ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by
The
The FDA granted the BTD for the treatment of metastatic HER2 positive solid tumors based on results from the ongoing DESTINY-PanTumor02 phase 2 trial with supporting data from other trials in the ENHERTU clinical development program. Results from an interim analysis of DESTINY-PanTumor02 were presented as a late-breaking oral presentation at the 2023
'ENHERTU is the first HER2 directed therapy to demonstrate a potential benefit across a series of difficult-to-treat cancers and these designations are recognition of the continued potential of this innovative medicine,' said
'This is an important step in bringing ENHERTU to patients with a broad range of HER2 expressing solid tumors who currently face a poor prognosis,' said
ENHERTU has received seven BTDs and its designation in HER2 expressing metastatic solid tumors represents the first time ENHERTU has been granted this designation in a tumor agnostic setting. ENHERTU previously received BTDs for three indications in breast cancer, including HER2 low metastatic breast cancer, second-line HER2 positive metastatic breast cancer and later-line HER2 positive metastatic breast cancer. Two additional BTDs for ENHERTU were granted for HER2 (ERBB2) mutant metastatic non-small cell lung cancer (NSCLC) and HER2 positive metastatic gastric cancer.
About DESTINY-PanTumor02
DESTINY-PanTumor02 is a global, multicenter, multi-cohort, open-label phase 2 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) for the treatment of HER2 expressing tumors (IHC 3+ or IHC 2+), including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer and other tumors.
The primary efficacy endpoint of DESTINY-PanTumor02 is confirmed objective response rate (ORR) as assessed by investigator. Secondary endpoints include duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety, tolerability and pharmacokinetics.
DESTINY-PanTumor02 has enrolled 268 patients at multiple sites in
About DESTINY-CRC01
DESTINY-CRC01 is a global, phase 2, open-label, multicenter trial evaluating the efficacy and safety of ENHERTU (6.4 mg/kg) in patients with HER2 expressing unresectable and/or metastatic colorectal cancer.
The primary endpoint of the main cohort of DESTINY-CRC01, which enrolled 53 patients with HER2 positive (IHC 3+ or IHC 2+/in-situ hybridization [ISH]+) metastatic colorectal cancer, was confirmed ORR as assessed by independent central review. Secondary endpoints include DCR, DoR, PFS, OS and safety. Two additional exploratory cohorts enrolled patients whose tumors had lower levels of HER2 expression (HER2 IHC 2+/ISH- [n=15], and HER2 IHC 1+ [n=18], respectively).
DESTINY-CRC01 enrolled 86 patients at multiple sites in
About DESTINY-CRC02
DESTINY-CRC02 is a global, randomized, two arm, parallel, multicenter 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 locally advanced, unresectable or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) colorectal cancer of BRAF wild-type, or RAS wild-type and RAS mutant tumor types previously treated with standard therapy. The trial was conducted in two stages. In the first stage, patients (n=80) were randomized 1:1 to receive either 5.4 mg/kg or 6.4 mg/kg of ENHERTU. In the second stage, additional patients (n=42) were enrolled in the 5.4 mg/kg arm.
The primary endpoint is confirmed ORR as assessed by blinded independent central review. Secondary endpoints include DoR, DCR, investigator-assessed confirmed ORR, clinical benefit ratio, PFS, OS and safety.
DESTINY-CRC02 enrolled 122 patients at multiple sites in
About HER2 Expression in Solid Tumors
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.5,7 In some cancers, HER2 expression is amplified or the cells have activating mutations.7,8 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis.9
While HER2 directed therapies have been used to treat breast, gastric, lung and colorectal cancers, more research is needed evaluating their potential role in treating other HER2 expressing tumor types.3,5,10
HER2 is an emerging biomarker in biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers.8 Testing is not routinely performed in these additional tumor types and as a result, available literature is limited. HER2 overexpression has been observed at rates from 1% to 28% in these solid tumors.1,2 There is an unmet need for effective therapies for certain HER2 expressing solid tumors, particularly for those who have progressed on or are refractory to standard of care therapies as there are currently no approved HER2 directed therapies for biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers.5,6
Colorectal cancer is the third most common and second most common cause of cancer deaths worldwide with more than 1.9 million patients diagnosed and more than 935,000 deaths globally in 2020.11 Approximately 25% of patients have metastatic disease at diagnosis, meaning the disease has spread to distant organs and about 50% of patients with colorectal cancer will eventually develop metastases.12 For patients with metastatic disease, up to 5% are HER2 overexpressing.3,4
About ENHERTU
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the
ENHERTU (5.4 mg/kg) is approved in more than 50 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
ENHERTU (5.4 mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
ENHERTU (5.4 mg/kg) is approved in
ENHERTU (6.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 and/or DESTINY-Gastric02 trials.
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. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.
About the
About the DXd ADC Portfolio of
The DXd ADC portfolio of
Designed using
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan and raludotatug deruxtecan are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.
About
Contact:
Email: jbrennan2@dsi.com
Tel: +1 908 900 3183
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