Delving into the Latest Updates on Duligotuzumab(Genentech, Inc.) with Synapse

Overview

Basic Info

Drug Type

Bispecific antibody

Synonyms

Anti-HER3/EGFR DAF, Duligotuzumab, Duligotuzumab (USAN)

+ [4]

Target

EGFR x HER3

Mechanism

EGFR antagonists(Epidermal growth factor receptor erbB1 antagonists), HER3 antagonists(Receptor tyrosine-protein kinase erbB-3 antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersRespiratory Diseases

Active Indication-

Inactive Indication

KRAS Wild-type Colorectal CancerLocally Advanced Malignant Solid NeoplasmNon-small cell lung cancer stage II+ [1]

Originator Organization

Genentech, Inc.

Active Organization-

Inactive Organization

Genentech, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 194728L

Source: *****

Sequence Code 9613449H

Source: *****

This open-label, multicenter, global Phase Ib study will evaluate the safety, tolerability and pharmacokinetics of intravenous (IV) dosing of MEHD7945A in combination with oral dosing of cobimetinib in patients with locally advanced or metastatic solid tumors that carry a Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutation and for which standard therapies do not exist, have proven ineffective or intolerable or are considered inappropriate. The study comprises a dose-escalation (Stage 1) and an indication-specific cohort expansion stage (Stage 2).

Start Date01 Nov 2013

Sponsor / Collaborator

Genentech, Inc.

NCT01911598

/ CompletedPhase 1

A Phase 1b Open-Label Study of the Safety and Pharmacokinetics of MEHD7945A in Combination With Either Cisplatin and 5-FU or Paclitaxel and Carboplatin in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

This open-label, multicenter study will evaluate the safety, tolerability, and pharmacokinetics of MEHD7945A in combination with chemotherapy (either cisplatin plus 5-FU or carboplatin plus paclitaxel) in participants with previously untreated R/M SCCHN. There are two stages for each arm in this study: a Dose-limiting Toxicity (DLT)-evaluation stage (Stage I) and a cohort-expansion stage (Stage II). In Stage I, DLTs will be assessed during a DLT Assessment Window of 21 days (i.e., Cycle 1 Day 1 through Cycle 1 Day 21) for both arms. In Stage II, participants will be enrolled to further characterize the safety, pharmacokinetics, and anti-tumor activity of MEHD7945A in combination with cisplatin + 5-FU or carboplatin + paclitaxel at the identified recommended Phase II dose.

Start Date19 Sep 2013

Sponsor / Collaborator

Genentech, Inc.

NCT01652482

/ CompletedPhase 2

A Phase II, Multicenter, Open-Label, Randomized Study Evaluating the Efficacy and Safety of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI in Second Line in Patients With KRAS Wildtype Metastatic Colorectal Cancer

This open-label, randomized, multicenter, Phase 2 study will evaluate the safety and efficacy of MEHD7945A when combined with FOLFIRI (folinic acid [leucovorin], 5-fluorouracil [5-FU], and irinotecan) chemotherapy as compared to cetuximab plus FOLFIRI in participants with Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type mCRC who have progressed after first-line oxaliplatin-containing chemotherapy for metastatic disease. Participants will be randomized to receive FOLFIRI chemotherapy plus either MEHD7945A or cetuximab. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Start Date01 Oct 2012

Sponsor / Collaborator

Genentech, Inc.

100 Clinical Results associated with Duligotuzumab(Genentech, Inc.)

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100 Translational Medicine associated with Duligotuzumab(Genentech, Inc.)

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100 Patents (Medical) associated with Duligotuzumab(Genentech, Inc.)

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18

Literatures (Medical) associated with Duligotuzumab(Genentech, Inc.)

