Policy & Regulation
Daiichi Sankyo Forges Clinical Trial Collaboration with AstraZeneca to Evaluate Patritumab Deruxtecan in Combination with TAGRISSO in EGFR-Mutated Non-Small Cell Lung Cancer
11 August 2020 - - Japanese paharmaceutical group Daiichi Sankyo Company, Ltd. has entered into a clinical trial collaboration with British drugmaker AstraZeneca (LSE: AZN) (NYSE: AZN) to evaluate the combination of patritumab deruxtecan (U3-1402), a HER3 directed DXd antibody drug conjugate, and Tagrisso (osimertinib), an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with EGFR-mutated advanced or metastatic non-small cell lung cancer (NSCLC), the company said.

There are no HER3 directed therapies approved for the treatment of NSCLC or any cancer.

The frequency of HER3 overexpression in EGFR-mutated NSCLC has been reported to be as high as 75%, and there is evidence that HER3 expression may be associated with resistance to TKIs.

Under the terms of the agreement, Daiichi Sankyo will sponsor and conduct a multicenter, open-label, two-part phase 1 study evaluating patritumab deruxtecan and Tagrisso as both a first-line and second-line combination treatment in patients with advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation.

The first part of the study (dose escalation) will assess the safety and tolerability of different dosing combinations of patritumab deruxtecan and Tagrisso to determine the recommended combination dose.

The second part of the study (dose expansion) will include a first-line and second-line cohort that will further evaluate the anti-tumor activity and safety of the combination.

Patients enrolled in the first-line cohort will receive patritumab deruxtecan and TAGRISSO combination treatment, and patients in the second-line cohort will be randomized 1: 1 to receive treatment with patritumab deruxtecan alone or in combination with Tagrisso.

Up to 258 patients will be enrolled into the study, which will be conducted in North America, Europe, and Asia including Japan.

The primary study objectives for the dose escalation part of the study include the assessment of the safety and tolerability of patritumab deruxtecan and Tagrisso.

The primary objective for the dose expansion part of the study for both cohorts is the assessment of anti-tumor activity as measured by objective response rate and as assessed by independent central review.

Lung cancer is the most common cancer and is the leading cause of cancer mortality worldwide with an estimated 2.1 m new cases of lung cancer in 2018 and 1.8m deaths.

Non-small cell lung cancer (NSCLC) accounts for 80 to 85 % of all lung cancers.

Mutations in the epidermal growth factor receptor gene are among the most frequently observed genomic alterations in NSCLC, affecting approximately 14 to 30% of patients with NSCLC.

For patients with EGFR-mutated NSCLC, targeted therapy with EGFR TKIs offers higher response rates, overall survival and progression-free survival compared to chemotherapy.

However, most patients eventually develop resistance to the TKIs, and new treatment approaches including combination strategies designed to overcome TKI resistance are needed.

HER3 is a member of the EGFR family of tyrosine kinase receptors, which are associated with normal as well as aberrant cell proliferation and survival.

HER3 expression has been associated with an increased incidence of metastases and reduced survival in patients with NSCLC with expression frequency reported to be as high as 75%.

A majority of EGFR-mutated NSCLCs show some level of HER3 expression.

Currently, no HER3 directed therapies are approved for NSCLC or any cancer.

Patritumab deruxtecan (U3-1402) is one of three lead DXd antibody drug conjugates in the oncology pipeline of Daiichi Sankyo.

ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

Designed using Daiichi Sankyo's proprietary DXd ADC technology, patritumab deruxtecan is comprised of a human anti-HER3 antibody attached to a topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells that express HER3 as a cell surface antigen.

Patritumab deruxtecan is currently being evaluated in a phase 1 study in previously treated patients with metastatic or unresectable NSCLC. Patritumab deruxtecan is also being evaluated in a phase 1/2 study in patients with HER3 expressing metastatic breast cancer.

Patritumab deruxtecan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.
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