AstraZeneca and Daiichi Sankyo have delivered more evidence that their TROP2-directed antibody-drug conjugate (ADC) may have a future in non-small cell lung cancer (NSCLC), linking the candidate to a roughly 40% overall response rate when used as part of doublet and triplet combination therapies.
The partners kicked off the Tropion-Lung02 NSCLC trial after linking their ADC datopotamab deruxtecan, also called Dato-DXd, to a 21% overall response rate in an earlier study, offering encouragement that it can provide a new treatment option for patients who progress after receiving immunotherapy plus platinum-based chemotherapy. To further explore that idea, and assess first-line use, Tropion-Lung02 added the ADC to Merck’s Keytruda, with and without platinum chemotherapy, in patients without actionable genomic alterations.
In the 38 patients who received the Dato-DXd-Keytruda doublet therapy, AstraZeneca and Daiichi saw an ORR of 37%. The response rate was higher, 62%, in patients who received the combination as a first-line therapy. There were no complete responses. Keytruda achieved a 45% ORR in a separate first-line single agent trial. When used in second and later lines of therapy, the doublet combination had an ORR of 24%.
Similar results were seen in the cohort of 37 patients who received the triplet combination that added platinum chemotherapy to the mix. In that cohort, the overall response rate clocked in at 41%, reflecting a 50% rate in the first-line setting and 29% rate when used in the second line and beyond. Some of the partial responses that contributed to the 50% first-line response rate are still pending confirmation.
On the safety front, 40% and 60% of patients in the doublet and triplet cohorts, respectively, experienced grade 3 or greater treatment-emergent adverse events. There were four interstitial lung disease events determined to be drug-related, including two grade 3 events. None of the lung events were grade 4 or 5.
The data drop, which AstraZeneca presented in a late-breaking mini-oral presentation at the International Association For The Study Of Lung Cancer’s 2022 Conference, comes months after the partners began a phase 3 clinical trial of the Dato-DXd-Keytruda doublet therapy in NSCLC patients. The 740 participants in Tropion-Lung08 will take either the doublet therapy or single agent Keytruda as a first-line therapy.
“These data support the initiation of the Tropion-Lung08 phase 3 trial to further evaluate datopotamab deruxtecan in combination with pembrolizumab as a first-line combination treatment in patients with advanced non-small cell lung cancer without actionable genomic alterations,” Gilles Gallant, Ph.D., global head, oncology development, oncology R&D at Daiichi, said in a statement.