Delving into the Latest Updates on Conatumumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Conatumumab (USAN/INN), AMG-655

Target

DR5

Mechanism

DR5 agonists(Tumor necrosis factor receptor superfamily member 10B agonists)

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [5]

Active Indication-

Inactive Indication

Advanced Lung Non-Small Cell CarcinomaAdvanced Malignant Solid NeoplasmCarcinoid Tumor+ [20]

Originator Organization

Amgen, Inc.

Active Organization-

Inactive Organization

Amgen, Inc.

ImmunityBio, Inc.

Takeda Pharmaceutical Co., Ltd.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 9532985H

Source: *****

Sequence Code 9532993L

Source: *****

This is a dose escalation study in female subjects with relapsed ovarian cancer (including epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer). Approximately 30 to 40 subjects will be administered a combination of conatumumab and birinapant.
In the initial dose-escalation stage of the study, adult female subjects will receive conatumumab in combination with increasing doses of birinapant in dose-escalation cohorts to determine the MTD of birinapant when administered with a fixed dose of conatumumab.
In safety expansion stage, adult female subjects will receive conatumumab in combination with birinapant at the MTD of the combination.

Start Date01 Nov 2013

Sponsor / Collaborator

TetraLogic Pharmaceuticals Corp.

NCT01327612

/ CompletedPhase 2

A Phase 2 Open Label Extension Study of Conatumumab and AMG 479

The purpose of this protocol is to allow continued treatment with conatumumab and/or ganitumab, with or without chemotherapy, to participants who completed a separate Amgen-sponsored conatumumab or ganitumab study without disease progression whose previous studies were closed.

Start Date03 Mar 2011

Sponsor / Collaborator

Amgen, Inc.

EUCTR2008-005074-12-ES

/ Not yet recruitingPhase 1

A Phase 1b/2 Open Label, Dose Escalation Study of AMG 655 in Combination with AMG 479 in Subjects with Advanced, Refractory Solid Tumors.--------------------------------------------------------Estudio abierto de fase 1b/2 con escalada de dosis de AMG 655 en combinación con AMG 479 en sujetos con tumores sólidos refractarios y avanzados.

Start Date04 Mar 2009

Sponsor / Collaborator-

100 Clinical Results associated with Conatumumab

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100 Translational Medicine associated with Conatumumab

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100 Patents (Medical) associated with Conatumumab

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36

Literatures (Medical) associated with Conatumumab

04 Oct 2024·Science Advances

The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL

Article

Author: Stanley, Christopher P. ; Le, Natalie ; Pinto, Alexander R. ; Kavurma, Mary M. ; Alwis, Imala ; Powell, Joseph E. ; Robinson, David A. ; Patrick, Ralph ; Aitken, Sarah J. ; Patel, Sanjay ; McGrath, Jordan ; Su, Qian Peter ; Kelland, Elaina ; Harvey, Richard P. ; Dona, Malathi I. ; Loa, Jacky ; Cholan, Pradeep Manuneedhi ; Ganss, Ruth ; Griffith, Thomas S. ; Patil, Manisha S. ; Cartland, Siân P. ; Boccanfuso, Lauren

Reversal of ischemia is mediated by neo-angiogenesis requiring endothelial cell (EC) and pericyte interactions to form stable microvascular networks. We describe an unrecognized role for tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in potentiating neo-angiogenesis and vessel stabilization. We show that the endothelium is a major source of TRAIL in the healthy circulation compromised in peripheral artery disease (PAD). EC deletion of TRAIL in vivo or in vitro inhibited neo-angiogenesis, pericyte recruitment, and vessel stabilization, resulting in reduced lower-limb blood perfusion with ischemia. Activation of the TRAIL receptor (TRAIL-R) restored blood perfusion and stable blood vessel networks in mice. Proof-of-concept studies showed that Conatumumab, an agonistic TRAIL-R2 antibody, promoted vascular sprouts from explanted patient arteries. Single-cell RNA sequencing revealed heparin-binding EGF-like growth factor in mediating EC-pericyte communications dependent on TRAIL. These studies highlight unique TRAIL-dependent mechanisms mediating neo-angiogenesis and vessel stabilization and the potential of repurposing TRAIL-R2 agonists to stimulate stable and functional microvessel networks to treat ischemia in PAD.