01 Apr 2020·International journal of radiation oncology, biology, physicsQ2 · MEDICINE

Higher Anti-Tumor Efficacy of the Dual HER3-EGFR Antibody MEHD7945a Combined with Ionizing Irradiation in Cervical Cancer Cells

Q2 · MEDICINE

Article

Author: Henri-Alexandre Michaud ; Thierry Chardès ; Véronique Garambois ; Sylvain Demontoy ; Laura Bourillon ; André Pèlegrin ; David Azria ; Florence Boissière-Michot ; Alexandre Zampieri ; Hélène Perrochia ; Julien Fraisse ; Nathalie Bonnefoy ; Gauthier Rathat ; Céline Bourgier ; Christel Larbouret ; Alexis Lenglet ; Marta Jarlier ; Diego Tosi

PURPOSE:

The outcome of locally advanced cervical cancer (LACC) is dismal. Biomarkers are needed to individualize treatments and to improve patient outcomes. Here, we investigated whether coexpression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) could be an outcome prognostic biomarker, and whether targeting both EGFR and HER3 with a dual antibody (MEHD7945A) enhanced ionizing radiation (IR) efficacy.

METHODS AND MATERIALS:

Expression of EGFR and HER3 was evaluated by immunohistochemistry in cancer biopsies (n = 72 patients with LACC). The antitumor effects of the MEHD7945A and IR combotherapy were assessed in 2 EGFR- and HER3-positive cervical cancer cell lines (A431 and CaSki) and in A431 cell xenografts. The mechanisms involved in tumor cell radiosensitization were also studied. The interaction of MEHD7945A, IR, and cisplatin was evaluated using dose-response matrix data.

RESULTS:

EGFR and HER3 were coexpressed in only in 7 of the 22 biopsies of FIGO IVB cervix cancer. The median overall survival was 14.6 months and 23.1 months in patients with FIGO IVB tumors that coexpressed or did not coexpress EGFR and HER3, respectively. In mice xenografted with A431 (squamous cell carcinoma) cells, MEHD7945A significantly increased IR response by reducing tumor growth and increasing cleaved caspase-3 expression. In A431 and CaSki cells, the combotherapy increased DNA damage and cell death, particularly immunogenic cell death, and decreased survival by inhibiting the MAPK and AKT pathways. An additive effect was observed when IR, MEHD7945A, and cisplatin were combined.

CONCLUSIONS:

Targeting EGFR and HER3 with a specific dual antibody enhanced IR efficacy. These preliminary results and the prognostic value of EGFR and HER3 coexpression should be confirmed in a larger sample.

15 May 2018·Clinical cancer research : an official journal of the American Association for Cancer ResearchQ1 · MEDICINE

Phase II Study of the Dual EGFR/HER3 Inhibitor Duligotuzumab (MEHD7945A) versus Cetuximab in Combination with FOLFIRI in Second-Line RAS Wild-Type Metastatic Colorectal Cancer

Q1 · MEDICINE

Article

Author: Sufan, Roxana I. ; Hanley, William D. ; Jackson, Christopher ; Bridgewater, John ; Burge, Matthew E. ; Findlay, Michael P. ; Coveler, Andrew L. ; Penuel, Elicia M. ; Ganju, Vinod ; Jeffery, Mark ; Amatu, Alessio ; Pirzkall, Andrea ; Hidalgo, Manuel ; Tabernero, Josep ; Bartolomeo, Maria Di ; Kapp, Amy V. ; Hill, Andrew G. ; Samuel, Leslie ; Alfonso, Pilar Garcia ; Karthaus, Meinolf ; McCall, Bruce B.

Abstract:

Purpose: Duligotuzumab is a dual-action antibody directed against EGFR and HER3.Experimental Design: Metastatic colorectal cancer (mCRC) patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors.Results: Of 134 randomly assigned patients, 98 had RAS ex2/3 wild-type. Duligotuzumab provided no progression-free survival (PFS) or overall survival (OS) benefit compared with cetuximab, although there was a trend for a lower objective response rate (ORR) in the duligotuzumab arm. No relationship was seen between PFS or ORR and ERBB3, NRG1, or AREG expression. There were fewer skin rash events for duligotuzumab but more diarrhea. Although the incidence of grade ≥3 AEs was similar, the frequency of serious AEs was higher for duligotuzumab.Conclusions: Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with RAS exon 2/3 wild-type mCRC compared with cetuximab + FOLFIRI. Clin Cancer Res; 24(10); 2276–84. ©2018 AACR.

