Nivolumab, BMS-936558 in Combination with Relatlimab, BMS-986016 in Patients with Metastatic Melanoma Naïve to Prior Immunotherapy in the Metastatic Setting

NCT03743766 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 18-071
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of this study is to evaluate the antitumor activity of relatlimab and nivolumab in combination in subjects with unresectable or metastatic melanoma who have not received prior treatment with immunotherapy.

Conditions

Melanoma

Keywords

Stage IIIB; Stage IIIC; Stage IIID; Stage IV; immune checkpoint blockade (ICB); Lymphocyte activation gene-3 (LAG3; CD223); immunotherapy

Outcome Measures

Primary Outcomes (4)

• Change in LAG3 Expression

  LAG3 (cell surface molecule expressed on activated T cells) expression is either positive (present) or not detectable if absent after completion of lead-in phase.

  At baseline and at 4 weeks

• Change in PD1 expression

  PD1 (programmed cell death protein 1) expression is either positive (present) or not detectable if absent after completion of lead-in phase

  At baseline and at 4 weeks

• Change in Tumor Size

  Tumor size will be assessed per Response Evaluation Criteria in Solid Tumors. Per RECIST 1.1, Tumour lesions: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of: * 10 mm by CT scan (CT scan slice thickness no greater than 5 mm; see Appendix II on imaging guidance). * 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable). * 20 mm by chest X-ray.

  At baseline and at 4 weeks

• Overall Response Rate (ORR)

  Number of participants experiencing Complete Response (CR) + Number of participants experiencing Partial Response (PR)/total patients assessed. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  Beginning at 12 weeks post initial treatment, up to 4 years

Secondary Outcomes (17)

• Clinical Benefit Rate

  12 weeks post initial treatment, up to 4 years

• Duration of Response

  12 weeks post initial treatment, up to 4 years

• Progression-free Survival (PFS)

  Up to 4 years

• Overall Survival (OS)

  Up to 4 years

• LAG3 Expression

  At week 16 (2 weeks post combination treatment (3 cycles))

Other Outcomes (4)

• Single cell RNA sequencing

  2 weeks

• Single cell RNA sequencing

  At 4 weeks post Cycle 1

• Single cell RNA sequencing

  At week 16 (12 weeks post combination treatment (3 cycles)

Study Arms (3)

Relatlimab

EXPERIMENTAL

Cycle 1: Relatlimab (BMS-986016) is supplied as a sterile 10mg/mL formulation to be administered as an intravenous (IV) infusion at 160 mg IV for the first 4 weeks (cycle 1). Cycle 2+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV once every 4 weeks.

Drug: Relatlimab

Nivolumab

EXPERIMENTAL

Cycle 1: Nivolumab (BMS-936558) is supplied as a sterile 10-mg/mL formulation to be administered as an IV infusion at 480 mg IV for the first 4 weeks. Cycle 2+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV once every 4 weeks.

Drug: Nivolumab

Relatlimab + Nivolumab

EXPERIMENTAL

Cycle 1+: Combination therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV for the first 4 weeks (Cycle 1), then once every 4 weeks afterwards.

Drug: Relatlimab + Nivolumab

Interventions

Relatlimab DRUG

Relatlimab (BMS-986016) - 10mg/mL formulation to be administered as an intravenous (IV) infusion at 160 mg IV.

Also known as: BMS-986016

Relatlimab

Nivolumab DRUG

Nivolumab (BMS-936558) - 10-mg/mL formulation to be administered as an IV infusion at 480 mg IV.

Also known as: BMS-936558

Nivolumab

Relatlimab + Nivolumab DRUG

Combination (Relatlimab + Nivolumab) therapy will be administered by sequential infusion. Nivolumab administered at 480 mg IV followed by infusion of relatlimab at 160 mg IV.

Also known as: BMS-986016 and BMS-936558

Relatlimab + Nivolumab

Eligibility Criteria

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

You may qualify if:

• Men or women 18 years of age or older meeting AJCC 8th edition criteria for unresectable stage IIIB, stage IIIC, stage IIID, or stage IV melanoma who have not received treatment with immunotherapy in the metastatic setting

You may not qualify if:

• Known or suspected CNS metastases, with the following exceptions:
• Subjects with controlled brain metastases will be allowed to enroll. Controlled brain metastases are defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment at the time of consent. Subjects must be off steroids for at least 2 weeks prior to randomization.
• Subjects with signs or symptoms of brain metastases are not eligible unless brain metastases are ruled out by computed tomography or magnetic resonance imaging.
• Active autoimmune disease requiring treatment, with the exception of type 1 diabetes mellitus, vitiligo, resolved childhood asthma/atopy, controlled hyper/hypothyroidism, hypoadrenalism or hypopituitarism.
• Prior systemic treatment in the metastatic setting, including anti-PD1, anti-PDL1, anti-PDL2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways; or chemotherapy.
• Prior adjuvant treatment with anti-PD1, anti-PDL1, and/or anti-LAG3 antibody. Note that prior adjuvant treatment with targeted therapy (e.g. BRAF/MEK inhibition), anti-CTLA4, or treatment not otherwise specified above would be permitted.
• Ocular melanoma

Sponsors & Collaborators

• John Kirkwood: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

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

Study Officials

• John Kirkwood, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: In the 4-week lead-in phase, subjects will be randomized to one of three arms for 1 cycle (4 weeks) of lead-in treatment with nivolumab, relatlimab, or the combination of nivolumab and relatlimab. Following 1 cycle of lead-in treatment, all subjects will be treated with the combination of relatlimab and nivolumab every 4 weeks.

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: November 16, 2018
• Study Start: March 29, 2019
• Primary Completion: July 3, 2024
• Study Completion: July 3, 2024
• Last Updated: September 25, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)