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A Phase 1/2 Trial Combining Avelumab and Trabectedin for Advanced Liposarcoma and Leiomyosarcoma.
Wagner, Michael J; Zhang, Yuzheng; Cranmer, Lee D; Loggers, Elizabeth T; Black, Graeme; McDonnell, Sabrina; Maxwell, Shannon; Johnson, Rylee; Moore, Roxanne; Hermida de Viveiros, Pedro; Aicher, Lauri; Smythe, Kimberly S; He, Qianchuan; Jones, Robin L; Pollack, Seth M.
Afiliación
  • Wagner MJ; Medical Oncology, University of Washington, Seattle, Washington.
  • Zhang Y; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Cranmer LD; Seattle Cancer Care Alliance, Seattle, Washington.
  • Loggers ET; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Black G; Medical Oncology, University of Washington, Seattle, Washington.
  • McDonnell S; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Maxwell S; Seattle Cancer Care Alliance, Seattle, Washington.
  • Johnson R; Medical Oncology, University of Washington, Seattle, Washington.
  • Moore R; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Hermida de Viveiros P; Seattle Cancer Care Alliance, Seattle, Washington.
  • Aicher L; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Smythe KS; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • He Q; Medical Oncology, University of Washington, Seattle, Washington.
  • Jones RL; Medical Oncology, University of Washington, Seattle, Washington.
  • Pollack SM; Medical Oncology, University of Washington, Seattle, Washington.
Clin Cancer Res ; 28(11): 2306-2312, 2022 06 01.
Article en En | MEDLINE | ID: mdl-35349638
PURPOSE: Leiomyosarcoma and liposarcoma frequently express PD-L1 but are generally resistant to PD-1/PD-L1 inhibition (immune checkpoint inhibitor). Trabectedin is FDA approved for leiomyosarcoma and liposarcoma. This study aimed to evaluate the safety and efficacy of trabectedin with anti-PD-L1 antibody avelumab in patients with advanced leiomyosarcoma and liposarcoma. PATIENTS AND METHODS: A single-arm, open-label, Phase 1/2 study tested avelumab with trabectedin for advanced leiomyosarcoma and liposarcoma. The phase I portion evaluated safety and feasibility of trabectedin (1, 1.2, and 1.5 mg/m2) with avelumab at standard dosing. Primary endpoint of the phase II portion was objective response rate (ORR) by RECIST 1.1. Correlative studies included T-cell receptor sequencing (TCRseq), multiplex IHC, and tumor gene expression. RESULTS: 33 patients were evaluable: 24 with leiomyosarcoma (6 uterine and 18 non-uterine) and 11 with liposarcoma. In Phase 1, dose-limiting toxicities (DLT) were observed in 2 of 6 patients at both trabectedin 1.2 and 1.5 mg/m2. The recommended Phase 2 dose (RP2D) was 1.0 mg/m2 trabectedin and 800-mg avelumab. Of 23 patients evaluable at RP2D, 3 (13%) had partial response (PR) and 10 (43%) had stable disease (SD) as best response. Six-month PFS was 52%; median PFS was 8.3 months. Patients with PR had higher Simpson Clonality score on TCRseq from peripheral blood mononuclear cells versus those with SD (0.182 vs. 0.067, P = 0.02) or progressive disease (0.182 vs. 0.064, P = 0.01). CONCLUSIONS: Although the trial did not meet the primary objective response rate endpoint, PFS compared favorably with prior studies of trabectedin warranting further investigation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leiomiosarcoma / Liposarcoma Límite: Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leiomiosarcoma / Liposarcoma Límite: Humans Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos