The TROP2-directed antibody-drug conjugate datopotamab deruxtecan (Dato-Dxd) demonstrated promising antitumor efficacy against previously treated non-small cell lung cancer (NSCLC), according to updated results of the phase 1 TROPION-PanTumor01 study presented at the 2020 World Conference on Lung Cancer in Singapore.
NSCLC and other solid tumors express the transmembrane glycoprotein TROP2, and high expression levels are associated with poor outcomes. Dato-Dxd is a TROP2-directed ADC that comprises an anti-TROP2 monoclonal antibody conjugated to a topoisomerase 1 payload. In this phase 1 study (NCT03401385), TROPION-PanTumor01 investigators evaluated Dato-Dxd’s safety and efficacy against relapsed/refractory solid tumors, including NSCLC.
In the NSCLC cohort of the dose-escalation TROPION-PanTumor01 trial, 175 patients with relapsed/refractory NSCLC received Dato-Dxd at 4 mg/kg, 6 mg/kg, or 8 mg/kg. Although a retrospective analysis of TROP2 expression levels is planned, it was not required for study entry.
Patients with stable, treated brain metastases were permitted to participate. The coprimary end points were establishment of the maximum tolerated dose (MTD) and safety and tolerability. The secondary end points included parameters of efficacy and pharmacokinetics.
At baseline, the median patient age was 61 years, 62 years, and 64 years in the 4, 6, and 8 mg/kg dosing groups, respectively. In each group, most patients were male and had nonsquamous histology.
14% of patients had an EGFR mutation, and 37% had a history of brain metastases. Most patients in each group had at least 3 prior lines of therapy. Specifically, 83% had prior immunotherapy; 94%, prior platinum-based chemotherapy; and 17%, a prior tyrosine kinase inhibitor.
The objective response rate ranged from 21% to 25%, and the disease control rate, from 26% to 64% across dose levels. The median progression-free survival was 4.3 months with the 4 mg/kg dose, 8.2 months with the 6 mg/kg dose, and 5.4 months with the 8 mg/kg doses.
Patients in the 8 mg/kg cohort discontinued treatment more frequently, which led to a median lower relative dose intensity compared with patients in the other dose groups.
Discontinuation of study treatment due to adverse events (AEs) occurred among 46%, 51%, and 76% of patients in the 4 mg/kg, 6 mg/kg, and 8 mg/kg arms, respectively. Grade 3 or higher treatment-related AEs also occurred more frequently with the 8 mg/kg dose at 34%, followed by 16% and 10% with the 6 mg/kg and 4 mg/kg doses, respectively. There was 1 treatment-related death in the 4 mg/kg arm and 2 in the 8 mg/kg arm.
The 6 mg/kg dose was selected for the phase 3 TROPION-Lung01 study (NCT04656652), which is currently enrolling 590 patients with previously treated advanced or metastatic NSCLC without actionable genomic alterations.
Dato-Dxd “demonstrated highlight encouraging antitumor activity and a manageable safety profile in heavily pretreated NSCLC patients,” concluded Alexander Spira, MD, who presented the findings.
Disclosures: Alexander Spira, MD, disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
Spira A, Lisberg AE, Sands JM, et al. Datopotamab deruxtecan (Dato-DXd; DS-1062), a TROP2 ADC, in patients with advanced NSCLC: updated results of TROPION-PanTumor01 phase 1 study. Presented at: 2020 World Conference on Lung Cancer Singapore; January 28-31, 2020. Abstract OA03.03.