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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Cutaneous Melanoma; Unresectable Cutaneous Melanoma
• Intervention / Treatment: Combination product: Sintilimab + IBI110

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Victoria Hospital
• France
  • Lyon, France, 69002
    • Hospices Civil De Lyon Nord - Centre Hospitalier Lyon Sud - Dermatologie
  • Paris, France, 75010
    • Hospital Saint Louis
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus
  • Essen, Germany, 45147
    • Universitatsklinikum Essen
• Spain
  • Barcelona, Spain, 8916
    • Institut Catala d'Oncologia Hospital Universitari Germans Trials I Pujol, Barcelona
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia, Cordoba
• Switzerland
  • Zürich, Switzerland, 8091
    • Universitaets Spital Zurich
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust (Oxford)
  • Preston, United Kingdom, PR2 9HT
    • Lancashire Teaching Hospitals (Preston)
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm 1; 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; IBI110 infusion in combination with Sintilimab (IBI308) infusion will be given on a Q3W schedule; Other Names: Sintilimab (IBI308)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Collaborators: Innovent Biologics (USA), Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2022
• Primary Completion (Anticipated): June 30, 2027
• Study Completion (Anticipated): December 31, 2027

Study Registration Dates

• First Submitted: October 5, 2022
• First Submitted That Met QC Criteria: October 5, 2022
• First Posted (Actual): October 7, 2022

Study Record Updates

• Last Update Posted (Actual): November 18, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Neoplasms; Melanoma; Malignant Melanoma
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Skin Neoplasms
• Other Study ID Numbers: PLATFORM201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No