31 Dec 2022·Drug deliveryQ2 · MEDICINE

Combined and targeted drugs delivery system for colorectal cancer treatment: Conatumumab decorated, reactive oxygen species sensitive irinotecan prodrug and quercetin co-loaded nanostructured lipid carriers

Q2 · MEDICINE

ArticleOA

Author: Liu, Youqiang ; Zhao, Liyan ; Meng, Qingju ; Liu, Yibing ; Cui, Haijing ; Zhang, Futong ; Zhang, Hongxin

PURPOSE:

Colorectal cancer (CRC) is the third most frequently diagnosed cancer and this study aimed to develop a conatumumab decorated, irinotecan prodrug and quercetin co-loaded delivery system for combined and targeted colorectal cancer treatment.

METHODS:

A conatumumab (C) decorated, irinotecan prodrug (I-p) and quercetin (Q) co-encapsulated NLC (C I-p/Q NLC) was developed. In vitro and in vivo antitumor efficiency of NLC was evaluated on CRC cells and mice xenograft.

RESULTS:

The results showed that the HT-29 cells uptake of C I-p/Q NLC was over 70%. Reactive oxygen species (ROS) sensitive irinotecan prodrug formulation showed improved drug release ability in hypoxic conditions. C I-p/Q NLC showed significantly higher cytotoxicity than non-decorated NLC, single drug-loaded NLC and free drugs. In vivo studies in a CRC-bearing model corroborated the capability of nanoparticles for the inhibition of cancer, leading to a reduction of tumor growth without systemic toxicity.

CONCLUSION:

The conatumumab decorated, ROS sensitive prodrug contained combination nano-system is a promising platform for CRC therapy.

01 Oct 2020·Advances in therapyQ3 · MEDICINE

Efficacy and Safety of Regorafenib in Combination with Chemotherapy as Second-Line Treatment in Patients with Metastatic Colorectal Cancer: A Network Meta-Analysis and Systematic Literature Review

Q3 · MEDICINE

Review

Author: Cai, Yue ; Li, Weiwei ; Xie, Xiaoyu ; Wu, Zehua ; Hu, Huabin ; Zhang, Jianwei ; Deng, Yanhong ; Ling, Jiayu

INTRODUCTION:

Although various therapies are available for the treatment of metastatic colorectal cancer (mCRC), there is lack of head-to-head evidence. Recent studies have demonstrated the efficacy of chemotherapy in combination with different biological agents including regorafenib in second-line therapy in patients with mCRC. We conducted a network meta-analysis (NMA) to estimate the relative efficacy and safety of regorafenib in combination with chemotherapy compared to other biological agents with chemotherapy combinations.

METHODS:

A literature search was conducted in PubMed, Embase, and Cochrane databases to identify all randomized controlled trials (RCTs) evaluating the efficacy and safety of bevacizumab, regorafenib, panitumumab, cetuximab, ramucirumab, conatumumab, ganitumab, and aflibercept in combination with chemotherapy against chemotherapy alone as second-line setting from inception to 7 February 2019 in patients with mCRC. The survival outcomes were analyzed by the frequentist statistical approach (R software, netmeta package) while the level of individual treatment arms was assessed using the Bayesian method (R software, gemtc package).

RESULTS:

We identified 12 articles involving eight RCTs studies analyzing 6805 patients. The studies compared bevacizumab (3), regorafenib (1), panitumumab (2), cetuximab (3), ramucirumab (1), conatumumab (1), ganitumab (1), and aflibercept (1) against chemotherapy alone as comparator. The progression-free survival (PFS) revealed that regorafenib performed better than aflibercept (HR 0.9631, 95% CI 0.6785-1.367), ganitumab (HR 0.7228, 95% CI 0.3985-1.3109), panitumumab (HR 0.9653, 95% CI 0.6781-1.3742), and ramucirumab (HR 0.9206, 95% CI 0.6504-1.303). Regorafenib performed better than bevacizumab (OR 0.797, 95% CI 0.328-1.88) in terms of tumor response. Safety analysis showed that regorafenib performed better in reducing grade ≥ 3 adverse events (AE) than cetuximab and conatumumab, neutropenia than conatumumab, and fatigue than cetuximab.

