Dual immune checkpoint inhibition with nivolumab and ipilimumab (N+I) in patients with advanced anaplastic thyroid carcinoma (ATC).

Abstract

e18075 Background: There are no standard of care therapies in advanced incurable setting for BRAF wild type (WT) ATC, & after dabrafenib and trametinib (D+T) for BRAF V600E mutant ATC. We previously showed promising clinical activity of dual inhibition with N+I in exploratory cohort of 10 patients (pts) with advanced ATC in a single arm phase II clinical trial, with objective response rate (ORR) of 30% (NCT03246958, Lorch ASCO 2020). Here, we present efficacy and safety outcomes from a real-world cohort of pts with advanced ATC treated with N+I regimen. Methods: We conducted a retrospective cohort study of pts with advanced ATC (unresectable or with distant metastases, DM) who were seen at the Dana-Farber Cancer Institute (DFCI) thyroid cancer center from July 2021 to Jan 2024, received at least one dose of N+I with palliative intent & completed at least one response assessment (data cutoff, 1/31/24). Pts on the DFCI clinical trial were not included. Investigator-assessed ORR (for the first N+I based treatment regimen) and immune-related adverse events (irAEs, collected till cutoff regardless of ongoing treatment) were evaluated. Results: 19 pts with advanced ATC (5: unresectable disease, 14: DM) were included, BRAF WT 12/19 (63%). Median age was 70y (range, 34-81), 68% female. ECOG PS at start was 0-1 in 14/19 (74%), 2 in 4 (21%) & 3 in 1 (5%) pts. 5/19 (26%) pts received N+I concurrently with D+T; 4/5 (80%) in 2nd line after either mixed response or progressive disease (PD) on D+T. Best overall response (BOR) in N+I+D+T group was partial response (PR, 1/5, 20%) & stable disease (SD, 4/5, 80%); ORR 20%. 14/19 (74%) pts received N+I, 12/14 (86%) as 1st line palliative therapy. 5 pts in N+I group (all with DM) received local therapies concurrently (1: debulking thyroid surgery, 3: radiation therapy (RT) to thyroid, & 1: palliative RT to bone DM). BOR in N+I group were: complete response, CR (4/14, 28.6%); PR (3, 21.4%); SD (4, 28.6%); & PD (3, 21.4%); ORR 50%. Excluding 5 pts with concurrent local therapies, ORR was 33.3% (1/9 CR, 2/9 PR).PD-L1 TPS was available for 12/19 pts (4: N+I+D+T, 8: N+I) and ≥1 in all tumors (range, 1-100). In 8 pts in N+I group, ORR stratified by PD-L1 TPS: TPS <50 (range, 1-30): 0% (0/2: 1 SD, 1 PD), & TPS ≥50 (range, 80-100): 83.3% (5/6: 3 CR, 2 PR, 1 PD). Any grade irAEs were observed in 16/19 (84.2%) pts. ≥Grade 3 irAEs occurred in 11/19 (57.9%) pts, most frequent were colitis (5, 26.3%), dermatitis/pruritus (3, 15.8%), myocarditis (2, 10.5%), & adrenal insufficiency (2, 10.5%). There were no treatment-related deaths. Conclusions: In this largest real-world cohort study of pts with advanced ATC, N+I therapy showed high ORR of 50% (congruent with DFCI trial), albeit with high rates of iRAEs. High ORR was seen with PD-L1 TPS ≥50. Survival outcomes and genomic biomarkers, currently under investigation, will be presented at the meeting. N+I merit further investigation in an ATC focused clinical trial.