Among patients with advanced or metastatic non-small cell lung cancer (NSCLC) with actionable genomic alterations, encouraging and durable antitumor activity was observed during treatment with Datroway (datopotamab deruxtecan), according to study findings published in the Journal of Clinical Oncology.
Furthermore, the rate of grade 3 (severe) or worse treatment-related side effects was similar with previous observations, with no new observed safety signals.
“[Datroway] elicited promising [objective response rates], durable responses, and an acceptable safety profile in heavily pretreated patients with advanced NSCLC and actionable genomic alterations, including in the two predominant EGFR [epidermal growth factor receptor]-mutation and ALK [anaplastic lymphoma kinase]-rearrangement subgroups,” study authors wrote. “These findings suggest that this novel TROP2-directed [antibody-drug conjugate] may provide clinically meaningful benefit in a difficult-to-treat population with poor prognosis and lack of effective therapies.”
Specifically, after a median treatment duration was 4.4 months, the confirmed overall response rate was 35.8%, including 43.6% in patients with EGFR mutations and 23.5% in those with ALK rearrangements. The median duration of response was seven months, and the overall disease control rate was 78.8%.
Glossary:
Progression-free survival: time from treatment start to disease progression or death.
Duration of response: time from response onset to disease progression or death.
Monoclonal antibody: lab-made protein targeting specific antigens.
Trophoblast cell-surface antigen-2: protein linked to tumor growth and spread.
Topoisomerase 1 inhibitor payload: drug blocking DNA replication to kill cancer cells.
Stomatitis: inflammation of the mouth and lips.
Interstitial lung disease: lung disorders causing scarring and breathing issues.
Pneumonitis: lung inflammation from infection, radiation or drugs.
Regarding safety, grade 3 or worse treatment-related side effects occurred in 28.5% of patients. The most common side effect was stomatitis, occurring in 56.2% of patients at any grade and in 9.5% at grade 3 or higher. Adjudicated treatment-related interstitial lung disease or pneumonitis occurred in five patients (3.6%), including one grade 5 (fatal) event (0.7%).
Overall, 129 patients (94.2%) had any-grade severity of treatment-related side effects, and 39 (28.5%) had grade 3 or higher. Treatment-related side effects also led to dose reductions in 27 patients (19.7%), dose delays in 29 (21.2%) and discontinuations in seven (5.1%).
“The safety profile of [Datroway] was manageable, characterized by a low incidence of hematologic or treatment-related grade 3 [or worse] toxicities, consistent with the earlier phase 1 clinical experience,” study authors wrote.
According to the study, Datroway is a trophoblast cell-surface antigen-2–directed antibody-drug conjugate with a highly potent topoisomerase 1 inhibitor payload.
An antibody-drug conjugate is a monoclonal antibody chemically linked to a drug, as per the National Cancer Institute’s website. The antibody binds to specific proteins or receptors on certain cells, including cancer cells, allowing the drug to enter and kill them without harming other cells.
A total of 137 patients received at least one dose of Datroway, of which, 56.9% had EGFR mutations, and 24.8% had ALK rearrangements. In addition, 71.5% of patients received at least three lines of prior therapies for advanced or metastatic disease. Patients received 6 milligrams per kilogram of Datroway, through the vein, once every three weeks on day 1 on each 21-day cycle.
Reference:
“Datopotamab Deruxtecan in Advanced or Metastatic Non–Small Cell Lung Cancer With Actionable Genomic Alterations: Results From the Phase II TROPION-Lung05 Study,” by Dr. Jacob Sands, et al., Journal of Clinical Oncology.
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