Delving into the Latest Updates on Dilpacimab with Synapse

Overview

Basic Info

Drug Type

Bispecific antibody

Synonyms

Dilpacimab (USAN/INN), Immunoglobulin, anti-(notch ligand dll4/vascular endothelial growth factor) (synthetic human pr-1283233 heavy chain), disulfide with synthetic human pr-1283233 light chain, dimer

+ [1]

Target

DLL4 x VEGF-A

Mechanism

DLL4 inhibitors(Delta-like protein 4 inhibitors), VEGF-A inhibitors(Vascular endothelial growth factor A inhibitors)

Therapeutic Areas

NeoplasmsDigestive System Disorders

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmMetastatic Colorectal Carcinoma

Originator Organization

AbbVie, Inc.

Active Organization-

Inactive Organization

AbbVie, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Gene Sequence

Sequence Code 9550454H

Source: *****

Sequence Code 9550442L

Source: *****

This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABT-165 when administered as monotherapy and in combination with paclitaxel or 5-fluoruracil, folinic acid and irinotecan (FOLFIRI) or ABBV-181 with/without paclitaxel in subjects with advanced solid tumors. Enrollment to Cohorts A, B were completed and for Cohorts C and D are recruiting.

Start Date08 Aug 2013

Sponsor / Collaborator

AbbVie, Inc.

100 Clinical Results associated with Dilpacimab

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100 Translational Medicine associated with Dilpacimab

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100 Patents (Medical) associated with Dilpacimab

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3

Literatures (Medical) associated with Dilpacimab

01 Sep 2022·Future Oncology

Efficacy and Safety of Dilpacimab (ABT-165) versus Bevacizumab Plus Folfiri in Metastatic Colorectal Cancer: A Phase II Study

Article

Author: Naumovski, Louie ; Strickler, John H ; Blaney, Martha ; Cubillo, Antonio ; Lowe, Thomas ; Wainberg, Zev A ; Kozloff, Mark ; Liang, Jin-Tung ; Matrana, Marc ; Sahtout, Mohammad

Aim: This phase II study investigated safety and efficacy of dilpacimab or bevacizumab plus FOLFIRI in patients with previously treated metastatic colorectal cancer (mCRC). Materials & methods: Overall, 66 patients were treated (n = 34 dilpacimab + FOLFIRI; n = 32 bevacizumab + FOLFIRI). Progression-free survival, overall survival, response rates and tolerability were assessed. Results: Median progression-free survival for dilpacimab + FOLFIRI compared with bevacizumab + FOLFIRI was 3.78 months (95% CI: 2.07–7.20) versus 7.36 months (95% CI: 5.68–10.55) (hazard ratio: 3.57; 95% CI: 1.57–8.11; stratified). Median overall survival: 7.95 months for dilpacimab + FOLFIRI; not reached for bevacizumab + FOLFIRI. Objective response rates: 5.6% for dilpacimab + FOLFIRI and 14.7% for bevacizumab + FOLFIRI. Patients treated with dilpacimab + FOLFIRI experienced serious treatment-related adverse events (n = 4; 11.8%), including one case of intestinal perforation leading to death; none were reported for bevacizumab + FOLFIRI. Conclusion: Treatment with dilpacimab + FOLFIRI was not well tolerated and did not provide clinical benefit to patients with mCRC compared with bevacizumab + FOLFIRI. Clinical Trial Registration: NCT03368859 ( Clinicaltrials.gov )

01 Oct 2021·Molecular Cancer TherapeuticsQ2 · MEDICINE

Phase I Open-Label Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Dilpacimab in Patients with Advanced Solid Tumors

Q2 · MEDICINE

Article

Author: Barve, Minal ; Blaney, Martha ; Nemunaitis, John ; Sledge, George W. ; Motwani, Monica ; Ramanathan, Ramesh K. ; Wang, Lan ; Wainberg, Zev A. ; Yue, Huibin ; Naumovski, Louie ; Strickler, John H. ; Hamilton, Erika P. ; Kasichayanula, Sreeneeranj ; Gordon, Michael S. ; Morgan-Lappe, Susan E.

AbstractDilpacimab (formerly ABT-165), a novel dual-variable domain immunoglobulin, targets both delta-like ligand 4 (DLL4) and VEGF pathways. Here, we present safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy data from a phase I study (trial registration ID: NCT01946074) of dilpacimab in patients with advanced solid tumors. Eligible patients (≥18 years) received dilpacimab intravenously on days 1 and 15 in 28-day cycles at escalating dose levels (range, 1.25–7.5 mg/kg) until progressive disease or unacceptable toxicity. As of August 2018, 55 patients with solid tumors were enrolled in the dilpacimab monotherapy dose-escalation and dose-expansion cohorts. The most common treatment-related adverse events (TRAE) included hypertension (60.0%), headache (30.9%), and fatigue (21.8%). A TRAE of special interest was gastrointestinal perforation, occurring in 2 patients (3.6%; 1 with ovarian and 1 with prostate cancer) and resulting in 1 death. The PK of dilpacimab showed a half-life ranging from 4.9 to 9.5 days, and biomarker analysis demonstrated that the drug bound to both VEGF and DLL4 targets. The recommended phase II dose for dilpacimab monotherapy was established as 3.75 mg/kg, primarily on the basis of tolerability through multiple cycles. A partial response was achieved in 10.9% of patients (including 4 of 16 patients with ovarian cancer). The remaining patients had either stable disease (52.7%), progressive disease (23.6%), or were deemed unevaluable (12.7%). These results demonstrate that dilpacimab monotherapy has an acceptable safety profile, with clinical activity observed in patients with advanced solid tumors.

