duligotuzumab (MEHD7945A) / Roche - LARVOL DELTA

Higher Anti-Tumor Efficacy of the Dual HER3-EGFR Antibody MEHD7945a Combined with Ionizing Irradiation in Cervical Cancer Cells. (PubMed, Int J Radiat Oncol Biol Phys) - "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."

Clinical • Journal • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Squamous Cell Carcinoma

Biomarker evaluation in a randomized phase 2 study of MEHD7945A (MEHD) versus cetuximab (Cet) in ≥2 line recurrent/metastatic (R/M) squamous cell carcinomas of the head and neck (SCCHN) [MEHGAN] (AACR 2015) - Presentation time: Monday, Apr 20, 2015, 8:00 AM -12:00 PM; Abstract #1553; P2; N=121; NCT01577173; " Key findings include: 1) Most patients with CT RECIST responses on either treatment arm had higher (≥ median) tumor expression levels of NRG1 as measured by qRT-PCR 2) EGFR ligands such as amphiregulin were co-expressed with NRG1, consistent with preclinical analysis in an independent panel of SCCHN tumor samples (Genentech data on file)."

Biomarker • P2 data • Head and Neck Cancer • Oncology

A Study of MEHD7945A Versus Cetuximab in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of The Head And Neck (clinicaltrials.gov) - P2; N=122; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed; Trial primary completion date: Nov 2015 ➔ Jun 2015

Trial completion • Trial primary completion date • Biosimilar • Head and Neck Cancer • Oncology

A Study of MEHD7945A in Combination With Cisplatin and 5-FU or Paclitaxel and Carboplatin on Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P1b; N=24; Active, not recruiting; Sponsor: Genentech, Inc.; Phase classification: P1 ➔ P1b

Phase classification • Biosimilar • Head and Neck Cancer • Oncology

A Study of MEHD7945A in Combination With Cisplatin and 5-FU or Paclitaxel and Carboplatin on Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P1; N=24; Active, not recruiting; Sponsor: Genentech, Inc.; Trial primary completion date: May 2016 ➔ Dec 2016

Trial primary completion date • Biosimilar • Head and Neck Cancer • Oncology

Human pharmacokinetic (PK) characterization of the novel dual-action anti-HER3/EGFR antibody MEHD7945A (MEHD) in patients with refractory/recurrent epithelial tumors (ASCO 2012) - Presentation time: Mon, Jun 4; 8:00 AM - 12:00 PM; Anticipated presentation at ASCO 2012

Anticipated data presentation • Oncology

Human pharmacokinetic (PK) characterization of the novel dual-action anti-HER3/EGFR antibody MEHD7945A (MEHD) in patients with refractory/recurrent epithelial tumors (ASCO 2012) - Presentation time: Monday June 4, 8:00 AM - 12:00 PM; P1, N=1,000; In the noncompartmenal analysis, the apparent clearance (CL) decreased in a dose-dependent fashion (about 40 to 9.9 mL/day/kg from 1 to 30 mg/kg) and approached linearity at doses >10 mg/kg (q2w); In the population analysis, the PK profile of MEHD was well described by a two compartment model with linear and nonlinear clearance

PK data • Oncology

Combined blockade of PI3K/AKT and EGFR/HER3 enhances anti-tumor activity in triple negative breast cancer (SABCS 2012) - “...GDC0068 and GDC0941 treatment resulted in variable inhibition of cell viability, with IC50s ranging from 170 nM to >1 µM across all TNBC cell lines. Under full-serum (10% FBS) conditions, MEHD7945A led to a very mild decrease in cell viability in vitro. Combination treatments were modestly more effective than monotherapy in vitro. In vivo, MEHD7945, GDC0941 and GDC0068 showed variable delay in tumor growth whereas combination of MEHD7945A with either GDC0068 or GDC0941 was superior to single agent treatment...”

