Delving into the Latest Updates on Futuximab/Modotuximab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Modotuximab/futuximab

+ [7]

Target

EGFR

Mechanism

EGFR antagonists(Epidermal growth factor receptor erbB1 antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersNervous System Diseases+ [1]

Active Indication

Solid tumorMetastatic Colorectal CarcinomaGlioblastoma

Inactive Indication

Advanced Malignant Solid NeoplasmCarcinomametastatic non-small cell lung cancer+ [3]

Originator Organization

Active Organization

+ [2]

Inactive Organization

EMD Serono, Inc.Merck KGaA

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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A Randomised, Open-label, Multi-centre, Two-arm Phase 3 Study Comparing Futuximab/Modotuximab in Combination With Trifluridine/Tipiracil to Trifluridine/Tipiracil Single Agent With a Safety Lead-In Part in Participants With KRAS/NRAS and BRAF Wild Type Metastatic Colorectal Cancer Previously Treated With Standard Treatment and Anti-EGFR Therapy

This is a randomized phase III study with a safety lead-in part in patients with KRAS/ NRAS and BRAF Wild Type metastatic colorectal cancer who have previously received treatment with oxaliplatin, irinotecan, fluoropyrimidines, anti-VEGF agents and anti-EGFR antibodies. The main objective of the safety lead-in part is to assess safety and tolerability of futuximab/modotuximab in combination with trifluridine/tipiracil. The primary objective of the phase III part is to compare Overall Survival of futuximab/modotuximab in combination with trifluridine/tipiracil vs trifluridine/tipiracil monotherapy in patients with tumours that are KRAS/NRAS and BRAF wild-type (WT).

Start Date21 Apr 2022

Sponsor / Collaborator

Institut de Recherches Intern Servier

[+1]

NCT03717038 / WithdrawnPhase 3

A Phase 3, Randomized, Open-Label, Multicenter Trial of Sym004 Versus Trifluridine/Tipiracil (TAS-102) in Patients With Chemotherapy-Refractory or Relapsed Metastatic Colorectal Carcinoma and Acquired Resistance to Anti-EGFR Monoclonal Antibody Therapy

This is a Phase 3, randomized, open-label, 2-arm trial designed to evaluate overall survival (OS) following treatment with Sym004, an investigational medicinal product (IMP), versus TAS-102 (trifluridine/tipiracil), a comparator (control) agent.

Start Date01 Feb 2019

Sponsor / Collaborator

Symphogen A/S

NCT03549338 / TerminatedPhase 2

A Ph2, Randomized, Open-Label, Multicenter, Three-Arm Trial of Sym004 Versus Each of Its Component Futuximab and Modotuximab, in Patients With Chemotherapy-Refractory Metastatic Colorectal Carcinoma and Acquired Resistance to Anti-EGFR mAb

This is a Phase 2, randomized, open-label, 3-arm trial in the ratio of 1:1:1 to either Sym004 (Arm A) versus each of its component monoclonal antibodies (mAbs), futuximab (Arm B) or modotuximab (Arm C), in genomically-selected patients with chemotherapy-refractory metastatic colorectal carcinoma (mCRC) and acquired resistance to anti-epidermal growth factor receptor (anti-EGFR) mAb therapy. The study is designed to evaluate the relative antitumor activity of each agent as assessed by imaging studies performed after 8 weeks of treatment.

Start Date29 Nov 2018

Sponsor / Collaborator

Symphogen A/S

100 Clinical Results associated with Futuximab/Modotuximab

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100 Translational Medicine associated with Futuximab/Modotuximab

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100 Patents (Medical) associated with Futuximab/Modotuximab

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19

Literatures (Medical) associated with Futuximab/Modotuximab

02 Jun 2024·Expert Opinion on Biological Therapy

Progress in second-line antibody therapies for advanced esophageal squamous cell carcinoma

