Background
Phase II AcSé Pembrolizumab, open-label multihistotype basket trial (UNICANCER, French AcSé programme). N=97, advanced/metastatic sarcoma across 10 histologic cohorts (LMS, UPS, SFT, angiosarcoma, epithelioid sarcoma, synovial sarcoma, chordoma, ASPS, SMARCA4-deficient thoracic sarcoma, liposarcoma) after ≥1 prior line. NCT02693535.
Interventions and follow up
Treatment: Pembrolizumab 200 mg IV q3w until progression, toxicity, or 24 months
Primary endpoint: ORR per histotype (confirmed PR+CR by RECIST 1.1; ≥2 responses per 20-patient cohort to declare activity)
mFollow up: Median not reported per cohort; interim analysis at data cutoff December 2021
Primary endpoint: ORR per histotype (confirmed PR+CR by RECIST 1.1; ≥2 responses per 20-patient cohort to declare activity)
mFollow up: Median not reported per cohort; interim analysis at data cutoff December 2021
Results
Overall ORR (n=97): 6.2% (6 confirmed responses)
Chordoma (n=20): ORR 15% (3 PRs) — only cohort meeting prespecified threshold
ASPS (n=10): ORR 20% (2 PRs) — below 2/20 threshold (small cohort)
SMARCA4-deficient (n=9): ORR 11% (1 PR)
LMS, UPS, SFT, AS, ES, SS, liposarcoma: 0 confirmed responses
DCR (SD ≥16 wk + PR): higher in chordoma and ASPS; negligible in LMS/SS/AS
Chordoma (n=20): ORR 15% (3 PRs) — only cohort meeting prespecified threshold
ASPS (n=10): ORR 20% (2 PRs) — below 2/20 threshold (small cohort)
SMARCA4-deficient (n=9): ORR 11% (1 PR)
LMS, UPS, SFT, AS, ES, SS, liposarcoma: 0 confirmed responses
DCR (SD ≥16 wk + PR): higher in chordoma and ASPS; negligible in LMS/SS/AS
Adverse events
Grade ≥3 immune-related AEs: ~25%
Most common any-grade: fatigue, rash, hypothyroidism, diarrhea
Pneumonitis grade ≥3: rare
Discontinuation due to AEs: ~10%; no treatment-related deaths
Most common any-grade: fatigue, rash, hypothyroidism, diarrhea
Pneumonitis grade ≥3: rare
Discontinuation due to AEs: ~10%; no treatment-related deaths
Conclusions
Pembrolizumab monotherapy showed meaningful activity only in chordoma (ORR 15%) among 10 histotypes; ASPS activity (20%) limited by small cohort. Most sarcoma histotypes (LMS, UPS, SFT, angiosarcoma, synovial sarcoma, liposarcoma) showed no responses, confirming profound immunotherapy resistance of most soft tissue sarcomas.
Key Limitations
Small per-cohort N (10–20); single-arm, no comparator; ORR surrogate endpoint; interim cutoff with immature survival; heterogeneous histotypes preclude pooled inference.
Clinical Context
No approval for single-agent pembrolizumab in sarcoma. Reinforces that ICI monotherapy is not standard for soft tissue sarcoma per ESMO; activity restricted to select histotypes (chordoma, ASPS, alveolar/clear cell variants). Supports biomarker- and histotype-directed immunotherapy trials.