AstraZeneca (AZ) and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) continued to demonstrate clinically meaningful tumour responses in previously treated patients with HER2-mutant (HER2m) unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC) in an ongoing phase 2 trial, the companies announced.
Enhertu (5.4mg/kg) was approved by the US Food and Drug Administration (FDA) in August for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have activating HER2 mutations, and who have received a prior systemic therapy.
Lung cancer is the leading cause of cancer-related deaths worldwide. NSCLC is diagnosed at an advanced stage in nearly 50% of patients and often has a poor prognosis with worsening outcomes after each line of subsequent therapy.
There are treatment options available for those diagnosed with stage 3 NSCLC, however if a patient progresses to stage 4 – otherwise known as metastatic cancer – the options available are often limited to the prolonging of life and palliative care provisions.
At a pre-specified interim analysis of the DESTINY-Lung02 phase 2 trial, patients receiving Enhertu – a specifically engineered HER2-directed antibody drug conjugate (ADC) – at a dose of 5.4mg/kg or 6.4mg/kg demonstrated clinically meaningful activity, the companies reported.
The safety profile for both doses was also consistent with the overall safety profile of Enhertu, with the 5.4mg/kg dose demonstrating a ‘favourable safety profile’ in this patient population.
A confirmed objective response rate (ORR) of 53.8% was seen in the 5.4mg/kg and 6.4mg/kg arms respectively, and one complete response (CR) was observed in each arm, with 51.9% partial responses (PR) observed in the 5.4mg/kg arm and 39.3% PRs observed in the 6.4mg/kg arm.
A median duration of response (DoR) was not reached in the 5.4mg/kg arm. Consequently, an additional 90-day follow-up response analysis was conducted, where Enhertu demonstrated a confirmed ORR of 57.7% and a median DoR of 8.7 months, with CRs seen in 1.9% of patients and PRs in 55.8% of patients.
Commenting on the positive results, Ken Takeshita, global head of R&D, Daiichi Sankyo, said: “The DESTINY-Lung02 results are consistent with the data previously seen with Enhertu in non-small cell lung cancer and the efficacy demonstrated in this interim analysis, which supported the recent US FDA accelerated approval of Enhertu in patients with HER2-mutant non-small cell lung cancer, reinforces the potential to establish this medicine as a treatment option for these patients.”