Marketing Applications for Dato-DXd in NSCLC, Breast Cancer Validated in EU

The FDA accepted a biologics license application for dato-DXd for patients with NSCLC in February 2024.

The European Medicines Agency (EMA) has validated 2 marketing authorization applications for datopotamab deruxtecan (dato-DXd) as a treatment for select patients with non–small cell lung cancer (NSCLC) and breast cancer, according to a press release from AstraZeneca, the developer of the agent.¹

Specifically, the NSCLC indication is for adult patients with locally advanced or metastatic nonsquamous disease requiring systemic therapy after prior treatment. Additionally, the other application is for dato-DXd as a treatment for adult patients with unresectable or metastatic hormone receptor (HR)–positive HER2-negative breast cancer that has progressed on prior endocrine therapy and 1 or more additional lines of systemic therapy.

Supporting data for the applications in the NSCLC and breast cancer indications, respectively, came from the phase 3 TROPION-Lung01 trial (NCT04656652) and the phase 3 TROPION-Breast01 trial (NCT05104866).

TROPION-Lung01

Findings from the TROPION-Lung01 trial presented at the 2023 European Society for Medical Oncology (ESMO) Congress highlighted a median progression-free survival (PFS) of 4.4 months (95% CI, 4.2-5.6) with dato-DXd vs 3.7 months (95% CI, 2.9-4.2) with docetaxel; the experimental agent reduced the risk of disease progression or death by 25% (HR, 0.75; 95% CI, 0.62-0.91; P = .004).² Additionally, the median overall survival (OS) was 12.4 months (95% CI, 10.8-14.8) vs 11.0 months (95% CI, 9.8-12.5) in each respective arm (HR, 0.90; 95% CI, 0.72-1.13), and the confirmed objective response rate (ORR) was 26.4% (95% CI, 21.5%-31.8%) vs 12.8% (95% CI, 9.3%-17.1%).

Grade 3 or higher treatment-related adverse effects (TRAEs) affected 25% of patients who received dato-DXd and 41% of those who were treated with docetaxel. The most common high-grade toxicities in each respective arm included neutropenia (1% vs 23%), stomatitis (6% vs 1%), anemia (4% vs 4%), asthenia (3% vs 2%), nausea (2% vs 1%), and fatigue (1% vs 2%).

“For patients with advanced [NSCLC], current standard of care second-line docetaxel is associated with limited benefit and substantial toxicity,” investigator Aaron Lisberg, MD, a thoracic medical oncologist at the University of California, Los Angeles (UCLA), said concerning these findings.² “The improvement in [PFS] observed with datopotamab deruxtecan, particularly in patients with non-squamous tumors, and the improved tolerability of this antibody drug conjugate compared [with] docetaxel, represent a meaningful advance for patients with lung cancer.”

In the international, open-label TROPION-Lung01 trial, patients with locally advanced or metastatic NSCLC were assigned to receive dato-DXd at 6.0 mg/kg or docetaxel at 75 mg/m². The trial’s dual primary end points were PFS and OS. Secondary end points included ORR, duration of response (DOR), time to response, and safety.

TROPION-Breast01

According to findings from the TROPION-Breast01 trial presented at the 2023 San Antonio Breast Cancer Symposium (SABCS), the median PFS by blinded independent central review (BICR) was 6.9 months with dato-DXd and 4.9 months with chemotherapy (HR, 0.63; 95% CI, 0.52-0.76; P <.0001).³ Moreover, the median PFS based on investigator assessment was 6.9 months (95% CI, 5.9-7.1) vs 4.5 months (95% CI, 4.2-5.5) in each respective arm (HR, 0.64; 95% CI, 0.53-0.76).

Any-grade TRAEs occurred in 94% of patients who received dato-DXd and 86% of those who were treated with chemotherapy; grade 3 or higher TRAEs affected 21% and 45%, respectively.

Patients with HR-positive, HER2-low or HER2-negative breast cancer were assigned 1:1 to receive dato-DXd at 6 mg/kg intravenously or investigator’s choice of chemotherapy with eribulin mesylate, vinorelbine, or gemcitabine. The coprimary end points were PFS by BICR and OS. Secondary end points included ORR, time to first subsequent therapy, and safety.

“Our ambition is for datopotamab deruxtecan to improve upon and replace conventional chemotherapy in the treatment of multiple cancer types. Today’s dual validation of our applications in lung and breast cancers brings this potential medicine a meaningful step closer to redefining treatment expectations for patients with 2 of the most common cancers in Europe,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, said in the press release.¹

The FDA accepted a biologics license application for dato-DXd for patients with NSCLC in February 2024.⁴ Supporting data for the application came from the TROPION-Lung01 trial.

References

1. Two datopotamab deruxtecan applications validated in the EU for patients with advanced nonsquamous non-small cell lung cancer or HR-positive, HER2-negative breast cancer. News release. AstraZeneca. March 4, 2024. Accessed March 4, 2024. https://tinyurl.com/3va3hp8n
2. Datopotamab deruxtecan improved progression-free survival vs. chemotherapy in patients with previously treated non-small cell lung cancer in TROPION-Lung01 phase III trial. News release. AstraZeneca. October 23, 2023. Accessed March 4, 2024. https://tinyurl.com/5fpdwm99
3. Bardia A, Jhaveri K, Im SA, et al. Randomized phase 3 study of datopotamab deruxtecan vs chemotherapy for patients with previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer: results from TROPION-Breast01. Presented at: 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Abstract GS02-01
4. Datopotamab deruxtecan biologics license application accepted in the US for patients with previously treated advanced nonsquamous non-small cell lung cancer. News release. AstraZeneca. February 19, 2024. Accessed February 20, 2024. http://tinyurl.com/2v5k3yhc