Delving into the Latest Updates on Anti-HB-EGF antibody(U3 Pharma) with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

HBEGF

Action

inhibitors

Mechanism

HBEGF inhibitors(Heparin-binding EGF-like growth factor inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmColorectal CancerOvarian Cancer

Originator Organization

U3 Pharma AG

Active Organization-

Inactive Organization

Daiichi Sankyo, Inc.

Daiichi Sankyo Co., Ltd.

Amgen, Inc.

+ [1]

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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KRAS wild-type colorectal cancers initially responsive to anti-endothelial growth factor receptor (EGFR) antibodies [cetuximab (Cetu)/panitumumab (Pani)] develop acquired resistance. Overexpression of EGFR ligands such as heparin-binding EGF-like growth factor (HB-EGF) may be one resistance mechanism. This phase I study of U3-1565, anti-HB-EGF antibody, and Cetu combination therapy enrolled patients with KRAS wild-type metastatic colorectal cancer who had received two ≤ regimens with fluoropyrimidine, oxaliplatin, irinotecan, and Cetu/Pani and had disease progression on Cetu/Pani. Recommended dose (RD) was determined in the 1st stage, followed by evaluation of efficacy at the RD level in the 2nd-stage. Cetu was given at a loading dose of 400 mg/m² followed by weekly infusions of 250 mg/m² in levels 1 and 0. U3-1565 was administered at a loading dose of 24 mg/m² followed by biweekly infusions of 16 mg/m² in level 1 and 16-12 mg/m² in level 0. Twenty-two patients were enrolled. No dose-limiting toxicities were observed among three patients in level 1 in the first stage, which was determined as RD. Grade 3 or higher adverse events occurred in 59.1%; those in ≥5% of patients were anemia, γ-GTP elevation, and acneiform rash. Overall response rate was 0.0% [95% confidence interval (CI): 0.0%-15.4%] and disease control was achieved in 17 patients (77.3%, 95% CI: 54.6%-92.2%). Median progression-free survival time was 85.0 days (95% CI: 54.0-91.0) and median survival time was 196 days (95% CI: 113.0-306.0). RD was determined as level 1. The efficacy of this combination therapy after progression on Cetu/Pani was negligible. Trial Registration: UMIN000013006.

15 Feb 2019·Investigational New DrugsQ3 · MEDICINE

First-in-human study of the anti-HB-EGF antibody U3-1565 in subjects with advanced solid tumors

Q3 · MEDICINE

Article

Author: Zwick-Wallasch, Esther ; Olszanski, Anthony J ; Jansen, Mendel ; Bendell, Johanna C ; Vandell, Alexander G ; Senaldi, Giorgio ; LoRusso, Patricia M ; Moore, Kathleen N

U3-1565 is a monoclonal antibody directed against heparin-binding epidermal growth factor-like growth factor (HB-EGF), which mediates angiogenesis via induction of vascular endothelial growth factor (VEGF-A). This first-in-human study characterized the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of U3-1565 in subjects with advanced solid tumors. In Part 1 (dose escalation following a modified 3 + 3 design), Cohorts 1-4, U3-1565 was administered at 2, 8, 16, and 24 mg/kg every 3 weeks for Cycle 1 and every 2 weeks thereafter. In Part 1, Cohort 5, and in Part 2 (dose expansion), U3-1565 was administered at 24 mg/kg every week. Thirty-six subjects were enrolled and treated (15 in Part 1; 21 in Part 2). No subject experienced dose limiting toxicity and maximum tolerated dose was not reached. All drug-related events were Grade 1 or 2 in severity, with fatigue and rash predominating. Following treatment with U3-1565, 1 subject with metastatic colorectal cancer experienced partial response and 6 subjects achieved stable disease. Four subjects completed the study main phase (first 12 cycles) and entered the extension phase. Of the 6/36 subjects with high (> 1500 pg/ml) baseline VEGF-A levels, all showed a decrease in VEGF-A (median - 60% [-22% to -97%]). Of the remaining subjects, only 19/30 showed a decrease (median - 18% [-2% to -82%]). Subjects with high VEGF-A baseline levels remained on treatment longer (3/6 entered study extension phase versus 1/30), and were more likely to show disease control (3/6 versus 4/30). In conclusion, U3-1565 demonstrates both proof of mechanism and clinical activity across different tumor types.

100 Deals associated with Anti-HB-EGF antibody(U3 Pharma)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	United States	Daiichi Sankyo, Inc.	01 Jan 2011
Ovarian Cancer	Phase 1	United States	Daiichi Sankyo, Inc.	01 Jan 2011
Colorectal Cancer	Phase 1	Japan	Daiichi Sankyo Co., Ltd.	-
Colorectal Cancer	Phase 1	-	Amgen, Inc.	-
Colorectal Cancer	Phase 1	-	U3 Pharma AG	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AACR2018	Phase 1	Colorectal Cancer	22	U3-1565	(ijtzeybcmk) = ifnrjkifln isuczcvtao (xjbwhwqvoc, 54.0 - 91.0) View more	-	01 Jul 2018
NCT01290471 (ASCO2013) Manual	Phase 1	Advanced Malignant Solid Neoplasm HB-EGF	15	U3-1565	(ygksujtrdm) = fatigue, anemia, and appetite loss, seen in 20, 13, and 7% of cases, respectively fhyusaqutv (izgjazrjqk )	Positive	20 May 2013

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Biosimilar

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