According to results from a global, dose-escalation and dose-expansion study presented at the 2023 ASCO Annual Meeting, datopotamab deruxtecan plus pembrolizumab with or without the addition of cisplatin or carboplatin demonstrated tolerable safety and notable first-line activity in patients with advanced non-small cell lung cancer (NSCLC).

These findings were presented by lead author Yasushi Goto, MD, National Cancer Center Hospital, Tokyo, Japan, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting on Tuesday, June 6, 2023 in Chicago, Illinois.

In the TROPION-Lung02 study, patients were received either 4 mg/kg or 6 mg/kg of datopotamab deruxtecan, plus 200 mg of pembrolizumab, with or without either cisplatin or carboplatin every 21 days. Patients in the dose escalation phase were eligible if they had received ≤2 prior lines of therapy for advanced NSCLC. Patient in the dose expansion phase were primarily treatment-naïve, but patients in the combination datopotamab deruxtecan plus pembrolizumab cohorts may have received ≤1 prior lines of platinum-based therapy. Primary objectives in this study included safety, tolerability, and dose-limiting toxicities.

At the data cutoff date of October 31, 2022, a total of 120 patients had been treated with a median treatment duration of 4.6 months, with 66 patients (55%) receiving treatment at the time of data cutoff. All cohorts met the dose-limited toxicity criteria and were eligible to move onto the escalation cohort.

In both the dose escalation and expansion subsets, there was a disease control rate of 85% and median duration of response was not reached. Patients on any line of therapy and doublet therapy displayed The objective response rate (ORR) for any line of therapy on the doublet treatment was 38%, and on triplet therapy was 47%. The ORR for first-line datopotamab deruxtecan plus pembrolizumab was 60% and 55% for datopotamab deruxtecan plus pembrolizumab .

The most frequent treatment-related adverse events included nausea (45%) and stomatitis (45%). There were 61% of patients who experienced grade ≥3 treatment-related adverse events, including a decrease in neutrophil count (8%), and an increase in amylase (8%). Dose reductions in datopotamab deruxtecan due to adverse events occurred in 17% of patients. Interstitial lung disease occurred in 12 patients (10%; grade 1/2, n=9; grade 3, n=3).

Serious treatment-related adverse events occurred in 31% of patients, while events associated with discontinuation or death occurred in 24% and 6% of patients, respectively. Of the serious events, 16% were associated with datopotamab deruxtecan.

Dr Goto and coauthors concluded datopotamab deruxtecan plus pembrolizumab with or without platinum chemotherapy “demonstrated tolerable safety with notable [first-line] activity in this first and largest dataset” evaluating an antibody drug conjugate, plus immunotherapy, plus without or without platinum chemotherapy for patients with advanced NSCLC.

Source

Goto Y, Su WC, Levy BP, et al. TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) in advanced non-small cell lung cancer (aNSCLC). Presented at 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract 9004