HER3 targets new ADC drugs! 13th Total/AstraZeneau Latest Collaboration: Patritumab deruxtecan and Tagrisso for the Treatment of Lung Cancer!

August 10, 2020 // -- Daiichi Sankyo has announced that it is working with AstraZeneca to enter a clinical trial to evaluate patritumab deruxtecan (U3-1402) in cooperation with Tagrisso (Terisha, generic name: osimertinib, Ohitinib) for patients with advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations.
patritumab deruxtecan is an antibody drug concatenation (ADC) that targets HER3 and is one of the three leading DXd ADC therapies in the first three total tumor lines, while Tagrisso is an epiderminent growth factor receptacle (EGFR) tyrosine kinase inhibitor (TKI).
, the two sides have signed a $6.9 billion and $6 billion immuno-oncology partnership on two other DXd ADC therapies (Enhertu, DS-1062) in the First Third Total Tumor Pipeline.
, no HER3 targeted therapy has been approved for NSCLC or any cancer treatment.
reported that her3 overexpression occurs up to 75 percent of the time in NSCLCs with EGFR mutations, and there is evidence that HER3 expression may be associated with tumor resistance to TKI.
The latest collaboration, under the terms of the agreement, Will sponsor and conduct a multi-center, open-label, two-part Phase I study evaluating patritumab deruxtecan and Tagrisso as first- and second-line combination therapies for patients with advanced or metastatic NSCLCs with EGFR exome 19 deficiency or L858R mutations."
study will be conducted in North America, Europe and Asia, including Japan, with 258 patients in the group. Dr Gilles Gallant, Vice President and Global Director of Research and Development at
First Third Co-oncology, said: "Most patients with NSCLC with EGFR-activated mutations or EGFR mutations overexpress HER3 proteins in cancer cells, and there is evidence that HER3 expression is a "passenger marker" for TKI resistance."
Clinical and preclinical data, as well as biomarker expression and resistance mechanism studies, support further evaluation of the patritumab deruxtecan and Tagrisso combinations for the treatment of EGFR mutant NSCLC patients who progress after receiving TKI (usually Gagrisso).
this clinical trial collaboration supports our goal of optimizing the development of patritumab deruxtecan in EGFR mutant metastatic NSCLC patients to further improve current standards of care.
first three are pleased to work with AstraZeneau on this important aspect of patritumab deruxtecan development.
"In this trial, we will explore a potential new approach to treating patients with advanced diseases: combining Tagrisso with HER3-oriented ADC therapy patritumab deruxtecan," said Cristian Massacesi, senior vice president and head of AstraZeneau's late-stage oncology research and development division.
this combined approach represents one of our strategies for dealing with tumor resistance.
we will continue to work with First Three in this area to maximize our research results.
" noteworthy is that AstraZeneira and First Three have already reached a huge partnership on two ADC drugs.
March 2019, the two sides signed a $6.9 billion immuno-oncology partnership to develop HER2-targeted ADC therapy Enhertu (trastuzumab deruxtecan, DS-8201) for treating cancer patients with various HER2 expression levels or HER2 mutations, including stomach, colorectal and lung cancers, and HER2 low-expression breast cancer.
In July 2020, the two sides signed a $6 billion immuno-oncology partnership to develop the targeted TROP2 ADC therapy DS-1062, which is currently in Phase I clinical treatment for non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC).
Enhertu, DS-1062, patritumab deruxtecan are the first and third generation of ADC drugs developed using DXd ADC technology, through a 4 peptide link to target the tumor cell surface-specific antigen human-sourced monoclonal antibodies (respectively: anti-HER2 monoantigens, anti-TROP 2 monoantrance, anti-HER3 monoantry (patritumab)) linked to a new topological isomerase 1 inhibitor exatecan derivative (DX-8951 derivative, DXd) can be targeted to deliver cytotoxic agents to cancer cells, compared to the usual chemotherapy, can reduce the total body exposure of cytotoxic agents.
December 2019, Enhertu received accelerated FDA approval for adults with HER2-positive metastatic breast cancer who have received 2 or more anti-HER2 medications for metastatic diseases.
, Enhertu is also under review by EU and Japanese regulators.
() Original source: Daiichi Sankyo Announces Clinical Trials with AstraZeneca to Evaluate Patritumab Deruxtecan (U3-1402) in Total with TAGRISSO in EGFR-Mutated Non-Small Cell Cell Cancer.