CONCLUSIONS:

Regorafenib combined with chemotherapy might be a potential alternative to conventional therapeutic options in second-line treatment of patients with metastatic colorectal cancer and could be considered as the best option for treating patients with KRAS and BRAF mutated mCRC. However future RCTs are needed to confirm these results.

100 Deals associated with Conatumumab

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External Link

KEGG	Wiki	ATC	Drug Bank
D09329	Conatumumab	-	DB11646

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 2	US	Amgen, Inc.	03 Mar 2011
Advanced Malignant Solid Neoplasm	Phase 2	PL	Amgen, Inc.	03 Mar 2011
Advanced Malignant Solid Neoplasm	Phase 2	ES	Amgen, Inc.	03 Mar 2011
Carcinoid Tumor	Phase 2	US	Amgen, Inc.	03 Mar 2011
Carcinoid Tumor	Phase 2	PL	Amgen, Inc.	03 Mar 2011
Carcinoid Tumor	Phase 2	ES	Amgen, Inc.	03 Mar 2011
Lymphoma	Phase 2	US	Amgen, Inc.	03 Mar 2011
Lymphoma	Phase 2	PL	Amgen, Inc.	03 Mar 2011
Lymphoma	Phase 2	ES	Amgen, Inc.	03 Mar 2011
Colorectal Cancer	Phase 2	-	ImmunityBio, Inc.	16 Jan 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00630552 (QUILT-2.019, CTgov)	Phase 1/2	Pancreatic adenocarcinoma \| Metastatic Pancreatic Cancer	138	AMG 655 (Phase 1b AMG 655 3mg/kg)	zwakvcslfo(fffrbqxfij) = egdsugfqvm sfggdahqjk (tunpxmqwip, ohmhxjhlis - vfwqwmlgma) View more	-	17 Oct 2024
				AMG 655 (Phase 1b AMG 655 10mg/kg)	zwakvcslfo(fffrbqxfij) = zvotirotid sfggdahqjk (tunpxmqwip, cpttehrypz - ylsndvhbjf) View more
NCT00819169 (CTgov)	Phase 1/2	Sarcoma \| Ovarian Cancer \| Neoplasm Metastasis ... View more	89	AMG 479+AMG 655 (Part 1 Cohort 1)	znxblilyzw(rdfulooziq) = vwmqxksmxb uzgfmixfrz (rclkysgovq, djsvyyljjw - rfccwdalvu) View more	-	20 Aug 2024
				AMG 479+AMG 655 (Part 1 Cohort 2)	znxblilyzw(rdfulooziq) = lfmjgkqqyw uzgfmixfrz (rclkysgovq, npsuzazenq - oeuiryvzxs) View more
NCT01327612 (CTgov)	Phase 2	Sarcoma \| Carcinoid Tumor \| Neoplasm Metastasis ... View more	12	Ganitumab (20050118: Ganitumab 20 mg/kg)	iunfxnnomo(sjxrotpjjt) = ueqicbbvuj qcpbafnpff (rvlhgtplwl, fqgjwbgiqx - lggcedjpjd) View more	-	21 Feb 2021
				Conatumumab (20050171: Conatumumab 0.45 mg/kg)	iunfxnnomo(sjxrotpjjt) = faqyzececg qcpbafnpff (rvlhgtplwl, ugmbamylpk - fziiwfatan) View more
NCT00630786 (CTgov)	Phase 1/2	Rectal Cancer \| Colonic Cancer \| Metastatic Colorectal Carcinoma	53	Conatumumab+Panitumumab	mveixdejfu(hvjlpgsqgz) = fmlveaemxs kiymxdeaqu (umpazlzrjn, nnujqrzota - ywrpdxenes) View more	-	06 Feb 2014
ASCO2010	Phase 1	Solid tumor	9	Conatumumab	nblfyhfpdi(fwhkobgija) = occurred in 2 pts twppsbpuic (nnqepvhruz ) View more	-	20 May 2010
				AMG 479
ASCO2009	Phase 1	Non-Small Cell Lung Cancer	12	AMG 655 + PC	onjeabronz(tijespsjqo) = axogcabfiw jynzahmvxa (hjcdeubqsr, 1.5 - 7.0)	-	20 May 2009