AstraZeneca, Daiichi Sankyo’s Dato-DXd With Merck’s Keytruda Shows Positive Data for NSCLC

Datopotamab deruxtecan (Dato-DXd; AstraZeneca, Daiichi Sankyo) in combination with pembrolizumab (Keytruda; Merck) with or without platinum chemotherapy showed promising clinical activity and a tolerable safety profile in individuals with previously untreated or pretreated, advanced or metastatic non­­–small cell lung cancer (NSCLC) without actionable genomic alterations.

Datopotamab deruxtecan is a specifically designed TROP2-directed DXd antibody drug conjugate.

“Many patients with advanced [NSCLC] still experience disease progression following initial treatment, underscoring the need for new therapeutic approaches. The initial results from the TROPION-Lung02 trial show encouraging efficacy and safety results when combining datopotamab deruxtecan and pembrolizumab with or without platinum chemotherapy and warrant further study in the first-line metastatic setting,” Benjamin Philip Levy, MD, clinical director of medical oncology at Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, said in a statement.

The interim analysis of the ongoing TROPION-Lung02 trial showed an overall response rate (ORR) of 37% in individuals who were treated with datopotamab deruxtecan and pembrolizumab (doublet therapy) and an ORR of 41% of those treated with the combination therapy and platinum chemotherapy (triplet therapy).

Investigators saw a disease control rate (DCR) of 84% with both the doublet and triplet therapies in the overall population comprising both the first- and second-line settings.

In patients who were previously untreated, investigators observed an ORR of 62% receiving the doublet therapy and 50% for those receiving the triplet therapy. Additionally, there were 8 partial responses (PRs) in individuals receiving the doublet therapy and 10 PRs for those on the triple therapy.

A DCR of 100% was observed in the doublet therapy, and a DCR of 90% was seen with the triplet.

The combinations with the drug demonstrated a tolerable safety profile, with a grade 3 or greater treatment-emergent adverse event (TEAE) occurring in 40% and 60% of individuals in the doublet and triplet cohorts, respectively.

The most common TEAEs of any grade in either cohort were anemia, decreased appetite, fatigue, nausea, and stomatitis.

Additionally, there were 4 interstitial lung disease events determined as drug-related by an independent adjudication committee across both cohorts.

“These early findings from TROPION-Lung02 are promising and represent the first lung cancer trial to report results combining a TROP2-directed ADC with an immune checkpoint inhibitor with or without platinum chemotherapy in patients with advanced or metastatic [NSCLC],” Gilles Gallant, senior vice president and global head of Oncology Development and Oncology R&D at Daiichi Sankyo, said in the statement. “These data support the initiation of the TROPION-Lung08 Phase III trial to further evaluate datopotamab deruxtecan in combination with pembrolizumab as a 1st-line combination treatment in patients with advanced non-small cell lung cancer without actionable genomic alterations.”

The results from the TROPION-Lung02 phase 1b trial were presented during a late-breaking presentation at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer.

Reference

Late-breaking oral presentation at WCLC features first results from TROPION-Lung02 trial of AstraZeneca and Daiichi Sankyo’s TROP2-directed antibody drug conjugate. News release. AstraZeneca. August 9, 2022. Accessed August 9, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/datopotamab-deruxtecan-based-combinations-show-promising-clinical-activity-in-patients.html