Results of an Open-label, Phase Ia/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced, or Metastatic Soft-Tissue Sarcoma.
Clin Cancer Res
; 29(17): 3320-3328, 2023 09 01.
Article
en En
| MEDLINE
| ID: mdl-37382656
ABSTRACT
PURPOSE:
The study evaluated safety and efficacy of olaratumab + pembrolizumab in patients with unresectable locally advanced/metastatic soft-tissue sarcoma (STS) with disease progression on standard treatment. PATIENTS ANDMETHODS:
This was open-label, multicenter, nonrandomized, phase Ia/Ib dose-escalation study followed by cohort expansion (olaratumab + pembrolizumab intravenous infusion). Primary objectives were safety and tolerability.RESULTS:
The majority of patients enrolled (n = 41) were female [phase Ia 9 of 13, phase Ib/dose-expansion cohort (DEC), 17 of 28], aged < 65 years. In phases Ia and Ib, 13 and 26 patients received prior systemic therapy, respectively. Patients received olaratumab 15 mg/kg (phase Ia; cohort 1) or 20 mg/kg (phase Ia; cohort 2 and phase Ib) and pembrolizumab 200 mg (phase Ia/Ib). 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 [TEAE; 15 mg/kg 2 (increased lipase); 20 mg/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) TEAEs [phase Ia, disease control rate (DCR)14.3% (1/7, cohort 1); 66.7% (4/6, cohort 2); no responses were reported; phase Ib, DCR 53.6% (15/28); objective response rate 21.4% (6/28; RECIST and irRECIST criteria)]. No response was observed in patients with programmed death ligand-1-positive tumors.CONCLUSIONS:
Antitumor activity was observed in some patients in DEC, and combination was well tolerated with manageable safety profile. Further studies are warranted to evaluate the efficacy and mechanistic impact of platelet-derived growth factor receptor inhibitors with immune checkpoint modulator coadministration.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sarcoma
/
Neoplasias de los Tejidos Blandos
/
Neoplasias Primarias Secundarias
Tipo de estudio:
Clinical_trials
Límite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2023
Tipo del documento:
Article
País de afiliación:
Bélgica