Review

Author: Yamamoto, Shun ; Ogura, Nozomu ; Kato, Ken

INTRODUCTIONThe prognosis of advanced esophageal squamous cell carcinoma (ESCC) is poor. Although cytotoxic drugs have been widely used in advanced ESCC, several antibody agents have recently been reported to be effective.AREAS COVEREDNivolumab and pembrolizumab are anti-PD-1 antibodies that improve immunosuppression by binding to programmed death-1 (PD-1), leading to an antitumor effect. Randomized phase III trials have found these immune checkpoint inhibitors (ICIs) to be effective as second-line treatment. ATTRACTION-3, which compared nivolumab monotherapy with taxane monotherapy in patients with previously treated advanced ESCC, reported prolonged overall survival in the nivolumab group. KEYNOTE-181 found that overall survival was longer in patients with PD-L1-positive ESCC who received second-line treatment with pembrolizumab than in those who received chemotherapy. Sym004 and amivantamab are antibodies that target the epidermal growth factor receptor and have demonstrated efficacy in the treatment of other tumors in recent phase I studies. Furthermore, clinical trials on antibody-drug conjugates such as enfortumab vedotin and DS-7300 for solid tumors are currently ongoing.EXPERT OPINIONThe standard first-line treatments for patients with advanced ESCC contain ICIs. Therefore, drugs with different mechanisms of action that can overcome resistance to ICIs are needed as second-line or later-line treatments to improve clinical outcomes in these patients.

01 Feb 2020·Journal of Pharmacokinetics and PharmacodynamicsQ3 · MEDICINE

Population pharmacokinetics and covariate analysis of Sym004, an antibody mixture against the epidermal growth factor receptor, in subjects with metastatic colorectal cancer and other solid tumors

Q3 · MEDICINE

Article

Author: Kragh, Michael ; Kopetz, Scott ; Schoemaker, Rik ; Wade, Janet R ; Tabernero, Josep ; Alifrangis, Lene ; Hald, Rikke ; Skartved, Niels J ; Montagut, Clara

Sym004 is an equimolar mixture of two monoclonal antibodies, futuximab and modotuximab, which non-competitively block the epidermal growth factor receptor (EGFR). Sym004 has been clinically tested for treatment of solid tumors. The present work characterizes the non-linear pharmacokinetics (PK) of Sym004 and its constituent antibodies and investigates two types of covariate models for interpreting the interindividual variability of Sym004 exposure. Sym004 serum concentration data from 330 cancer patients participating in four Phase 1 and 2 trials (n = 247 metastatic colorectal cancer, n = 87 various types advanced solid tumors) were pooled for non-linear mixed effects modeling. Dose regimens of 0.4-18 mg/kg Sym004 dosed by i.v. infusion weekly or every 2nd week were explored. The PK profiles for futuximab and modotuximab were parallel, and the parameter values for their population PK models were similar. The PK of Sym004 using the sum of the serum concentrations of futuximab and modotuximab was well captured by a 2-compartment model with parallel linear and saturable, Michaelis-Menten-type elimination. The full covariate model including all plausible covariates included in a single step showed no impact on Sym004 exposure of age, Asian race, renal and hepatic function, tumor type and previous anti-EGFR treatments. The reduced covariate model contained statistically and potentially clinically significant influences of body weight, albumin, sex and baseline tumor size. Population PK modeling and covariate analysis of Sym004 were feasible using the sum of the serum concentrations of the two constituent antibodies. Full and reduced covariate models provided insights into which covariates may be clinically relevant for dose modifications and thus may need further exploration.

01 Dec 2019·Journal of Experimental & Clinical Cancer ResearchQ1 · MEDICINE

Combined blockade of MEK and PI3KCA as an effective antitumor strategy in HER2 gene amplified human colorectal cancer models

Q1 · MEDICINE

ArticleOA

Author: Matrone, Nunzia ; Trusolino, Livio ; Morgillo, Floriana ; Ciardiello, Fortunato ; Troiani, Teresa ; Martinelli, Erika ; Cottino, Francesca ; Bertotti, Andrea ; Ciardiello, Davide ; Migliardi, Giorgia ; Bracale, Umberto ; Napolitano, Stefania ; Belli, Valentina ; De Falco, Vincenzo ; Giunta, Emilio Francesco

BACKGROUNDTargeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy is an effective treatment for patients with RAS wild-type metastatic colorectal cancer (mCRC). However, only a small percentage of mCRC patients receive clinical benefits from anti-EGFR therapies, due to the development of resistance mechanisms. In this regard, HER2 has emerged as an actionable target in the treatment of mCRC patients with resistance to anti-EGFR therapy.METHODSWe have used SW48 and LIM1215 human colon cancer cell lines, quadruple wild-type for KRAS, NRAS, BRAF and PI3KCA genes, and their HER2-amplified (LIM1215-HER2 and SW48-HER2) derived cells to perform in vitro and in vivo studies in order to identify novel therapeutic strategies in HER2 gene amplified human colorectal cancer.RESULTSLIM1215-HER2 and SW48-HER2 cells showed over-expression and activation of the HER family receptors and concomitant intracellular downstream signaling including the pro-survival PI3KCA/AKT and the mitogenic RAS/RAF/MEK/MAPK pathways. HER2-amplified cells were treated with several agents including anti-EGFR antibodies (cetuximab, SYM004 and MM151); anti-HER2 (trastuzumab, pertuzumab and lapatinib) inhibitors; anti-HER3 (duligotuzumab) inhibitors; and MEK and PI3KCA inhibitors, such as refametinib and pictilisib, as single agents and in combination. Subsequently, different in vivo experiments have been performed. MEK plus PI3KCA inhibitors treatment determined the best antitumor activity. These results were validated in vivo in HER2-amplified patient derived tumor xenografts from three metastatic colorectal cancer patients.CONCLUSIONSThese results suggest that combined therapy with MEK and PI3KCA inhibitors could represent a novel and effective treatment option for HER2-amplified colorectal cancer.

