastatic pd-(l)1-naïve melanoma non-squamous nsclc nsclc non-small cell lung cancer seattle genetics