A Platform Study of Novel Immunotherapy Products in Participants With Previously Treated Unresectable or Metastatic Cutaneous Melanoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomized, Open-label, Multicenter, Multi-arm, Phase 1b/2 Platform Study to Evaluate Safety and Efficacy of Investigational Immunotherapies in Participants With Previously Treated Unresectable or Metastatic Melanoma

Conditions
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Unresectable Cutaneous Melanoma, Metastatic Cutaneous Melanoma

Intervention / Treatment
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* Combination Product: Sintilimab + IBI110


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults, age 18 years or older Histologically confirmed unresectable or metastatic cutaneous melanoma Documented radiological progression on prior treatment(s) that included an anti-PD-1/L1 agent Available tumor tissue OR be willing to provide a fresh tumor biopsy Presence of at least one measurable lesion as assessed by CT and/or MRI according to RECIST 1.1 Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 Adequate organ and bone marrow function Exclusion Criteria: Known hypersensitivity to monoclonal antibodies, any of the IPs, or excipients contained in these products Current anti-cancer therapy, other investigational treatment, or any participation in other interventional trials Prior exposure to any therapy that targets the same target as the product under investigation, except for PD-1/L1 Known symptomatic/active untreated central nervous system (CNS) metastasis Inadequate recovery from toxicity and/or complications attributable to any previous anti-cancer therapy Inadequate recovery from all recent surgeries At least 1-week from the time of minor surgery and at least 4 weeks from a major surgery Received a live vaccine within 30 days prior to randomization (or planned to receive a live attenuated vaccine during the study) History of HIV infection (positive HIV test, not on antiretroviral therapy, detectable viral load) Active hepatitis B (positive hepatitis B surface antigen test) or hepatitis C infection (positive hepatitis C antibody) Documented history or current diagnosis of clinically significant cardiac disease History of or present CNS disease unrelated to cancer, unless adequately treated with standard medical therapy Received solid organ or bone marrow transplantation History of non-infectious pneumonitis requiring corticosteroid therapy within 1 year prior to enrollment, or current presence of interstitial lung disease 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 Requiring long term systemic corticosteroids, except topical cortical steroids for intranasal inhalation or physiological dose Active gastrointestinal (GI) bleeding or GI perforation or fistula Serious active infection requiring intravenous (IV) antibiotics and/or hospitalization at study entry 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: An open-label platform study that will allow evaluation of multiple novel IPs. The study will include multiple treatment arms that can be added sequentially or in parallel. There will be a master protocol describing study design elements common to all treatment arms with treatment arms described in the appendices, added through amendments.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm 1<br>Sintilimab is a recombinant fully human anti-programmed cell death protein 1 (PD-1) monoclonal antibody, and IBI110 is a recombinant fully human anti-lymphocyte activation gene 3 (LAG3) monoclonal antibody. Sintilimab (IBI308) will be administered intravenously (IV) in combination with IBI110 administered intravenously (IV) every 3-weeks (Q3W). | Combination Product: Sintilimab + IBI110<br>* IBI110 infusion in combination with Sintilimab (IBI308) infusion will be given on a Q3W schedule<br>* Other names: Sintilimab (IBI308);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety, tolerability, and preliminary efficacy of novel immunotherapy IPs in participants with unresectable or metastatic melanoma that progressed while on prior treatment that included an anti-PD-1/L1 agent. (Selection Part) | Incidence and severity of Adverse Events (AEs) and laboratory abnormalities | Up to 28 months | 
| To evaluate the safety, tolerability, and preliminary efficacy of novel immunotherapy IPs in participants with unresectable or metastatic melanoma that progressed while on prior treatment that included an anti-PD-1/L1 agent. (Selection Part) | Incidence of dose-limiting toxicities (DLTs) [only applicable for safety run-in portion] | Day 1 to Day 42 | 
| To identify novel immunotherapy IPs to progress into the expansion part (Selection Part) | Overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Up to 2 years | 
| To evaluate the antitumor efficacy of immunotherapy in partcipants with unresectable or metastatic melanoma that progressed while on prior treatment(s) that included an anti-PD-1/L1 agent. (Expansion Part) | ORR by RECIST 1.1 | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the preliminary anti-tumor efficacy by assessing additional endpoints of novel immunotherapy IPs (Selection Part) | Duration of response (DOR) by RECIST 1.1 | Up to 4 years | 
| To evaluate the preliminary anti-tumor efficacy by assessing additional endpoints of novel immunotherapy IPs (Selection Part) | Time to Response (TTR) by RECIST 1.1 | Up to 2 years | 
| To evaluate the preliminary anti-tumor efficacy by assessing additional endpoints of novel immunotherapy IPs (Selection Part) | Disease control rate (DCR) by RECIST 1.1 | Up to 2 years | 
| To evaluate the preliminary anti-tumor efficacy by assessing additional endpoints of novel immunotherapy IPs (Selection Part) | Progression-free survival (PFS) by RECIST 1.1 | Up to 4 years | 
| To evaluate the preliminary anti-tumor efficacy by assessing additional endpoints of novel immunotherapy IPs (Selection Part) | Overall survival (OS) | Up to 4 years | 
| To characterize the pharmacokinetic (PK) profile and immunogenicity (Selection, Expansion Part) | Pharmacokinetic parameters including, but not limited to area under the concentration -time curve over dosing interval (AUCtau), Maximum observed plasma concentration at steady state (Cmax,ss), and trough plasma concentration at steady state (Ctrough,ss) | Up to 25 months | 
| To characterize the pharmacokinetic (PK) profile and immunogenicity (Selection, Expansion Part) | Prevalence and incidence of anti-product antibodies (ADA, Nab) | Up to 25 months | 
| To evaluate anti-tumor efficacy by assessing additional endpoints by RECIST 1.1 (Expansion Part) | Duration of response (DOR) by RECIST 1.1 | Up to 4 years | 
| To evaluate anti-tumor efficacy by assessing additional endpoints by RECIST 1.1 (Expansion Part) | Time to Response (TTR) by RECIST 1.1 | Up to 2 years | 
| To evaluate anti-tumor efficacy by assessing additional endpoints by RECIST 1.1 (Expansion Part) | Disease control rate (DCR) by RECIST 1.1 | Up to 2 years | 
| To evaluate anti-tumor efficacy by assessing additional endpoints by RECIST 1.1 (Expansion Part) | Progression-free survival (PFS) by RECIST 1.1 | Up to 4 years | 
| To evaluate anti-tumor efficacy by assessing additional endpoints by RECIST 1.1 (Expansion Part) | Overall survival (OS) | Up to 4 years | 
| To further evaluate the safety and tolerability of novel immunotherapy IPs (Expansion Part) | Incidence and severity of AEs and laboratory abnormalities | Up to 28 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoplasms, Melanoma, Malignant Melanoma