Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART).
Level 4 - case-series / case-control
Single-arm, non-randomized phase II prospective clinical trial (historically controlled / case-series design)
PubMed 34380663 · doi:10.1136/jitc-2021-002990
What was done
This was a prospective, open-label, multicenter phase II trial (SWOG S1609, DART cohort 51) using a two-stage design to evaluate ipilimumab (1 mg/kg IV every 6 weeks) plus nivolumab (240 mg IV every 2 weeks) in patients with metastatic or unresectable angiosarcoma. The primary endpoint was objective response rate (ORR) by RECIST 1.1; secondary endpoints included progression-free survival (PFS), overall survival, and toxicity.
What was found
Among 16 evaluable patients (median age 68, range 25–81; median 2 prior therapy lines; 9 cutaneous, 7 non-cutaneous), the overall ORR was 25% (4/16). Patients with primary cutaneous tumors of the scalp or face showed an ORR of 60% (3/5). Six-month PFS was 38%. Treatment-related adverse events occurred in 75% of patients (25% grade 3–4), and immune-related adverse events occurred in 68.8% (12.5% grade 3–4: elevated ALT/AST and diarrhea). No grade 5 toxicities were observed. Biomarker testing showed high tumor mutational burden in 1 of 7 assessed patients (who achieved a partial response) and high PD-L1 expression in 2 of 3 assessed patients (one achieved a partial response).
Why it matters
This study provides early prospective clinical trial data demonstrating dual immune checkpoint blockade activity in advanced angiosarcoma, particularly in cutaneous head and neck subtypes.
Limits
The study is constrained by a very small sample size (n=16 evaluable) and a non-randomized, single-arm design without a comparator. Biomarker analyses (TMB and PD-L1) were evaluable only in small subsets of patients, and overall survival numbers were not reported in the abstract.
Cited by
- supports PD-1 inhibitors (such as pembrolizumab) produce an objective response in approximately 18% of patients with metastatic angiosarcoma.