AstraZeneca-Daiichi Sankyo Enhertu gets USFDA accelerated nod for metastatic HER2-positive solid tumours

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The first tumour-agnostic approval of a HER2-directed therapy and ADC by the Food and Drug Administration (FDA) was based on results from the subgroup of patients with HER2-positive IHC 3+ tumours in each of the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 Phase II trials.

Funda Meric-Bernstam, MD, Chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, US, said, “Until the approval of trastuzumab deruxtecan, patients with metastatic HER2-positive solid tumours have had limited treatment options. Based on the clinically meaningful response rates seen across clinical trials, this tumour-agnostic approval means that patients may now be treated with a HER2-directed medicine.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said, “As the first antibody drug conjugate to be granted a tumour-agnostic indication, Enhertu is truly delivering on its potential across metastatic HER2-targetable tumours. This approval also elevates the importance of testing for biomarkers, including HER2, across a broad range of tumours to ensure these patients with advanced cancer who have few options know whether a targeted medicine might be right for them.”

Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc., said, “This fifth indication in the US is a significant milestone as eligible patients with previously treated metastatic HER2-positive solid tumours may now be treated with Enhertu. The accelerated approval by the FDA for this tumour-agnostic indication is based on the clinically meaningful efficacy seen with Enhertu across numerous types of metastatic cancers.”

In the DESTINY-PanTumor02 Phase II trial, patients with centrally or locally assessed HER2-positive (IHC 3+) solid tumours including either biliary tract, bladder, cervical, endometrial, ovarian, pancreatic or other tumours treated with Enhertu showed a confirmed ORR of 51.4% (95% confidence interval [CI] 41.7-61.0) and a median DoR range of 19.4 months (range 1.3-27.9+ [+ denotes ongoing responses at data cutoff]). In DESTINY-Lung01, patients with centrally confirmed HER2-positive (IHC 3+) non-small cell lung cancer (NSCLC) treated with Enhertu showed a confirmed ORR of 52.9% (95% CI 27.8-77.0) and median DoR range of 6.9 months (range 4.0-11.7+). A confirmed ORR of 46.9% (95% CI 34.3-59.8) and median DoR range of 5.5 months (range 1.3+-9.7+) was seen in patients with centrally confirmed HER2-positive (IHC 3+) colorectal cancer in the DESTINY-CRC02 trial.

The safety of Enhertu was evaluated in 347 patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours in the DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. The safety profile observed across the trials was consistent with previous clinical trials of Enhertu with no new safety concerns identified.

Based on these results, fam-trastuzumab deruxtecan-nxki (Enhertu) has been included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a treatment option for multiple metastatic tumours. 

This approval was granted under the FDA’s Real-Time Oncology Review programme after securing Priority Review and Breakthrough Therapy Designation for Enhertu in the US in this setting.

The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Enhertu is also under regulatory review for the same indication by regulatory authorities in Australia, Brazil and Singapore.

Sales of Enhertu in the US are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in the US as alliance revenue in the Company’s financial statements.

Further details on the financial arrangements were set out in the March 2019 announcement of the collaboration.

Read also:AstraZeneca Enhertu granted priority review in US for metastatic HER2-positive solid tumours