Dato-DXd (datopotamab deruxtecan) combined with Imfinzi (durvalumab) with or without carboplatin led to improvements in outcomes with no new safety signals for patients with previously untreated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations, according to the TROPION-Lung04 phase 1b trial.
Imfinzi, an anti-PD-L1 therapy and immune checkpoint inhibitor drug, and Dato-DXd, an antibody drug conjugate created by AstraZeneca and Daiichi Sankyo, both treat patients with NSCLC. Three trials are set to evaluate the use of Dato-DXd and other checkpoint inhibitors in treating first line advanced NSCLC.
“These early trial results further demonstrate the potential for Dato-DXd to enhance response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer and without actionable genomic alterations. We look forward to continuing to evaluate this promising TROP2-directed antibody drug conjugate in multiple ongoing phase 3 trials to address what has long been an unmet need for the lung cancer community across treatment settings,” Dr. Mark Rutstein,Global Head of Oncology Clinical Development at Daiichi Sankyo, explained in a press release.
Data from the TROPION-Lung04 phase 1b trial was presented at the International Association for the Study of Lung Cancer (IASLC) 2023 World Conference on Lung Cancer (WCLC). This trial is continuing to focus on the efficiency and safety of Dato-DXd and Imfinzi with or without four cycles of carboplatin for patients with NSCLC without actionable genomic alterations. An estimated 230 patients are estimated to enroll in the continuous trial globally.
Dato-DXd combined with Imfinzi showed an objective response rate (ORR; percentage of patients whose disease shrunk or disappeared from treatment) of 50% and a disease control rate (DCR) of 92.9%. When adding carboplatin to Dato-DXd combined with Imfinzi, the response rates increased, with an ORR of 76.9% and a DCR of 92.3%.
“Following the positive high-level results of TROPION-Lung01, these initial TROPION-Lung04 results in the first-line setting reinforce our confidence in (Dato-DXd) as a potential treatment option for patients with advanced non-small cell lung cancer. Through our robust clinical program we are eager to continue evaluating this TROP2-directed antibody drug conjugate in lung cancer across treatment settings, alone and in novel combinations,” explained Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer at AstraZeneca.
The safety profiles after evaluating Dato-DXd and Imfinzi remained the same compared to other clinical trials. Grade 3 or higher treatment-related side effects were observed in 42.1% of patients who underwent doublet therapy, and 71.4% of patients who undergoing triplet therapy. Anemia (36%) and thrombocytopenia (21%) were the most common side effects in patients who are undergoing triplet therapy. When it came to doublet therapy, no grade 3 side effects occurred in more than 15% of patients, according to AstraZeneca.
A total of 73.7% of patients were previously untreated within the doublet cohort, alongside 92.9% in the triplet cohort. Both cohorts had patients with PD-L1 expressions, ranging from less than 1% to greater than 50%. The median study duration for both cohorts since March 2023 was six months, with an ongoing treatment of 31.6% and 50%, according to AstraZeneca.
NSCLC effects more than one million people each year. Although first line treatment has improved outcomes with the help of immune checkpoint inhibitors with or without chemotherapy, disease progression is still evident within patients.
“Most patients with advanced non-small cell lung cancer experience disease progression after initial treatment, underscoring the need for more effective first-line treatment options. The TROPION-Lung04 results offer preliminary evidence for the efficacy of (Dato-DXd) in combination with (Imfinzi) and chemotherapy in first-line advanced non-small cell lung cancer with no new safety signals. We eagerly await enrolment and results from the phase 3 program evaluating various (Dato-DXd) and immune checkpoint inhibitor combinations in this setting,” Dr. Saiama Waqar, of the Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, and investigator in the trial, said in the release.
AstraZeneca and Daiichi Sankyo are evaluating Dato-DXd combinations in three other clinical trials for patients with advanced or metastatic NSCLC without actionable genomic alterations in comparison with standard care for the patient population, according to AstraZeneca.
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