In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. TPS472-TPS472
Abstract:
TPS472 Background: Immune CPIs have become a standard treatment option for many advanced malignancies, including gastric (G)/GE junction (GEJ) and hepatocellular cancer (HCC), but resistance is inevitable. Data suggests angiogenesis plays a key role in tumor-mediated immune regulation. Vascular endothelial growth factor (VEGF) can inhibit intra-tumor T cell trafficking, while anti-VEGF therapy can improve T cell infiltration, potentially enhancing response to CPIs to overcome resistance. Vorolanib (V), a potent oral VEGFR/PDGFR inhibitor, has anti-angiogenic properties with a favorable toxicity profile. This phase 1b study is aimed to assess the safety and efficacy of V + CPIs, pembrolizumab (P) or nivolumab (N), in pts with advanced solid tumors. Methods: The primary objective is to determine the recommended phase 2 dose (RP2D) of V + CPIs. Secondary objectives include safety, toxicity and objective response rate (ORR) and survival outcomes. Correlatives include analysis of angiogenic factors and tumor infiltrating lymphocytes as response biomarkers in archived tumor tissue and peripheral blood. Key eligibility for dose escalation cohort includes pts with solid tumors who can receive standard P or N, and for dose expansion cohort includes pts with PD-L1+ G/GEJ cancer who progressed on one or two lines of chemo, refused or are not candidates for chemo; or HCC Child-Pugh A treated with or refused sorafenib, ECOG PS 0-1 and adequate organ function. Key exclusions include prior CPI, significant bleeding, thrombosis, autoimmune disease or condition requiring corticosteroid use. A 3+3 design will be utilized to determine maximum tolerated dose and RP2D. V starts at 300 mg PO daily, pts receive N 480 mg IV Q 28-day cycle or P 200 mg IV Q 21-day cycle (max 36 pts). Dose level advancement occurs when all pts complete cycle 1 of assessed level. 20 additional pts (10 HCC, 10 G/GEJ cancer) will be treated at RP2D. Response assessment by RECIST v1.1 occurs Q 3 cycles on P or Q 2 cycles on N. ORR of 20% or greater warrants further investigation. Enrollment is ongoing. Clinical trial information: NCT03511222.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.4_suppl.TPS472
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
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