AstraZeneca Provides Early Insights on Datroway-Tagrisso Combination for EGFR Lung Cancer

AstraZeneca is making significant advances in the treatment of non-small cell lung cancer (NSCLC) with its latest findings regarding the combination therapy of Datroway and Tagrisso. As it awaits a decision from the U.S. Food and Drug Administration (FDA) for its novel antibody-drug conjugate (ADC) Datroway, developed in partnership with Daiichi Sankyo, AstraZeneca has shared promising early data from a phase 2 trial that merges Datroway with its renowned EGFR inhibitor, Tagrisso.

The combination therapy demonstrated an objective response rate (ORR) of **36%** among patients with EGFR-mutant NSCLC who had previously progressed on first-line Tagrisso. These findings originate from module 10 of the phase 2 Orchard trial, which explores various novel combinations in patients post-Tagrisso treatment. The data are set to be presented at the upcoming European Lung Cancer Congress (ELCC) next week.

Trial Insights and Efficacy Measures

The results highlighted the effectiveness of Datroway, administered at a dosage of **6 mg/kg**, yielding a **36%** ORR among a cohort of 33 evaluable patients. Interestingly, a second group of 35 patients who received a lower dosage of **4 mg/kg** recorded an impressive **43%** ORR. Both groups had comparable follow-up periods of around **13 months**, with researchers preferring the higher dosage based on the overall benefit-risk analysis indicated in the abstract.

In October, AstraZeneca in partnership with Daiichi Sankyo initiated the phase 3 Tropion-Lung15 trial, investigating the efficacy of Datroway 6 mg/kg, both as a standalone therapy and in conjunction with Tagrisso for patients with post-Tagrisso EGFR-mutant NSCLC. This trial is estimated to reach primary completion by **June 2026**.

“Cancer resistant to Tagrisso may still exhibit tumor cells containing EGFR mutations,” noted an AstraZeneca spokesperson, providing insight into the rationale for combining Tagrisso with Datroway. “By maintaining Tagrisso, we ensure sustained inhibition of EGFRm-driven cells while administering a targeted therapy to combat the developed mutations.”

Comparative Response Rates and Treatment Timelines

In terms of treatment timelines, the higher dose of Datroway led to a more rapid response, with a median time to onset of **1.4 months** compared to **2.7 months** for the lower dose. Researchers projected that only **15%** of patients on the lower dosage would sustain a response at the nine-month mark, in contrast to **64%** for those on the higher dosage. Furthermore, the duration without disease progression was superior among those receiving the higher dose, averaging **11.7 months**, compared to **9.5 months** for the lower dose.

While the higher dose did correlate with increased adverse events—**56%** of patients experienced grade 3 or higher treatment-related events—no novel safety signals were observed. Adverse events necessitating dose reductions were reported in **59%** of patients receiving the higher dose, versus **23%** in the lower dose cohort. Notably, incidences of interstitial lung disease or pneumonitis emerged in **15%** of patients administered the higher dose—6% being of grade 3 or above.

Future Regulatory Hurdles and Competition

Prior to these groundbreaking results concerning the Datroway-Tagrisso combination, AstraZeneca and Daiichi had sought FDA approval for Datroway as a standalone treatment for previously treated EGFR-mutated NSCLC. A decision from the FDA is anticipated by **July 12, 2025**. This approval is predicated on a pooled analysis from the phase 3 Tropion-Lung01 and phase 2 Tropion-Lung05 trials, revealing an ORR of **43%** among **117** patients who had undergone a median of three previous therapy lines, with responses lasting an average duration of **seven months**.

Apart from their developments, AstraZeneca faces stiff competition in the arena of NSCLC treatments, particularly from Johnson & Johnson’s Rybrevant combined with Lazcluze. The Rybrevant regimen reported a noticeably high **53%** ORR with a **6.9-month** duration of response in post-Tagrisso patients, marking a **52%** reduction in the risk of progression or death when compared to chemotherapy alternatives.

Additional Research Insights

In addition to the Orchard trial data, AstraZeneca disclosed findings from the primary analysis of the phase 2 Savannah trial. This trial, assessing Tagrisso in combination with Hutchmed’s MET inhibitor savolitinib, exhibited a **56%** ORR among a selected patient group demonstrating high MET expression.

Overall, AstraZeneca’s research on the **Datroway-Tagrisso** combination unveils promising potential for patients battling EGFR-mutant NSCLC in the second-line treatment setting, while the competitive landscape is continually evolving. With impending regulatory decisions and emerging data, the future of lung cancer therapies appears to hold considerable promise.