Delving into the Latest Updates on Conatumumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Conatumumab (USAN/INN)

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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Gene Sequence

Sequence Code 9532993L

Source: *****

Sequence Code 9532985H

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.

EUCTR2010-022270-14-ES / Not yet recruitingPhase 2

Estudio abierto de extensión de fase 2 con conatumumab .A Phase 2 Open Label Extension Study of Conatumumab.

Start Date11 Feb 2011

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

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

PURPOSEColorectal 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.METHODSA 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.RESULTSThe 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.CONCLUSIONThe 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: Zhang, Jianwei ; Ling, Jiayu ; Hu, Huabin ; Xie, Xiaoyu ; Cai, Yue ; Wu, Zehua ; Li, Weiwei ; Deng, Yanhong

INTRODUCTIONAlthough 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.METHODSA 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).RESULTSWe 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.CONCLUSIONSRegorafenib 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
Colonic Cancer	Phase 2	US	Amgen, Inc.	01 Oct 2007
Pancreatic adenocarcinoma	Phase 2	US	ImmunityBio, Inc.	01 Jun 2007
Secondary malignant neoplasm of pancreas	Phase 2	US	ImmunityBio, Inc.	01 Jun 2007
Non-Small Cell Lung Cancer	Phase 2	EU	Amgen, Inc.	-
Non-Small Cell Lung Cancer	Phase 2	CA	Amgen, Inc.	-
Non-Small Cell Lung Cancer	Phase 2	CA	Amgen, Inc.	-
Non-Small Cell Lung Cancer	Phase 2	AU	Amgen, Inc.	-
Non-Small Cell Lung Cancer	Phase 2	AU	Amgen, Inc.	-
Non-Small Cell Lung Cancer	Phase 2	EU	Amgen, Inc.	-
Pancreatic Cancer	Phase 2	US	Amgen, Inc.	-

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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 \| Secondary malignant neoplasm of pancreas	138	AMG 655 (Phase 1b AMG 655 3mg/kg)	wosqvzgquy(qyqhnjuvrk) = wuqnfjlnfu zijzxbkxzw (jrbdvbxkvz, jsxkmesvem - jopuodiwpw) View more	-	17 Oct 2024
				AMG 655 (Phase 1b AMG 655 10mg/kg)	wosqvzgquy(qyqhnjuvrk) = gehxfnparr zijzxbkxzw (jrbdvbxkvz, ylhrpjpoln - ilajiwwpzv) View more
NCT00819169 (CTgov)	Phase 1/2	Sarcoma \| Ovarian Cancer \| Neoplasm Metastasis \| Non-Small Cell Lung Cancer \| Colorectal Cancer \| Pancreatic Cancer	89	AMG 479+AMG 655 (Part 1 Cohort 1)	tzjqudkvnd(gjejzbkxse) = pwmpwmhrsy etytcyckzc (gfsmizawlq, xkeviktsyk - mfcldnhavx) View more	-	20 Aug 2024
				AMG 479+AMG 655 (Part 1 Cohort 2)	tzjqudkvnd(gjejzbkxse) = tizitlsktt etytcyckzc (gfsmizawlq, wwyuiokvrb - sznwmsyztt) View more
NCT01327612 (CTgov)	Phase 2	Sarcoma \| Carcinoid Tumor \| Neoplasm Metastasis \| Advanced Malignant Solid Neoplasm \| Non-Small Cell Lung Cancer \| Colorectal Cancer \| Lymphoma	12	Ganitumab (20050118: Ganitumab 20 mg/kg)	zlugganlpl(etamqdavar) = uufbkbobwf brbhzrrytd (qjdmurwodg, wxipwdwimv - idcsctytin) View more	-	21 Feb 2021
				Conatumumab (20050171: Conatumumab 0.45 mg/kg)	zlugganlpl(etamqdavar) = vnyllepgat brbhzrrytd (qjdmurwodg, cptvzdpqti - bxmlhomfda) View more
NCT00630786 (CTgov)	Phase 1/2	Rectal Cancer \| Colonic Cancer \| Metastatic Colorectal Carcinoma	53	Panitumumab+Conatumumab	kfophbsqrx(pwiieatkpz) = avzbmaleiy alqnzwpbjh (osryicqtdw, folpzithyp - oixudaasqw) View more	-	06 Feb 2014
ASCO2010	Phase 1	Solid tumor	9	Conatumumab	(skoorsicrx) = occurred in 2 pts biovxwvoog (baxgxbqtbt ) View more	-	20 May 2010
				AMG 479
ASCO2009	Phase 1	Non-Small Cell Lung Cancer	12	AMG 655 + PC	(yxzueicwgc) = evhvxxsptv xwmkexgjyx (lvbsrvkacd, 1.5 - 7.0)	-	20 May 2009