AstraZeneca, Daiichi Sankyo Submit Biologics License Application of Datopotamab Deruxtecan for Advanced Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer

Image Credit: Adobe Stock Images/Media Srock

AstraZeneca and Daiichi Sankyo have submitted a Biologics License Application (BLA) to the FDA for accelerated approval of datopotamab deruxtecan (Dato-DXd), targeting adults with previously treated, advanced epidermal growth factor receptor-mutated (EGRF) mutated non-small cell lung cancer (NSCLC). According to AstraZeneca, the decision also means that the companies have withdrawn a previous BLA for Dato-DXd in patients with advanced or metastatic nonsquamous NSCLC based on the TROPION-Lung01 Phase III trial, as per information by the FDA.¹

“TROPION-Lung01 was designed to test the potential to improve upon standard-of-care chemotherapy in a broad, previously treated, advanced lung cancer patient population. The results, together with data from TROPION-Lung05, showed an especially pronounced benefit for patients with an EGFR mutation which informed our discussions with the FDA and the decision to seek accelerated approval of datopotamab deruxtecan in this patient population. TROPION-Lung01 has also provided exciting exploratory data supporting our biomarker development, which will be validated in ongoing and planned Phase III lung cancer trials,” said Susan Galbraith, EVP, oncology R&D, AstraZeneca, in a press release.

The new BLA is based on results from the TROPION-Lung05 Phase II trial, which is a global, multicenter, single-arm, open-label trial evaluating the efficacy and safety of datopotamab deruxtecan in patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have progressed on or after one regimen of platinum-based chemotherapy and at least one TKI. The primary endpoint of the trial was objective response rate (ORR) as assessed by blinded independent central review (BICR), with secondary endpoints including duration of response (DoR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), time to response (TTR), overall survival (OS) and safety. The BLA was also supported by the TROPION-Lung01 study.

Currently, AstraZeneca and Daiichi Sankyo are in the process of evaluating Dato-DXd in combination with Tagrisso (osimertinib) in patients with advanced or metastatic EGFR-mutated nonsquamous NSCLC in the ongoing TROPION-Lung14 and TROPION-Lung15 Phase III trials. An additional trial in trial in patients with biomarker-positive tumors in the 2nd-line nonsquamous NSCLC setting is in the planning stages.¹

According to a 2016 study published in The National Institutes of Health, a total of 456 previous studies were estimated, determining that approximately 32.3% of all patients with NSCLC had EGRF mutations.²

According to the American Cancer Society, anywhere from 80% to 85% of all lung cancers are NSCLC, making it the most common form. By the end of the year, it is estimated that there will be 234,580 new cases of lung cancer in the United States, with 125,070 deaths expected to be reported. Currently, it is the leading cause of cancer-related deaths in the United States, accounting for one in every five deaths. Annually, more people die as a result of it than a combination of colon, breast, and prostate cancers. While it mainly develops in people over 65 years of age, there are small number of cases reported in patients under 45 years of age. Despite this, the number of new lung cancer cases continues to decrease, partly because more people are either quitting smoking or not starting.³

“Treating EGFR-mutated non-small cell lung cancer is incredibly challenging following disease progression given that the complexity and variability of these mutations often lead to resistance. The potential approval of datopotamab deruxtecan could offer renewed hope for patients with this formidable disease,” said Ken Takeshita, MD, global head, R&D, Daiichi Sankyo, in the press release.

References

1. Datopotamab deruxtecan new BLA submitted for accelerated approval in the US for patients with previously treated advanced EGFR-mutated non-small cell lung cancer. AstraZeneca. November 12, 2024. Accessed November 12, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/dato-dxd-new-bla-submitted-nsq-bla-withdrawn.html

2. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. Accessed November 12, 2024. https://www.oncotarget.com/article/12587/text/

3. Key Statistics for Lung Cancer. American Cancer Society. Accessed November 12, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html