A signal-finding study of nivolumab and relatlimab in patients with advanced chordoma.

person Aaron Burkenroad Division of Hematology and Oncology, UCLA Department of Medicine, Santa Monica, CA info_outline Aaron Burkenroad, Arun S. Singh, Bartosz Chmielowski, Sandra Brackert, Noah Federman, Anahis Hagopian, John A Glaspy, Joseph Kendal, Lauren E Wessel, Francis J. Hornicek, Nicholas M. Bernthal

Authors person Aaron Burkenroad Division of Hematology and Oncology, UCLA Department of Medicine, Santa Monica, CA info_outline Aaron Burkenroad, Arun S. Singh, Bartosz Chmielowski, Sandra Brackert, Noah Federman, Anahis Hagopian, John A Glaspy, Joseph Kendal, Lauren E Wessel, Francis J. Hornicek, Nicholas M. Bernthal Organizations Division of Hematology and Oncology, UCLA Department of Medicine, Santa Monica, CA, Division of Hematology and Medical Oncology, Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, Departments of Pediatrics and Orthopaedic Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, Division of Hematology and Oncology, UCLA Department of Medicine, Los Angeles, CA, Cumming School of Medicine, Department of Surgery, Orthopedic Surgery, Calgary, AB, Canada, Department of Orthopedic Surgery, UCLA, Santa Monica, CA, Department of Orthopedic Surgery, University of Miami, Miami, CA Abstract Disclosures Research Funding Bristol Myers Squibb Background: Chordomas are derived from notochordal remnants and are typically treated with surgery and radiation therapy. For advanced chordomas, there are no approved systemic therapies. Preclinical evidence and anecdotal reports have indicated that the immune system is active in chordomas and that there may be a role for immunomodulation in treating this disease. Methods: This study is a single-arm, signal-finding trial in patients with advanced chordoma treated with the anti PD-1 antibody nivolumab (480 mg Q4 weeks up to 2 years) and the anti-LAG3 antibody relatlimab (160 mg Q4 weeks up to 2 years). The primary objective of this study was to assess the safety of nivolumab and relatlimab in subjects with progressive metastatic or locally advanced/unresectable chordoma. Secondary objectives were to ascertain the median progression free survival (PFS), response rate (RR), and the 4- and 6-month PFS by RECIST 1.1. Results: Out of a planned enrollment of 20 patients, 10 patients (8 Male, 2 Female) were consented and treated on trial. Enrolled patients had the following sites of involvement: 5 clival/c-spine, 4 sacral, and 1 thoracic. Nine had conventional subtype chordoma and 1 had chondroid subtype. Eight of the 10 patients had previous surgery, 6 had previous radiation therapy and 5 had 1-2 lines of prior systemic therapy, including one who received pembrolizumab. Pretreatment biopsies were obtained from 9 out of 10 patients and blood has been collected on all patients. Nine patients were evaluable for study outcomes. A total of 64 AEs (Grades 1-4) have been noted to date, with 6 events being classified as grade 3-4: nausea, facial pain, headache, and pulmonary embolism. Five serious adverse events (SAEs) were noted in patients on treatment: headache (2), asthma (1), myocarditis (1), and sepsis (1). The median PFS of the 9 evaluable patients was 21.4 weeks. At 4 months, 7 out of 9 patients were progression free (77.7%). At 6 months, 4 out of 9 patients remained progression free (44.4%) and had continued progression-free survival at 1 year. One out of 9 (9.1%) patients had a PR via RECIST 1.1. One patient discontinued treatment due to an adverse event (grade 1 myocarditis). Conclusions: This signal-finding study indicated that some patients with advanced chordomas can receive benefit with relatlimab in combination with nivolumab. The combination was well-tolerated and no new safety signals were found in this rare patient population. Correlative studies are ongoing. The study was closed for slow accrual. Clinical trial information: NCT03623854.