01 Oct 2017·ANNALS OF ONCOLOGY

Combination of duligotuzumab, anti HER3 antibody or taselisib, PI3K INhibitor with trastuzumab shows synergetic antitumoral activity in HER2 positive gastric cancer cells

Article

Author: Ciardiello, F. ; Savastano, B ; Orditura, M. ; De Vita, F. ; Savastano, B. ; Pompella, L ; Ciardiello, F ; Laterza, M M ; Petrillo, A. ; Morgillo, F. ; De Vita, F ; Pappalardo, A. ; Laterza, M.M. ; Morgillo, F ; Ciaramella, V. ; Orditura, M ; Tirino, G ; Belli, V. ; Petrillo, A ; Pompella, L. ; Ciaramella, V ; Belli, V ; Tirino, G. ; Pappalardo, A

100 Deals associated with Duligotuzumab(Genentech, Inc.)

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External Link

KEGG	Wiki	ATC	Drug Bank
D11750	Duligotuzumab(Genentech, Inc.)	-	DB12142

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
KRAS Wild-type Colorectal Cancer	Phase 2	US	Genentech, Inc.	01 Oct 2012
KRAS Wild-type Colorectal Cancer	Phase 2	AU	Genentech, Inc.	01 Oct 2012
KRAS Wild-type Colorectal Cancer	Phase 2	BE	Genentech, Inc.	01 Oct 2012
KRAS Wild-type Colorectal Cancer	Phase 2	FR	Genentech, Inc.	01 Oct 2012
KRAS Wild-type Colorectal Cancer	Phase 2	DE	Genentech, Inc.	01 Oct 2012
KRAS Wild-type Colorectal Cancer	Phase 2	IT	Genentech, Inc.	01 Oct 2012
KRAS Wild-type Colorectal Cancer	Phase 2	NZ	Genentech, Inc.	01 Oct 2012
KRAS Wild-type Colorectal Cancer	Phase 2	RO	Genentech, Inc.	01 Oct 2012
KRAS Wild-type Colorectal Cancer	Phase 2	ES	Genentech, Inc.	01 Oct 2012
KRAS Wild-type Colorectal Cancer	Phase 2	GB	Genentech, Inc.	01 Oct 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01986166 (Pubmed \| Oncologist) Manual	Phase 1	Neoplasms KRAS Mutation	23	Cobimetinib+Duligotuzumab	vmdvxmcmrn(wnizukllnh) = gvrxfbipni wuhznezhpy (ymrsyswbuj ) View more	Negative	01 Sep 2017
NCT01911598 (Pubmed \| Cancer) Manual	Phase 1	Squamous Cell Carcinoma of Head and Neck First line	24	cisplatin+fluorouracil+duligotuzumab	bzqmimeyde(vktmbguvll) = xezakglrnu zlacuorxbn (smanhelzds )	Positive	15 Dec 2016
NCT01911598 (Pubmed \| Cancer) Manual	Phase 1	Squamous Cell Carcinoma of Head and Neck First line	24	carboplatin+paclitaxel+duligotuzumab	bzqmimeyde(vktmbguvll) = ylfluognid zlacuorxbn (smanhelzds )	Positive	15 Dec 2016
NCT01577173 (MEHGAN, Pubmed \| Front Oncol) Manual	Phase 2	Squamous Cell Carcinoma NRG1 \| ERBB3 \| HPV	121	duligotuzumab	ctzcuuenkp(ndnydauyfk) = rdkdouscjh ivbrddezpf (veawkvewhd ) View more	Negative	31 Oct 2016
NCT01577173 (MEHGAN, Pubmed \| Front Oncol) Manual	Phase 2	Squamous Cell Carcinoma NRG1 \| ERBB3 \| HPV	121	Cetuximab	ctzcuuenkp(ndnydauyfk) = iirelaqdfw ivbrddezpf (veawkvewhd ) View more	Negative	31 Oct 2016
ASCO2012	Phase 1	Glandular and Epithelial Neoplasms	-	MEHD7945A (MEHD)	dsxgobpwmr(iimszuuirp) = clfsmiqdbe givlpvnvpt (wxdbfybkyz ) View more	-	20 May 2012