Nivolumab and Relatlimab in Treating Participants With Advanced Chordoma

NCT03623854 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 18-000597NCI-2018-01517
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well nivolumab and relatlimab work in treating participants with chordoma that has spread to other places in the body. Monoclonal antibodies, such as nivolumab and relatlimab, may interfere with the ability of tumor cells to grow and spread.

Conditions

Chordoma; Locally Advanced Chordoma; Metastatic Chordoma; Unresectable Chordoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) defined as the number of subjects with a best objective response (BOR) of confirmed complete response (CR) or partial response (PR) divided by the number of subjects

  BOR is defined as the best response designation, as determined by the principal investigator, recorded between the date of randomization and the date of objectively documented progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or the date of subsequent therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first.

  Up to 2 years

Secondary Outcomes (4)

• Response rate by Choi criteria

  Up to 2 years

• Progress free survival (PFS) time

  At 4 months and 6 months

• Clinical benefit rate as defined by adding CR, PR, and stable disease (SD)

  Up to 2 years

• Incidence of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 2 years

Study Arms (1)

Treatment (nivolumab and relatlimab)

EXPERIMENTAL

Participants receive nivolumab intravenously (IV) over 60 minutes and relatlimab via infusion over 60 minutes on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab; Biological: Relatlimab

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (nivolumab and relatlimab)

Relatlimab BIOLOGICAL

Given via infusion

Also known as: BMS-986016, BMS986016, Immunoglobulin G4, Anti-(human Lymphocyte Activation Gene-3 Protein) (Human Heavy Chain), Disulfide with Human Light Chain, Dimer

Treatment (nivolumab and relatlimab)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Capable of providing informed consent and complying with trial procedures.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
• Life expectancy \> 12 weeks.
• Histological confirmation of chordoma.
• Adequate archival tissue must be available within 6 months prior to signing consent. If not, an adequate tumor specimen obtained by either excisional biopsy, incisional biopsy or core needle biopsy must be sent to the central pathology lab for evaluation. The material must measure at least 0.8 x 0.1 cm in size or contain at least 50 tumor cells.
• Locally advanced, unresectable, and/or metastatic chordoma with evidence of disease progression by either computed tomography (CT) or magnetic resonance imaging (MRI) scan, or loss of neurologic function on or after the last cancer therapy within 6 months prior to randomization.
• Measurable tumor lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• Women must not be able to become pregnant (e.g., post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. (Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.)
• Women must not be breastfeeding.
• Males and their female partner(s) of child-bearing potential must use 2 forms of effective contraception (condom or vasectomy for males) from the last menstrual period of the female partner during the study treatment and agree to continue use for 6 months after the final dose of study treatment.
• Reproductive status:
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) at screening.
• Women must not be breastfeeding.
• Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatments plus 24 weeks after the last dose of study treatment.

You may not qualify if:

• Palliative surgery and/or radiation treatment within 28 days prior to date of randomization; also no steroids are permitted as of 28 days of starting the study.
• Inability to give informed consent.
• Exposure to any therapeutic agent (investigational or conventional) within 7 days of date of randomization or to any agent for which 5 half lives have not elapsed.
• An inadequate tumor specimen as defined by the central pathologist.
• History of other malignancies except cured basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix; for other malignancies, must be documented to be free of cancer for \>= 2 years. All other cases can be considered on a case by case basis at the discretion of the principal investigator.
• Current, serious, clinically significant cardiac arrhythmias or hypertension that is not adequately controlled, per investigator discretion.
• Concomitant use of medications associated with a high incidence of QT prolongation will require clearance by medical monitor.
• Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. The Medical Monitor should be contacted for any uncertainties.
• Any condition that might interfere with the subject?s participation in the study, safety, or in the evaluation of the study results.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
• Prior exposure to any anti-LAG3 antibodies. (prior PD-1/PD-L1 antibodies are permitted).
• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of nivolumab, with the exceptions of intranasal, topical, and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent (use for brain metastases is not permitted 28 days prior to start of therapy).
• Active or prior documented autoimmune disease within the past 3 years.
• Note: Subjects with active, known or suspected autoimmune disease such as vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Chordoma

Interventions

Nivolumab; relatlimab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Arun Singh

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2018
• First Posted: August 9, 2018
• Study Start: April 3, 2019
• Primary Completion: September 28, 2023
• Study Completion: September 28, 2023
• Last Updated: April 16, 2024

Record last verified: 2023-09

Locations

US (1)