In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 369-369
Abstract:
369 Background: The first-in-class recombinant fusion protein IPA blocks WNT signaling by binding WNT ligands, and in combination with Nab-P/G caused tumor regression in pt-derived PC xenografts. This open-label Phase 1b dose escalation study evaluated the combination of IPA with Nab-P/G in untreated mPC pts using a standard 3+3 design. Methods: Dose escalation in cohort 1 started with Nab-P 125 mg/m 2 and G 1000 mg/m 2 given on days 1, 8 ,15, with IV IPA (3.5 mg/kg) on days 1 and 15, in 28-day cycles. Due to fragility fractures seen in other studies with similar targeted agents, cohorts 2-4 were 6-pt cohorts treated with weekly Nab-P/G + IPA 3 mg/kg (cohort 2) or 5 mg/kg (cohorts 3 and 4) on day 1. These cohorts included strict bone marker monitoring and use of bisphosphonates as indicated. Based on pre-clinical data suggesting improved efficacy with sequential dosing, pts in Cohort 4 received IPA on day 1 followed by weekly chemotherapy starting on day 3 of 28-day cycles. Objectives included safety, maximum tolerated dose, recommended phase 2 dose, pharmacokinetics, immunogenicity, pharmacodynamics, and preliminary efficacy. Results: Twenty-six pts in four dose escalation cohorts were enrolled, five in the cohort one and seven each in cohorts 2-4. Median age was 61.7 years and a majority were male (73%). Reported IPA-related AEs of any grade occurring in ≥ 20% of pts included fatigue, nausea, vomiting, anorexia and pyrexia. IPA-related AEs grade ≥ 3 included 2 events of AST elevation, and 1 each of nausea, maculopapular rash, vomiting and WBC decrease. No dose limiting toxicities or fragility fractures were observed. Of 26 evaluable pts, 9 (34.6%) had a partial response and 12 (46.2%) stable disease, with clinical benefit rate of 80.8%. The study was closed due to termination of the program by the sponsor. At time of data cut off, median progression free survival was 5.9 months (95% CI 3.4-18.4), median overall survival was 9.7 months (95% CI: 7.0-14). One pt remains on therapy under compassionate use with ongoing response. Conclusions: IPA can be safely administered with Nab-P and G in pts with mPC. Additional studies targeting the WNT pathway in pancreatic cancer are warranted. Clinical trial information: NCT02050178.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.4_suppl.369
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
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