TROP2-Directed Agent Shows Initial Tolerability In Advanced TNBC Patients

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Datopotamab deruxtecan (Dato-DXd) is tolerated by patients with advanced triple-negative breast cancer (TNBC) and may have antitumour efficacy, indicate phase I trial findings presented at the ESMO Breast Cancer Virtual Congress 2021. 

Aditya Bardia, from Massachusetts General Hospital Cancer Center in Boston, USA, reported the TROPION-PanTumor01 study results for the antibody–drug conjugate directed against tumour-associated calcium signal transducer (TROP)2. 

The first-in-human basket trial advanced TNBC cohort included 24 US and Japanese patients, aged a median 57 years, who had relapsed or progressed on standard treatment and were not prescreened for TROP2 expression. 

The patients had received a median of four prior treatments, with 88% given at least two lines of therapy, most commonly including taxane (83%) and platinum (50%) chemotherapy and immunotherapy (33%), the presenter commented. 

Twenty-two patients were given Dato-DXd 6 mg/kg intravenously every 3 weeks and two patients received a higher 8 mg/kg dose. 

Reporting on the primary objectives of safety and tolerability, the presenter told delegates that Dato-DXd had a “manageable safety profile”, with treatment ongoing at time of data analysis in 75% of the cohort and all discontinuations due to disease progression. 

Grade 3 or more severe treatment-related adverse events (AEs) occurred in 17% of patients, none of which were serious or fatal. A quarter of patients required a dose reduction, mainly for stomatitis (13%) or mucosal inflammation (8%). 

The investigator emphasized that the majority (67%) of treatment-emergent AEs were grade 1 or 2 and nonhaematological, with the most common any-grade AEs being stomatitis (63%), nausea (63%), fatigue (42%), vomiting (42%) and alopecia (25%). 

There were no grade 3 or more severe cases of treatment-emergent diarrhoea or neutropenia, or drug-related interstitial lung disease. 

Of the 21 patients assessed by blinded independent central review, 43% had an objective response, including a confirmed complete or partial response in 24% and a response pending confirmation in 19%. The disease control rate was 95%, with just one patient showing progressive disease. 

“The majority of patients had a decrease in tumour volume”, remarked the investigator, noting this occurred in most patients within 2 months. 

“Emerging efficacy results showed antitumor activity in heavily pretreated patients with metastatic TNBC”, Aditya Bardia concluded.  

He said that further study of Dato-DXd is now warranted in breast cancer patients and a hormone receptor-positive cohort is now being enrolled into the trial. 

Reference  

Bardia A, Juric D, Shimizu T, et al. Datoptamab deruxtecan (Dato-DXd), a TROP2-directed antibody drug conjugate, for triple-negative breast cancer: Preliminary results from an ongoing phase 1 trial. Ann Oncol; 32(suppl_2):S60–S78. DOI: 10.1016/annonc/annonc508