a platform study of novel immunotherapy products in participants with previously treated unresectable or metastatic cutaneous melanoma

Conditions: Unresectable Cutaneous Melanoma; Metastatic Cutaneous Melanoma

Summary: this is a platform study evaluating the safety and efficacy of multiple novel investigational products (ips) that target unresectable or metastatic cutaneous melanoma in participants who have failed standard treatment.

this is a phase 1b/2, randomized, open label, multicenter, platform study evaluating the safety and efficacy of multiple novel investigational products (ips) that target mechanisms implicated in resistance to immunotherapy in participants with unresectable or metastatic cutaneous melanoma who have resistance to anti-pd-1/l1 agents. this study will include multiple treatment arms that can be added sequentially or in parallel. each arm consists of a selection and expansion part. the selection part is used for evaluation of safety and preliminary efficacy in each arm. the selection part may also include a safety run-in portion for preliminary safety evaluation and dose confirmation prior to proceeding. if the criteria for safety and preliminary efficacy are met, the arm will open for additional enrollment in an expansion phase.

Eligibility criteria:
inclusion criteria: 1. adults, age 18 years or older 2. histologically confirmed unresectable or metastatic cutaneous melanoma 3. documented radiological progression on prior treatment(s) that included an anti-pd-1/l1 agent 4. available tumor tissue or be willing to provide a fresh tumor biopsy 5. presence of at least one measurable lesion as assessed by ct and/or mri according to recist 1.1 6. eastern cooperative oncology group performance status (ecog ps) of 0-1 7. adequate organ and bone marrow function exclusion criteria: 1. known hypersensitivity to monoclonal antibodies, any of the ips, or excipients contained in these products 2. current anti-cancer therapy, other investigational treatment, or any participation in other interventional trials 3. prior exposure to any therapy that targets the same target as the product under investigation, except for pd-1/l1 4. known symptomatic/active untreated central nervous system (cns) metastasis 5. inadequate recovery from toxicity and/or complications attributable to any previous anti-cancer therapy 6. inadequate recovery from all recent surgeries 7. at least 1-week from the time of minor surgery and at least 4 weeks from a major surgery 8. received a live vaccine within 30 days prior to randomization (or planned to receive a live attenuated vaccine during the study) 9. history of hiv infection (positive hiv test, not on antiretroviral therapy, detectable viral load) 10. active hepatitis b (positive hepatitis b surface antigen test) or hepatitis c infection (positive hepatitis c antibody) 11. documented history or current diagnosis of clinically significant cardiac disease 12. history of or present cns disease unrelated to cancer, unless adequately treated with standard medical therapy 13. received solid organ or bone marrow transplantation 14. history of non-infectious pneumonitis requiring corticosteroid therapy within 1 year prior to enrollment, or current presence of interstitial lung disease 15. active or previously documented autoimmune disease including but not limited to inflammatory bowel disease, diverticulitis, celiac disease, systemic lupus erythematosus, wegener syndrome, multiple sclerosis, and vasculitis 16. requiring long term systemic corticosteroids, except topical cortical steroids for intranasal inhalation or physiological dose 17. active gastrointestinal (gi) bleeding or gi perforation or fistula 18. serious active infection requiring intravenous (iv) antibiotics and/or hospitalization at study entry 19. pregnant or lactating women or women who intend to get pregnant or lactate during the study and up to 120 days after the end of treatment

Keywords: neoplasms melanoma malignant melanoma