Metastatic Cutaneous Melanoma, Unresectable Cutaneous Melanoma
Conditions
Keywords
Neoplasms, Melanoma, Malignant Melanoma
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.
Interventions
COMBINATION_PRODUCTSintilimab + IBI110
IBI110 infusion in combination with Sintilimab (IBI308) infusion will be given on a Q3W schedule
Sponsors
Innovent Biologics (USA), Inc.
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to 28 months | Incidence and severity of Adverse Events (AEs) and laboratory abnormalities |
| 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
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the preliminary anti-tumor efficacy by assessing additional endpoints of novel immunotherapy IPs (Selection Part) | Up to 4 years | Duration of response (DOR) by RECIST 1.1 |
| 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 |
| To characterize the pharmacokinetic (PK) profile and immunogenicity (Selection, Expansion Part) | Up to 25 months | 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) |
| To evaluate anti-tumor efficacy by assessing additional endpoints by RECIST 1.1 (Expansion Part) | Up to 4 years | Duration of response (DOR) by RECIST 1.1 |
Countries
Australia, France, Germany, Spain, Switzerland, United Kingdom, United States
Outcome results
None listed