Daiichi Sankyo and AstraZeneca announced that Enhertu® (trastuzumab deruxtecan) has been recommended for approval in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+) solid tumors who have received prior treatment and who have no satisfactory treatment options. Enhertu is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from patients with HER2 positive (IHC 3+) tumors in three phase 2 trials including DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 where Enhertu demonstrated clinically meaningful responses across a broad range of tumors.

The recommendation will now be reviewed by the European Commission, which has the authority to grant marketing authorizations for medicines in the EU. In DESTINY-PanTumor02, Enhertu demonstrated a confirmed objective response rate (ORR) of 51.4% (95% confidence interval [CI]: 41.7-61.0) and median duration of response (DOR) of 14.2 months (range: 10.3-23.6) in previously treated patients (n=111) with centrally or locally assessed HER2 positive solid tumors including either biliary tract, bladder, cervical, endometrial, ovarian, pancreatic or other tumors. In DESTINY-Lung01, Enhertu demonstrated a confirmed ORR of 52.9% (95% CI: 27.8-77.0) and median DOR of 6.9 months (range: 4.0-11.7) in previously treated patients (n=17) with centrally confirmed HER2 positive non-small cell lung cancer (NSCLC).

In DESTINY-CRC02, Enhertu demonstrated a confirmed ORR of 46.9% (95% CI: 34.3-59.8) and median DOR of 5.5 months (range: 1.3-9.7) in previously treated patients (n=64) with centrally confirmed HER2 positive colorectal cancer. The safety profile of Enhertu (5.4 mg/kg) across the trials was consistent with previous clinical trials with no new safety concerns identified. In DESTINY-PanTumor02, the most common grade 3 or higher drug-related adverse events that occurred in all patients treated with Enhertu (n=267) were neutropenia (10.9%) and anemia (10.9%).

Interstitial lung disease (ILD) or pneumonitis occurred in 10.5% of patients. The majority of ILD or pneumonitis events were low grade (grade 1 or 2), with one grade 3 event (0.4%), no grade 4 events (0.0%) and three grade 5 events (1.1%) observed, as determined by an independent adjudication committee. In DESTINY-Lung01, the most common grade 3 or higher treatment-emergent adverse events (TEAEs) occurring in all patients treated with Enhertu (cohort 1a; n=41) were disease progression (10%), fatigue (7%), pneumonia (5%) and dyspnea (4%).

ILD or pneumonitis occurred in 5% of patients. The majority of ILD or pneumonitis events were low grade (grade 1 or 2), with no grade 3 or grade 4 events (0.0%), and one grade 5 event (2%) observed, as determined by an independent adjudication committee. One additional patient experienced grade 4 pneumonitis after the data cutoff, which was subsequently adjudicated as a drug-related grade 5 event.

In DESTINY-CRC02, the most common grade 3 or worse TEAEs occurring in all patients treated with Enhertu (n=83) were decreased neutrophil count (16%), anemia (7%), nausea (7%) and decreased white blood cell count (6%). ILD or pneumonitis occurred in 8% of patients. All ILD or pneumonitis events were low grade (grade 1 or 2) with no grade 3, grade 4 or grade 5 events (0.0%) observed, as determined by an independent adjudication committee.