Results of an Open-label, Phase 1a/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced or Metastatic Soft Tissue Sarcoma
Mené sur 41 patients atteints d'un sarcome des tissus mous de stade localement avancé ou métastatique et non résécable, cet essai multicentrique non randomisé de phase Ia/b évalue l'efficacité, du point de vue du taux de contrôle de la maladie, et la toxicité d'un traitement combinant pembrolizumab et olaratumab
Purpose: The study evaluated safety and efficacy of olaratumab+pembrolizumab in patients with unresectable locally advanced/metastatic soft-tissue sarcoma with disease progression on standard treatment. Patients and Methods: This was open-label, multicenter, nonrandomized, phase 1a/1b dose-escalation study followed by cohort expansion (olaratumab+pembrolizumab intravenous infusion). Primary objectives were safety and tolerability. Results: Majority of patients enrolled (41) were female (phase 1a: 9 of 13, phase 1b/dose-expansion cohort [DEC]: 17 of 28), aged <65 years. In phases 1a and 1b, 13 and 26 patients received prior systemic therapy, respectively. Patients received olaratumab 15mg/kg (phase 1a; cohort 1) or 20mg/kg (phase 1a; cohort 2 and phase 1b) and pembrolizumab 200mg (phase 1a/1b). The median (Q1–Q3) duration of therapy (olaratumab) was 6.0 (3.0-11.9) (cohort 1), 14.4 (12.4-20.9) (cohort 2), and 14.0 (6.0-21.8) weeks (DEC). No dose-limiting toxicities and few Grade ≥3 treatment-emergent adverse events (TEAEs, 15 mg/kg: 2 [increased lipase], 20mg/kg: 1 [increased lipase], 1 [colitis], 2 [diarrhea], 3 [anemia]) were reported. Two TEAEs (increased lipase) were related to study discontinuations. Twenty-one patients reported mild (Grade ≤2) TEAE. Phase 1a, disease control rate (DCR):14.3% (1/7, cohort 1); 66.7% (4/6, cohort 2); no responses were reported. Phase 1b, DCR: 53.6% (15/28); objective response rate: 21.4% (6/28) (RECIST and irRECIST criteria). No response in patients with programmed death ligand-1 positive tumors. Conclusions: Antitumor activity was observed in some patients in DEC, combination was well tolerated with manageable safety profile. Further studies are warranted to evaluate efficacy/mechanistic impact of platelet-derived growth factor receptors inhibitor with immune checkpoint modulator coadministration.