(P 015) A SIGNAL FINDING STUDY OF NIVOLUMAB AND RELATLIMAB IN ADVANCED CHORDOMA

Objective: 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 is to assess the safety of nivolumab and relatlimab in subjects with progressive metastatic or locally advanced/unresectable chordoma. Secondary objectives are to ascertain the PFS, RR, and the 4 and 6 month PFS by RECIST 1.1. The main inclusion criteria for the study include age>12, ECOG of 0-1, unresectable, progressive disease with measurable disease by RECIST 1.1, and standard bone marrow, hepatic and renal parameters. Main exclusion criteria include any palliative surgery or XRT 28 days prior to enrollment, immunosuppressive therapy 28 days prior to enrollment, active autoimmune disease within the past 3 years or uncontrolled or significant cardiovascular disease. Blood and pretreatment and on-treatment biopsies for PD-L1 and immune microenvironmental analysis is also being collected.

Results: Out of a planned 20 patients, 10 patients (8 Male,2 Female) consented and 9 were treated on trial: 5 clival/Cspine, 4 sacral,1 thoracic. 9 were conventional and 1 was a chondroid chordoma. 8/10 patients had previous surgery, 6/10 had previous radiation therapy and 5/10 had 1-2 lines of previous systemic therapy, including one who received pembrolizumab. 54 AEs (Grades 1-4) have been noted to date, with 2 events being grade 3-4: nausea. 5 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, 7/9 patients were progression free (77.7%) and at 6 months and 1 year, 4/9 patients were progression free (44.4%). 1/9(9.1%) patients had a PR via RECIST 1.1. Pretreatment biopsies have been obtained in 9/10 patients and blood has been collected on all patients. 1 patient discontinued due to an adverse event (grade 1 myocarditis).

Conclusion: This small 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.