DESTINY-CRC02 Phase 2 Trial of ENHERTU® Initiated in Patients with HER2 Overexpressing Advanced Colorectal Cancer

MUNICH, Germany & BASKING RIDGE, NJ, USA I April 6, 2021 I Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca today announced that the first patient was dosed in DESTINY-CRC02, a global phase 2 trial evaluating the efficacy and safety of ENHERTU® (trastuzumab deruxtecan) in patients with HER2 overexpressing locally advanced, unresectable or metastatic colorectal cancer with progression following treatment with standard of care chemotherapy.

Colorectal cancer is the third most common cancer and second most common cause of cancer death globally.1 Approximately 20% of patients have metastatic disease at diagnosis, meaning the disease has spread to distant organs, and about 50-60% of patients initially diagnosed with early stage colorectal cancer will eventually develop metastases.2 There are currently no medicines approved to specifically treat HER2 overexpressing colorectal cancer, which affects approximately 2 to 5% of patients.3

“Patients with metastatic colorectal cancer often have limited treatment options following progression on standard of care therapy, making it important to understand new ways to treat these patients. Identifying patients with HER2 overexpression is an important area of research to further explore,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “Based on the encouraging data from the DESTINY-CRC01 phase 2 trial, we have initiated this second phase 2 study to further evaluate the potential of targeting HER2 with ENHERTU at the 5.4 mg/kg and 6.4 mg/kg doses in patients with HER2 overexpressing advanced colorectal cancer.”

About DESTINY-CRC02

DESTINY-CRC02 is a global, phase 2 trial evaluating the efficacy and safety of two doses (5.4 mg/kg or 6.4 mg/kg) of ENHERTU in patients with HER2 overexpressing BRAF wild-type, RAS wild-type or mutant locally advanced, unresectable or metastatic colorectal cancer with progression following treatment with standard of care chemotherapy. Previous treatments, if clinically indicated and not contraindicated, should include chemotherapy (fluoropyrimidine, oxaliplatin, and irinotecan); targeted therapy (anti-epidermal growth factor receptor (EGFR) treatment, (i.e. RAS wild-type); or, anti-vascular endothelial growth factor (VEGF) treatment); and/or immunotherapy (anti-programmed death-ligand 1 (PD-[L]-1) therapy, if tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high.

The study will be conducted in two stages. In stage 1, 80 patients will be randomized 1:1 to receive either 5.4 mg/kg or 6.4 mg/kg of ENHERTU administered every three weeks. After enrollment is completed in stage 1, 40 patients will be enrolled to the 5.4 mg/kg arm at stage 2. The primary endpoint is confirmed objective response rate (ORR) as assessed by blinded independent central review. Secondary endpoints include duration of response, disease control rate, clinical benefit ratio, investigator-assessed ORR, progression-free survival, overall survival, pharmacokinetics, patient reported outcomes and safety.

DESTINY-CRC02 will enroll approximately 120 patients at multiple sites in the Americas, Asia-Pacific, and Europe. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Overexpressing Colorectal Cancer

Colorectal cancer is the third most common cancer and second most common cause of cancer death globally.1 Approximately 20% of patients have metastatic disease at diagnosis, meaning the disease has spread to distant organs, and about 50-60% of patients initially diagnosed with early stage colorectal cancer will eventually develop metastases.2 Many patients with metastatic disease eventually progress on the current standard of care treatments.4

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers. Overexpression and amplification of HER2 occurs in approximately 2 to 5% of patients with colorectal cancer.3 Research indicates that HER2 amplification may be associated with resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy and shorter survival.5,6

About ENHERTU

ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed antibody drug conjugate (ADC). Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

ENHERTU (5.4 mg/kg) is approved under accelerated approval in the U.S, under conditional marketing authorization in the EU and the UK and under the conditional early approval system in Japan for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting based on the results from the DESTINY-Breast01 trial.

ENHERTU (6.4 mg/kg) is also approved in the U.S. and Japan for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

ENHERTU is not currently approved in the U.S. or any region worldwide for the treatment of colorectal cancer.

About the ENHERTU Clinical Development Program

A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

ENHERTU was recently highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the “ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers,” based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials.

In May 2020, ENHERTU received Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of patients with metastatic non-small cell lung cancer whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy.

About the Daiichi Sankyo and AstraZeneca Collaboration

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019, and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for manufacturing and supply of ENHERTU and datopotamab deruxtecan.

U.S. Important Safety Information for ENHERTU

Indications

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

  • Unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

    This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
  • Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

About Daiichi Sankyo Cancer Enterprise

The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by our DXd antibody drug conjugate (ADC) technology, our powerful research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.

About Daiichi Sankyo

Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical therapies to improve standards of care and address diversified, unmet medical needs of people globally by leveraging our world-class science and technology. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 15,000 employees around the world draw upon a rich legacy of innovation and a robust pipeline of promising new medicines to help people. In addition to a strong portfolio of medicines for cardiovascular diseases, under the Group’s 2025 Vision to become a “Global Pharma Innovator with Competitive Advantage in Oncology,” Daiichi Sankyo is primarily focused on providing novel therapies in oncology, as well as other research areas centered around rare diseases and immune disorders. For more information, please visit: www.daiichisankyo.com.

References:

1 World Health Organization. Cancer Factsheet. Accessed February 2021.

2 Jeong JH, et al. Clin Colorectal Cancer. 2017;16(3):e147-e152.

3 Siena S, et al. Ann Oncol. 2018;29:1108–1119.

4 Holch J, et al. Visc Med. 2016;32:178-183

5 Martin V, et al. Br J Cancer. 2013;108(3):668-675.

6 Wang X, et al. World J Gastrointest Oncol. 2019;11(4):335-347.

SOURCE: AstraZeneca

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