100 Deals associated with Futuximab/Modotuximab

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Phase 3	FR	Taiho Oncology, Inc.	30 Jan 2022
Solid tumor	Phase 3	FR	Servier Group	30 Jan 2022
Squamous cell carcinoma of head and neck metastatic	Phase 2	DE	Symphogen A/S	01 Jul 2011
Squamous cell carcinoma of head and neck metastatic	Phase 2	FR	Symphogen A/S	01 Jul 2011
Carcinoma	Preclinical	-	Symphogen A/S	01 Feb 2019
Advanced Malignant Solid Neoplasm	Preclinical	US	Symphogen A/S	01 Mar 2010
Metastatic Colorectal Carcinoma	Discovery	-	Symphogen A/S	01 Feb 2019
Metastatic Colorectal Carcinoma	Discovery	-	Symphogen A/S	01 Feb 2019
Advanced Malignant Solid Neoplasm	Discovery	BE	Symphogen A/S	01 Mar 2010
Advanced Malignant Solid Neoplasm	Discovery	ES	Symphogen A/S	01 Mar 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05223673 (COLSTAR, CTgov)	Phase 3	RAS/BRAF Wild Type Colorectal Cancer \| Metastatic Colorectal Carcinoma	7	Futuximab/modotuximab+Trifluridine/Tipiracil	hxocxmcqhb(usoqxhhdmt) = gkrzqwgdpk kexwieyhls (egdyafjmhb, bfdrxydgau - sktojikmjj) View more	-	05 Mar 2024
NCT02540161 (CTgov)	Phase 2	Recurrent Glioblastoma	43	Sym004 - 18 mg/kg (Non-bevacizumab Failures - 18 mg/kg)	uvaujiqfjw(jcxahiojgj) = gjitkiuryr qxhxyrltwa (yfslycwmea, johrsniegs - pwxqxajbgp) View more	-	24 Jul 2020
				Sym004 - 18 mg/kg (Bevacizumab Failures - 18 mg/kg)	uvaujiqfjw(jcxahiojgj) = kohrxidsqo qxhxyrltwa (yfslycwmea, ussmdyvqix - cszdyruuwn) View more
NCT03549338 (CTgov)	Phase 2	Metastatic Colorectal Carcinoma \| Carcinoma	2	Sym004 (Arm A (Sym004))	sucmagftud(wfeyvdtkjp) = iydqutcbzr qijsstloix (hvkhbbobpn, kbchyeegzc - bsewzblwmy) View more	-	14 Jan 2020
				Futuximab (Arm B (Futuximab))	sucmagftud(wfeyvdtkjp) = biqmusimls qijsstloix (hvkhbbobpn, smeclszkiw - mdluhjzoyb) View more
NCT02568046 (CTgov)	Phase 1/2	Metastatic Colorectal Carcinoma	10	FOLFIRI+Sym004 (Dose Level 1: Sym004 12 mg/kg + FOLFIRI)	fdbmgeboid(eotlzwkghz) = qcnygpirtv ephzmpmasc (djrvujfwmy, ehatlirnei - bajelbkihe) View more	-	09 Jan 2019
				FOLFIRI+Sym004 (Dose Level -1: Sym004 9 mg/kg + FOLFIRI)	fdbmgeboid(eotlzwkghz) = vlblobbdsd ephzmpmasc (djrvujfwmy, ckhcrtzekj - rfapgehkdc) View more
NCT02083653 (CTgov)	Phase 2	Metastatic Colorectal Carcinoma	254	Sym004 (12 mg/kg) (Arm A: Sym004 (12 mg/kg))	ojqhlcohuh(gmwrbpitrp) = gkcbkipvhx dkviqjddqj (xdikvmtylc, pqfgejvnpy - zjvcfqdvdw) View more	-	24 Dec 2018
				Sym004 (9/6 mg/kg) (Arm B: Sym004 (9/6 mg/kg))	ojqhlcohuh(gmwrbpitrp) = tvvbrcpnlq dkviqjddqj (xdikvmtylc, vwjizoljec - gzzomsszul) View more
NCT01955473 (Pubmed) Manual	Phase 1	Solid tumor	51	Sym004 (expansion Part)	(zycypgqzpb) = No dose-limiting toxicities were observed in Part A. dbhblrmaoj (wzqmdxyvwi )	Positive	01 Oct 2018
				Sym004
Phase 2b trial (ASCO2018)	Phase 2	Metastatic Colorectal Carcinoma	254	Sym004	(ehgklqrbpz) = ijfhgvwnvn nyyrmqnhqz (xzflumzvrx )	Positive	01 Jun 2018
NCT01117428 (CTgov)	Phase 1/2	Advanced Malignant Solid Neoplasm \| Metastatic Colorectal Carcinoma	111	Sym004 (Part A: Dose Escalation)	nyxupdnvtf(euowoylkel) = gkfqkpvuxj shlsdpuqnz (fyqoxlvyls, ydchlbxinc - hpcsosxhcc) View more	-	12 Jul 2017
				Sym004 (Part B: Dose Expansion Cohort)	nyxupdnvtf(euowoylkel) = sdyxfemuau shlsdpuqnz (fyqoxlvyls, nuwyxwbfob - inhhzcdhsj) View more
NCT01955473 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm	51	Sym004 (Part A: Sym004 6 mg/kg)	pdyainbqob(scdgpnjvko) = lohqfkniaq dcirolsoky (rvrmsybdsg, awpqwkaqab - uemzkpkfde) View more	-	07 Mar 2017
				Sym004 (Part A: Sym004 9/6 mg/kg)	pdyainbqob(scdgpnjvko) = xltohxosmv dcirolsoky (rvrmsybdsg, gpoqzdpaaz - iessjljxvm) View more
NCT02083679 (CTgov)	Phase 1	metastatic non-small cell lung cancer	15	Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine (Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine)	xgtuhxjptr(zsgeixmfsy) = qdchoczlvi sxjtbxwbuq (lhunvqkwxu, ssnhnibxwi - kedfcavwzp) View more	-	25 Oct 2016
				Sym004+Cisplatin+Pemetrexed (Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed)	xgtuhxjptr(zsgeixmfsy) = depzkacieq sxjtbxwbuq (lhunvqkwxu, nlhxajceth - zyxdsqebyp) View more