Nivolumab Plus Relatlimab or Ipilimumab in Metastatic Melanoma Stratified by MHC-II Expression

NCT03724968 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: VICC MEL 18114NCI-2018-02469
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, non-randomized two arm Phase 2 study of intravenous nivolumab plus intravenous ipilimumab or intravenous relatlimab in patients with metastatic melanoma stratified by MHC-II expression.

Conditions

Metastatic Melanoma; Advanced Melanoma; Metastatic Melanoma Stratified by MHC-II Expression

Outcome Measures

Primary Outcomes (1)

• Change in Activated GZMB+ CD8+T-cell Density Intratumorally, of Two Immunotherapy Regimens

  Approximately 16 months

Secondary Outcomes (4)

• Response Rate

  Approximately 16 months

• Median Progression Free Survival

  Approximately 16 months

• Median Overall Survival

  Approximately 16 months

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 5.0

  Up to 30 days from last dose of drugs (average of 13 cycles)

Study Arms (2)

Arm A

EXPERIMENTAL

Nivolumab and Relatlimab

Drug: Nivolumab; Drug: Relatlimab

Arm B

EXPERIMENTAL

Nivolumab and Ipilimumab

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Nivolumab will be given by vein on day 1 of each cycle.

Arm A; Arm B

Relatlimab DRUG

Relatlimab will be given by vein on day 1 of each 28-day cycle

Arm A

Ipilimumab DRUG

Ipilimumab will be given by vein on day 1 during cycles 1-4 (cycles are 21 days).

Arm B

Eligibility Criteria

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

You may qualify if:

• Signed and dated written informed consent.
• ≥ 18 years of age at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed locally advanced/unresectable or metastatic melanoma.
• Patients who have received prior anti-CTLA-4 or anti-PD-1/PD-L1 for adjuvant treatment of melanoma are eligible if \> 6 months have elapsed between the last dose of adjuvant treatment and starting this study - provided there is no history of life-threatening toxicity related to such prior treatment, or such toxicity is unlikely to re-occur with standard countermeasures (e.g. hormone replacement after endocrinopathy).
• Patients who have received adjuvant therapy with interferon and/or a BRAF inhibitor and/or MEK inhibitor for adjuvant therapy are permitted to enroll.
• At least one measureable target lesion as defined by RECIST 1.1 which can be followed byCT or MRI.
• If located in a previously irradiated area, a tumor lesion is considered a measurable/target lesion only if subsequent disease progression in the lesion has been documented at least 90 days following completion of radiotherapy.
• Adequate organ and bone marrow function ≤ 14 days prior to first dose of protocol-indicated treatment:
• White blood cell count (WBC) ≥ 2,000/mm3
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelets ≥ 75,000/mm3
• Hemoglobin ≥ 8.0 g/dL.
• Serum creatinine ≤ 2.0x upper limit of normal (ULN), or calculated creatinine clearance (CrCl) \> 40 mL/min per the Cockcroft-Gault formula (Appendix 1).
• Total bilirubin ≤ 1.5x ULN (except patients with Gilbert Syndrome, who must have total bilirubin \< 3.0 mg/dL).

You may not qualify if:

• Patients with uveal melanoma.
• Prior systemic anticancer therapy for unresectable or metastatic melanoma.
• Prior treatment with LAG-3 targeted agents.
• Subjects with active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
• Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent.
• Uncontrolled angina within the 3 months prior to consent.
• Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes, or poorly controlled atrial fibrillation).
• QTc prolongation \> 480 msec.
• History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled deep venous thrombosis, etc).
• Cardiovascular disease-related requirement for daily supplemental oxygen.
• History of two or more myocardial infarctions OR two or more coronary revascularization procedures.
• Subjects with history of myocarditis, regardless of etiology.
• A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• Participants with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses \>10 mg daily prednisone or equivalent, are permitted in the absence of active autoimmune disease.

Sponsors & Collaborators

• Elizabeth Davis: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; relatlimab; Ipilimumab

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

Results Point of Contact

• Title: Teresa Melton
• Organization: Vanderbilt University Medical Center

teresa.melton@vumc.org

6159367423

Study Officials

• Elizabeth Davis, MD

  Vanderbilt Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: October 26, 2018
• First Posted: October 30, 2018
• Study Start: January 17, 2019
• Primary Completion: May 28, 2020
• Study Completion: May 28, 2020
• Last Updated: April 20, 2021
• Results First Posted: March 5, 2021

Record last verified: 2021-03

Locations

US (1)