A Signal Finding Phase 2 Study of Nivolumab (Anti-PD-1; BMS-936558; ONO-4538) and Relatlimab (Anti-LAG-3 Monoclonal Antibody; BMS-986016) in Patients With Advanced Chordoma
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- 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
Overview
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.
Detailed Description
PRIMARY OBJECTIVES:
I. To assess the clinical benefit of the combination of nivolumab and relatlimab in patients with advanced chordomas by objective response rate (ORR).
SECONDARY OBJECTIVES:
I. Ascertain the safety of nivolumab in combination with relatlimab in subjects with metastatic or locally advanced/unresectable chordoma by the frequency of adverse events (AEs).
II. Assess the clinical benefit of the combination of nivolumab and relatlimab in patients with advanced chordomas by progression free survival (PFS).
EXPLORATORY OBJECTIVES:
I. Compare response rate (RR) and clinical benefit rate (CBR) in patients whose tumors are PD-L1+ and PD-L1- at baseline.
II. Compare RR and CBR in patients whose tumors are LAG-3+ and LAG-3- at baseline.
III. In the patients who are PD-L1 positive, compare RR and CBR in patients with 1% and 5% tumor membrane staining.
III. Determine the response to treatment based on the baseline mutation load. IV. Determine the ORR and CBR via Choi criteria.
OUTLINE:
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.
After completion of study treatment, participants are followed up within 100 days.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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-
- •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.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
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
Time Frame: Up to 2 years
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.
Secondary Outcomes
- Response rate by Choi criteria(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)
- 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)