Preclinical • Breast Cancer • Oncology

A Study of MEHD7945A in Combination With Cisplatin and 5-FU or Paclitaxel and Carboplatin on Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P1; N=24; Active, not recruiting; Sponsor: Genentech, Inc.; Recruiting -> Active, not recruiting ; N=30 -> 24

Enrollment change • Enrollment closed • Biosimilar • Head and Neck Cancer • Oncology

A study of MEHD7945A + FOLFIRI versus cetuximab + FOLFIRI in second line in patients with KRAS wild-type metastatic colorectal cancer (clinicaltrials.gov) - P2, N=120 -> 135; Recruiting -> Active, not recruiting. 

Enrollment change • Enrollment closed • Colorectal Cancer • Oncology

Role and mechanisms of resistance of epidermal growth factor receptor antagonists in the treatment of colorectal cancer. (PubMed) - "Although the negative predictive role of RAS and possibly BRAF mutations has already been established, more comprehensive efforts are needed to optimize the use of these drugs. At the same time, understanding the underlying biology will help basic scientists to develop new compounds able to overcome both primary and acquired resistance and help clinical researchers to test novel drugs within adequately designed trials whose results eventually are expected to reshape the overall treatment strategy."

Journal • Biosimilar • Colorectal Cancer • Multiple Myeloma • Oncology

Roche: HY 2014 Results (Roche) - Anticipated NME submission in US for metastatic epithelial tumors in 2017 or later; Anticipated NME submission in EU for metastatic epithelial tumors in 2017 or later

Anticipated EU regulatory • Anticipated NDA • Oncology

A phase I study of MEHD7945A (MEHD), a first-in-class HER3/EGFR dual-action antibody, in patients (pts) with refractory/recurrent epithelial tumors: Expansion cohorts (ASCO 2012) - Presentation time: Mon, Jun 4; 8:00 AM - 12:00 PM; Anticipated presentation at ASCO 2012

Anticipated P1 data presentation • Oncology

Phase 1b study of MEHD7945A (MEHD) plus cisplatin/fluorouracil (cis/5FU) or carboplatin/paclitaxel (carbo/pac) for 1st-line treatment of recurrent/metastatic squamous cell carcinoma of head and neck (RMSCCHN) (ESMO 2014) - Presentation time: 28.09.2014, 13:00 - 14:00; Abstract #989PD; P1b, N=18; NCT01911598; Sponsor: Genentech; "Preliminary MEHD PK in both arms was similar to single-agent MEHD profile. In 12 pts with on-treatment tumor assessments, best responses were 9 (75%) PR (4 confirmed) [Arm A: 4; Arm B: 5; HPV: 2+, 5-, 2 unknown], and 3 (25%) stable disease [Arm A: 1; Arm B: 2]; after data cutoff 2 pts were reported with CR."

P1 data • Head and Neck Cancer • Oncology

A phase I study of MEHD7945A (MEHD), a first -in-class HER3/EGFR dual-action antibody, in patients (pts) with refractory/recurrent epithelial tumors: Expansion cohorts (ASCO 2012) - Presentation time: Monday June 4, 8:00 AM to 12:00 PM; P1, N=36; Study ID GO00765; PK data are consistent with human anti-EGFR antibodies; No related G≥3 AEs have been observed; Common related G1/2 AEs included rash/dermatitis (53%), diarrhea (36%), fatigue (22%), paronychia (19%), dry skin, nausea, and decreased appetite (all 17%), asthenia and stomatitis/oral pain (all 14%)

P1 data • Oncology

Phase II study of the dual EGFR/HER3 inhibitor duligotuzumab (MEHD7945A) vs. cetuximab in combination with FOLFIRI in RAS wild-type metastatic colorectal cancer. (PubMed, Clin Cancer Res) - "Duligotuzumab plus FOLFIRI did not appear to improve the outcomes in patients with RAS exon 2/3 wild-type mCRC compared to cetuximab + FOLFIRI."

Biomarker • Clinical • Combination therapy • Journal • P2 data

Imaging EGFR and HER3 through Zr-labeled MEHD7945A (Duligotuzumab). (PubMed, Sci Rep) - "Tumor accretion and whole body pharmacokinetics of Zr-MEHD7945A were established. Specificity of the probe for EGFR and/or HER3 was further examined."

IO Companion Diagnostic • Journal