PD-1 Antibody Therapy + Infliximab for Metastatic Melanoma

NCT05034536 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-077
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to test the safety and effectiveness of the investigational combination of anti-Programmed Death (PD)-1 antibody therapy with or without LAG-3 inhibition (pembrolizumab or nivolumab+relatlimab) and infliximab in treating metastatic melanoma.

Conditions

Metastatic Melanoma

Keywords

Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• Incidence of immune-related adverse events (irAE) in patients treated with anti-PD-1 plus infliximab compared to pembrolizumab plus placebo

  Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  12 weeks

Secondary Outcomes (9)

• Incidence of severe immune-related adverse events (irAEs) (grade 3-5) in patients treated with anti-PD-1 antibody plus infliximab compared to anti-PD-1 antibody plus placebo

  12 weeks up to 2 years

• Incidence of anti-PD-1 antibody cessation due to immune-related adverse events (irAEs)

  12 weeks up to 2 years

• Incidence of clinically apparent infections in patients treated with anti-PD-1 antibody plus infliximab compared to anti-PD-1 antibody plus placebo

  12 weeks up to 2 years

• Overall survival rate of patients receiving combination anti-PD-1 antibody/infliximab compared with anti-PD-1 antibody/placebo

  Time from randomization (or registration) to death due to any cause, or censored at date last known alive up to 2 years

• Progression free survival rate of patients receiving combination anti-PD-1 antibody /infliximab compared with anti-PD-1 antibody/placebo

  Time from randomization (or registration) to the earlier of progression or death due to any cause up to 2 years.

Study Arms (2)

Anti-PD-1 therapy + Infliximab

EXPERIMENTAL

Participants will be randomly assigned to receive physician's choice of anti-PD-1 therapy (pembrolizumab or nivolumab+relatlimab) and infliximab. * Pembrolizumab will be administered every 3 weeks for up to 2 years * Nivolumab+relatlimab will be administered every 4 weeks for up to 2 years * Infliximab will be administered on weeks 0, 2, and 6 (+/- 3 days) for a total of 3 doses

Drug: Pembrolizumab; Drug: Infliximab; Drug: Relatlimab; Drug: Nivolumab

Anti-PD-1 therapy + Placebo

EXPERIMENTAL

Participants will be randomly assigned to receive physician's choice of anti-PD-1 therapy (pembrolizumab or nivolumab+relatlimab) and placebo. * Pembrolizumab will be administered every 3 weeks for up to 2 years * Nivolumab+relatlimab will be administered every 4 weeks for up to 2 years * Placebo. will be administered on weeks 0, 2, and 6 (+/- 3 days) for a total of 3 doses

Drug: Pembrolizumab; Drug: Placebo; Drug: Relatlimab; Drug: Nivolumab

Interventions

Pembrolizumab DRUG

Intravenous infusion

Also known as: Keytruda

Anti-PD-1 therapy + Infliximab; Anti-PD-1 therapy + Placebo

Infliximab DRUG

Intravenous infusion

Also known as: AVSOLA, Ixifi, Remicade, Renflexis

Anti-PD-1 therapy + Infliximab

Placebo DRUG

Intravenous infusion

Anti-PD-1 therapy + Placebo

Relatlimab DRUG

Intravenous infusion

Anti-PD-1 therapy + Infliximab; Anti-PD-1 therapy + Placebo

Nivolumab DRUG

Intravenous infusion

Anti-PD-1 therapy + Infliximab; Anti-PD-1 therapy + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years
• Participants must have histologically confirmed Stage III unresectable or Stage IV metastatic melanoma
• Patients should be treatment naïve and eligible for treatment with anti-PD-1 or anti-PD-1/LAG3 as a first line therapy (as selected by their treating physician)
• Patients previously treated for melanoma with surgical resection alone who present with recurrent Stage III unresectable or Stage IV metastatic melanoma are eligible for enrollment
• Patients who were previously treated with systemic neo-adjuvant or adjuvant anti-PD-1 therapy more than 6 months prior to study enrollment will be eligible. There are no restrictions to the use of prior BRAF targeted therapy.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10 mm with spiral CT scan
• Diagnostic imaging studies such as MRIs and CT scans must be performed within 30 days of the date of registration
• Participants must have normal organ and marrow function as defined below:
• Leukocytes (WBC) \> 3,000/uL
• Absolute neutrophil count \> 1,500uL
• Platelets \> 100,000/uL
• Total bilirubin \< 1.5 X institutional upper limits of normal; total bilirubin \> 1.5X above institutional upper limits of normal will be allowed if direct bilirubin is within normal limits or if patients has a documented history of Gilbert's disease
• AST (SGOT)/ALT (SGPT) \< 2.5 X institutional upper limit of normal and ≤5 ULN for patients with liver metastases
• Baseline laboratory measurements must be documented from tests within 14 days of the date of registration
• ECOG performance status ≤ 1 (see Appendix A)

You may not qualify if:

• Patients with ocular or mucosal melanoma
• Participants previously treated with anti-PD1/PDL1/CTLA-4 monoclonal antibodies for metastatic or unresectable disease
• Patients who are receiving other anti-neoplastic agents
• Symptomatic or untreated leptomeningeal disease
• Patients carrying a diagnosis of immunodeficiency or receiving systemic steroid therapy (prednisone or equivalent \> 10 mg/day) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Corticosteroids to prevent contrast reactions is allowable
• Patients with active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Prior history of inflammatory bowel disease, microscopic colitis or segmental colitis associated with diverticulosis
• Breastfeeding and pregnant women are excluded from this study since all anti-PD-1 drugs are class D agents with the potential for teratogenic or abortifacient effects.
• Uncontrolled intercurrent illness including, but not limited to:
• A. Ongoing or active infection
• B. Edema \> Grade 1
• C. Documented myocardial infarction or unstable/uncontrolled cardiac disease (eg, unstable angina, severe arrhythmias, congestive heart failure \[New York Heart Association (NYHA) \> Class II\]) within 6 months of study entry
• D. Arterial thrombosis or vascular ischemic events, such as transient ischemic attack, cerebral infarction, within 6 months prior to study entry
• E. Serious or non-healing wound
• F. History of any medical condition including cardiovascular disease or chronic obstructive pulmonary disease (COPD), that in the opinion of the investigator, may increase the risks associated with study participation or study treatments or may interfere with the conduct of the study or interpretation of study results

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Massachusetts Institute of Technology: collaborator

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; Infliximab; relatlimab; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized

Study Officials

• Ryan Sullivan, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 29, 2021
• First Posted: September 5, 2021
• Study Start: February 7, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)