A Platform Study of Novel Immunotherapy Products in Participants With Previously Treated Unresectable or Metastatic Cutaneous Melanoma
- Conditions
- Unresectable Cutaneous MelanomaMetastatic Cutaneous Melanoma
- Interventions
- Combination Product: Sintilimab + IBI110
- Registration Number
- NCT05572463
- Lead Sponsor
- Innovent Biologics (Suzhou) Co. Ltd.
- Brief 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Treatment Arm 1 Sintilimab + IBI110 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).
- Primary Outcome Measures
Name Time Method 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) Day 1 to Day 42 Incidence of dose-limiting toxicities (DLTs) \[only applicable for safety run-in portion\]
To identify novel immunotherapy IPs to progress into the expansion part (Selection Part) Up to 2 years Overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
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) Up to 2 years ORR by RECIST 1.1
- Secondary Outcome Measures
Name Time Method To evaluate the preliminary anti-tumor efficacy by assessing additional endpoints of novel immunotherapy IPs (Selection Part) Up to 4 years Overall survival (OS)
To characterize the pharmacokinetic (PK) profile and immunogenicity (Selection, Expansion Part) Up to 25 months Prevalence and incidence of anti-product antibodies (ADA, Nab)
To evaluate anti-tumor efficacy by assessing additional endpoints by RECIST 1.1 (Expansion Part) Up to 4 years Overall survival (OS)
To further evaluate the safety and tolerability of novel immunotherapy IPs (Expansion Part) Up to 28 months Incidence and severity of AEs and laboratory abnormalities
Trial Locations
- Locations (13)
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of California San Francisco Medical Center
🇺🇸San Francisco, California, United States
Princess Victoria Hospital
🇦🇺Woolloongabba, Queensland, Australia
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Universitatsklinikum Carl Gustav Carus
🇩🇪Dresden, Germany
Universitatsklinikum Essen
🇩🇪Essen, Germany
Cambridge University Hospitals NHS Foundation Trust (Oxford)
🇬🇧Cambridge, United Kingdom
Lancashire Teaching Hospitals (Preston)
🇬🇧Preston, United Kingdom
Hospital Saint Louis
🇫🇷Paris, France
Institut Catala d'Oncologia Hospital Universitari Germans Trials I Pujol, Barcelona
🇪🇸Barcelona, Spain
Hospices Civil De Lyon Nord - Centre Hospitalier Lyon Sud - Dermatologie
🇫🇷Lyon, France
Hospital Universitario Reina Sofia, Cordoba
🇪🇸Córdoba, Spain
Universitaets Spital Zurich
🇨ðŸ‡Zürich, Switzerland