Enhertu Receives FDA Accelerated Approval for Unresectable or Metastatic HER2-Positive Solid Tumors

April 6,AstraZenecaAndDaiichi-SankyoJointly AnnouncedEnhertu（Trastuzumab Deruxtecan) has been granted accelerated approval by the U.S. FDA for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic therapy and have no satisfactory alternative treatment options.

Trastuzumab deruxtecan is an antibody-drug conjugate (ADC) targeting HER2, designed using Daiichi Sankyo's proprietary DXd ADC technology. It consists of a HER2 monoclonal antibody linked via a stable tetrapeptide cleavable linker to a topoisomerase I inhibitor payload (a derivative of exatecan).Up.This product is jointly developed and promoted globally by Daiichi Sankyo and AstraZeneca, while Daiichi Sankyo holds exclusive commercialization rights for this product in Japan.

The FDA granted accelerated approval for this indication based on the objective response rate (ORR) and duration of response (DoR) in HER2-positive IHC 3+ subgroup tumor patients from the DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02 trials. Full approval will depend on the verification and description of clinical benefit in confirmatory trials.

DESTINY-PanTumor02 is a global, multi-A central, open-label, multi-cohort Phase II clinical trial aimed to evaluate the efficacy and safety of Enhertu (5.4mg/kg) in patients with locally advanced, unresectable, or metastatic HER2-expressing solid tumors who have received prior treatment, including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, or other tumors.

The primary endpoint of the study was the objective response rate (ORR) confirmed by the investigator, and the secondary endpoints includedAlleviateDuration of Response (DoR), Disease Control Rate (DCR), Progression-Free Survival (PFS), Overall Survival (OS), safety, tolerability, and pharmacokinetics. A total of 267 patients were enrolled across multiple research centers in Asia, Europe, and North America.

As of June 8, 2023, the median follow-up time was 12.75 months.The results showed that the confirmed ORR assessed by investigators in the overall study population of patients (n=267) with HER2-expressing advanced solid tumors previously treated was 37.1% (95% [CI]:31.3-43.2），The median DoR was 11.3 months (95% CI:9.6-17.8), with a median PFS of 6.9 months (95% CI:5.6-8.0), with a median OS of 13.4 months (95% CI:11.9-15.5)。

The results of the exploratory analysis showed,Patients with centrally confirmed HER2 expression in tumors, or immunohistochemistry (IHC) 3+ (n=75), demonstrated the highest response rate, with a confirmed ORR of 61.3% (95% CI: 49.4-72.4), median DoR of 22.1 months (95% CI: 9.6-NR), median PFS of 11.9 months (95% CI: 8.2-13.0), and median OS of 21.1 months (95% CI: 15.3-29.6).