AstraZeneca and Eisai's HER2-Targeted ADC Enhertu Shows 57.5% ORR in HER2 IHC3+ Metastatic Colorectal Cancer Patients in DESTINY-CRC01 Trial
Jan 23, 2022 03:35
CST Updated
03:35
AstraZeneca
Biopharmaceutical Manufacturer
Eisai
Pharmaceutical Product R&D and Manufacturer
Colorectal Cancer (Image Source: medicalnewstoday.com)
News on January 22, 2022 /BioValleyBIOON/ -- Recently,AstraZeneca(AstraZeneca) and its partner Eisai Co., Ltd. at the 2022 American Society of Clinical Oncology GastrointestinalTumorThe final results of the DESTINY-CRC01 Phase 2 study (NCT03384940), a multicenter, open-label trial investigating Enhertu (trastuzumab deruxtecan) for HER2-positive unresectable and/or metastatic colorectal cancer (CRC), were presented at the ASCO GI Symposium.
Data show that Enhertu demonstrated clinically meaningful anti-TumorActivity, overall safety and tolerability consistent with previously reported EnhertuClinical TrialConsistent.Currently, there are no drugs specifically approved for the treatment of HER2-positive CRC.
Enhertu is a next-generation antibody-drug conjugate (ADC) that links trastuzumab (a humanized monoclonal antibody targeting HER2) with a novel topoisomerase I inhibitor, an exatecan derivative (DX-8951 derivative, DXd), via a tetrapeptide linker. It can deliver cytotoxic agents directly into cancer cells, reducing systemic exposure to cytotoxic agents compared to conventional chemotherapy.
To date, Enhertu (5.4mg/kg) has been approved in multiple countries as a monotherapy for the treatment of unresectable or metastatic HER2-positive breast cancer in patients who have received two or more prior anti-HER2 based regimens in the metastatic setting.Breast CancerAdult patients. Additionally, Enhertu (6.4mg/kg) has also been approved in multiple countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have previously received a trastuzumab-based regimen.
DESTINY-CRC01 Study in HER2-Positive, RAS Wild-Type mCRC Patients Who Had Progressed on ≥2 Prior Lines of Therapy. The study includes three cohorts (A: HER2 IHC3+ or IHC2+/ISH+; B: IHC2+/ISH−; C: IHC1+), with Enhertu administered at a dose of 6.4 mg/kg every three weeks (Q3W). The primary endpoint is the objective response rate (ORR) assessed by independent central review in Cohort A. Secondary endpoints include disease control rate (DCR=complete response [CR] + partial response [PR] + stable disease [SD]), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
Results: As of the data cutoff date (December 28, 2020), 86 patients (Cohort A=53; Cohort B=15; Cohort C=18) had received Enhertu treatment. The median age was 58.5 years (range: 27-79 years), 53.5% were male, and 90.7% had left-sided colon or rectal cancer. The median number of prior treatment regimens for metastatic disease was 4 (range: 2-11). All patients had received irinotecan; 30.2% in Cohort A had previously received anti-HER2 therapy. The median treatment duration (all patients) was 3.0 months (95% CI: 2.1-4.1; Cohort A, 5.1 months [95% CI: 3.9-7.6]).
In Cohort A (median follow-up: 62.4 weeks), the confirmed ORR was 45.3% (n=24/53; 95% CI: 31.6-59.6), and the DCR was 83.0% (n=44/53; 95% CI: 70.2-91.9).The median DOR was 7.0 months (95% CI: 5.8-9.5), the median PFS was 6.9 months (95% CI: 4.1-8.7), with 37 PFS events (69.8%), and the median OS was 15.5 months (95% CI: 8-20.8), with 36 OS events (67.9%). These results were consistent with the preliminary analysis.
In Cohort A, forThe confirmed ORR was 43.8% in patients previously treated with anti-HER2 therapy.(95%CI:19.8-70.1); forPatients with IHC3+ status had a confirmed ORR of 57.5%.(95% CI: 40.9-73.0); for patients with IHC2+/ISH+ status, the confirmed ORR was 7% (95% CI: 0.2-36.0).
In cohort B and cohort C, the median PFS was 2.1 months (95% CI: 1.4-4.1) and 1.4 months (95% CI: 1.3-2.1), respectively, and the median OS was 7.3 months (95% CI: 3.0-NE) and 7.7 months (95% CI: 2.2-13.9), respectively.
≥Grade 3 treatment-emergent adverse events (TEAEs) occurred in 65.1% of patients, with the most common TEAEs being hematological and gastrointestinal. TEAEs leading to discontinuation occurred in 13 patients. Interstitial lung disease (ILD) related to Enhertu was observed in 8 patients (4 with Grade 2; 1 with Grade 3; 3 with Grade 5).
Conclusion: Long-term follow-up shows that the 6.4 mg/kg Q3W regimen of Enhertu demonstrates favorable activity in HER2-positive metastatic colorectal cancer (mCRC) patients. Safety is consistent with previous results; ILD remains an important identified risk, requiring careful monitoring and intervention as needed. (Bioon.com)