Phase 2 trial of pembrolizumab (PEM) plus granulocyte macrophage colony stimulating factor (GM-CSF) in advanced biliary cancers (ABC): Clinical outcomes and biomarker analyses.

医学 彭布罗利珠单抗 内科学 肿瘤科 不利影响 胃肠病学 无容量 癌症 免疫疗法
作者
Robin Kate Kelley,Emily Mitchell,Spencer C. Behr,Jimmy J. Hwang,Bridget P. Keenan,Sarah E. Umetsu,John D. Gordan,Andrew H. Ko,Pelin Cinar,Chloé E. Atreya,Katherine Van Loon,Thomas Weber,Zoe Ngo,Zoe Quandt,Chien‐Ying Liu,Alan P. Venook,Lawrence Fong
出处
期刊:Journal of Clinical Oncology [Lippincott Williams & Wilkins]
卷期号:36 (15_suppl): 4087-4087 被引量:9
标识
DOI:10.1200/jco.2018.36.15_suppl.4087
摘要

4087 Background: The efficacy of immune checkpoint inhibition (CPI) has not been established in ABC. The combination of CPI plus the myeloid cytokine GM-CSF was safe with prolonged overall survival (OS) compared to CPI monotherapy in melanoma. This phase 2 trial evaluates the safety, efficacy, and biomarkers of PEM in combination with 2 cycles of low dose induction GM-CSF in ABC (NCT02703714). Methods: Design: Simon’s 2-stage. Key eligibility: ABC after ≥ 1 standard therapy, no prior CPI, bilirubin ≤ 1.5xULN. Treatment: PEM 200 mg IV Q3 weeks plus GM-CSF 250 µg SC days 1-14 Q3 weeks for 2 cycles. Endpoints: 1◦: Overall response rate (ORR) by RECIST 1.1 with H0 5% vs. H1 20%. Key 2◦: Safety, progression-free survival at 6 months (PFS6), OS, tumor PD-L1 expression. Exploratory: CA 19-9 levels, tumor microsatellite (in)stability (MSI, MSS), tumor mutation burden (TMB), tumor and peripheral immune cell profiling. Results: Accrual has completed with 27 patients enrolled 5/2016-9/2017: Stage 1/2 9/18; F/M 13/14; median age 61; intra-/extra-hepatic 74%/26%; stage IVA/B 85%, II/III 15%; median prior therapies 2 (range 1-6); MSI/MSS/unknown 1/19/7; TMB high+int./low/unknown 5/11/11. Adverse events (AE): Related ≥ grade (Gr)3 AE in 2 (7%) (1 each immune-related (ir)AE of Gr4 diabetes mellitus and Gr3 fever); irAE requiring steroids in 3 (11%); endocrine irAE in 8 (30%). Disposition: 20 pts discontinued for PD, 1 for Gr2 irAE neuropathy/arthralgia, 1 for unrelated AE; 5 remain on treatment. Median cycles: 6 cycles (range 2-28+). ORR: Confirmed partial response (cPR) in 5 (19%) (95% CI: 3-34%) (1 MSI, 4 MSS); cPR or stable disease (SD) ≥ 6 months in 9 (33%). PFS6: 35% (95% CI: 15-54%); median OS: not reached. Endocrine irAE, CA 19-9 changes ≥ 50%, hepatitis C virus (HCV), and TMB were associated with efficacy in univariate analyses. PD-L1+ in ≥ 1% cells was present in 3/10 (30%) pre-treatment samples but was not associated with ORR or PFS6; additional PD-L1 results are pending. Conclusions: PEM plus induction GM-CSF is safe and well-tolerated in ABC. Prolonged responses and PFS in MSS ABC along with candidate biomarkers warrant further study in larger sample. Clinical trial information: NCT02703714).

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