01 May 2018·Molecular Cancer TherapeuticsQ2 · MEDICINE

ABT-165, a Dual Variable Domain Immunoglobulin (DVD-Ig) Targeting DLL4 and VEGF, Demonstrates Superior Efficacy and Favorable Safety Profiles in Preclinical Models

Q2 · MEDICINE

Article

Author: Ambrosi, Dominic J. ; Eaton, Lucia J. ; Morgan-Lappe, Susan E. ; Foster-Duke, Kelly D. ; DiGiammarino, Enrico L. ; Gao, Wenqing ; Gu, Jijie ; Jiang, Fang ; Akella, Surekha S. ; Haasch, Deanna L. ; Panchal, Sanjay C. ; Zhang, Catherine ; Hickson, Jonathan A. ; Naumovski, Louie ; Ralston, Sherry L. ; Mudd, Sarah R. ; Li, Yingchun

AbstractAntiangiogenic therapy is a clinically validated modality in cancer treatment. To date, all approved antiangiogenic drugs primarily inhibit the VEGF pathway. Delta-like ligand 4 (DLL4) has been identified as a potential drug target in VEGF-independent angiogenesis and tumor-initiating cell (TIC) survival. A dual-specific biologic targeting both VEGF and DLL4 could be an attractive strategy to improve the effectiveness of anti-VEGF therapy. ABT-165 was uniquely engineered using a proprietary dual-variable domain immunoglobulin (DVD-Ig) technology based on its ability to bind and inhibit both DLL4 and VEGF. In vivo, ABT-165 induced significant tumor growth inhibition compared with either parental antibody treatment alone, due, in part, to the disruption of functional tumor vasculature. In combination with chemotherapy agents, ABT-165 also induced greater antitumor response and outperformed anti-VEGF treatment. ABT-165 displayed nonlinear pharmacokinetic profiles in cynomolgus monkeys, with an apparent terminal half-life > 5 days at a target saturation dose. In a GLP monkey toxicity study, ABT-165 was well-tolerated at doses up to 200 mg/kg with non-adverse treatment–related histopathology findings limited to the liver and thymus. In summary, ABT-165 represents a novel antiangiogenic strategy that potently inhibits both DLL4 and VEGF, demonstrating favorable in vivo efficacy, pharmacokinetic, and safety profiles in preclinical models. Given these preclinical attributes, ABT-165 has progressed to a phase I study. Mol Cancer Ther; 17(5); 1039–50. ©2018 AACR.

100 Deals associated with Dilpacimab

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External Link

KEGG	Wiki	ATC	Drug Bank
D11642	-	-	DB16140

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Colorectal Carcinoma	Phase 2	TW	AbbVie, Inc.	20 Mar 2018
Metastatic Colorectal Carcinoma	Phase 2	US	AbbVie, Inc.	20 Mar 2018
Metastatic Colorectal Carcinoma	Phase 2	ES	AbbVie, Inc.	20 Mar 2018
Metastatic Colorectal Carcinoma	Phase 2	KR	AbbVie, Inc.	20 Mar 2018
Metastatic Colorectal Carcinoma	Phase 2	CA	AbbVie, Inc.	20 Mar 2018
Metastatic Colorectal Carcinoma	Phase 2	BE	AbbVie, Inc.	20 Mar 2018
Advanced Malignant Solid Neoplasm	Phase 2	US	AbbVie, Inc.	08 Aug 2013

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03368859 (Pubmed)	Phase 2	Metastatic Colorectal Carcinoma	66	Dilpacimab + FOLFIRI	(phvwbndeno) = Patients treated with dilpacimab + FOLFIRI experienced serious treatment-related adverse events (n = 4; 11.8%), including one case of intestinal perforation leading to death; none were reported for bevacizumab + FOLFIRI. zhwnlgsszn (qagmxpvlrd ) View more	Negative	03 Aug 2022
NCT03368859 (Pubmed)	Phase 2	Metastatic Colorectal Carcinoma	66	Bevacizumab + FOLFIRI		Negative	03 Aug 2022
NCT01946074 (Pubmed \| Mol Cancer Ther) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	55	Dilpacimab	(etwmxdqnak) = nqyrpecnjs cixcmmhwoe (kbyfsdyhrv ) View more	Positive	01 Oct 2021
NCT03368859 (Phase 1b open-label study, CTgov)	Phase 2	Metastatic Colorectal Carcinoma	70	ABT-165+Leucovorin+irinotecan+Fluorouracil - bolus (ABT-165 Plus FOLFIRI)	liiaowsprs(wpphnvxwrj) = dvcrosbhyc jyyenvoglc (vpdmteqvbe, ilytpqcttp - ofpdnfnqpa) View more	-	09 Feb 2021
NCT03368859 (Phase 1b open-label study, CTgov)	Phase 2	Metastatic Colorectal Carcinoma	70	Leucovorin+Bevacizumab+irinotecan+Fluorouracil - bolus (Bevacizumab Plus FOLFIRI)	liiaowsprs(wpphnvxwrj) = wmetzpqbtt jyyenvoglc (vpdmteqvbe, afwtnoizpc - wqthcqwehj) View more	-	09 Feb 2021
NCT03368859 (Phase 1b open-label study, ESMO_GI2018)	Phase 1	Colorectal Cancer Second line KRAS mutation status	16	ABT-165 2.5 mg/kg plus FOLFIRI	(ilbrionofn) = wjpcjhctsc ejovtmywsr (dnfkruhpqy ) View more	Positive	20 Jun 2018
NCT01946074 (ASCO2016)	Phase 1	HR-positive/HER2-low Solid Tumors	54	ABT-165	xlikwegene(pylsdobwdn) = Other AEs of interest with respect to mechanism of action included ... gastrointestinal perforation (GIP) (3.7%) zzjdyklqnl (xacryyixge ) View more	Positive	20 May 2016