Datopotamab Deruxtecan Shows Promise in Advanced/Metastatic HER2- Breast Cancer

The antibody-drug combination known as datopotamab deruxtecan (Dato-DXd) is composed of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a powerful topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. Dato-DXd shows promising antitumor activity and a manageable safety profile in patients with NSCLC (Meric-Bernstam, ASCO 2021) and TNBC (Bardia, ESMO BC 2021), according to preliminary results from the phase 1 TROPION-PanTumor01 study. Phase 1, multicenter, open-label, 2-part study of Dato-DXd in previously treated patients with solid tumors; NCT03401385. Dato-DXd 6 mg/kg intravenously every 3 weeks is being tested in patients with advanced/metastatic TNBC and HR+/HER2 breast cancer who have relapsed/progressed on conventional therapy, based on dose-escalation outcomes in patients with NSCLC. Dato-DXd 8 mg/kg was given to two TNBC patients before a 6 mg/kg dose was chosen for expansion. Objective response rate (ORR) was measured using RECIST version 1.1 as an efficacy endpoint, and both safety and efficacy were evaluated using a blinded independent central review (BICR). By the data cutoff date of April 6, 2021, 43 patients with TNBC had received at least one dosage of Dato-DXd, with 27 patients continuing treatment (63%) and 16 patients quitting due to disease progression (37%). The average age was 53 (the age range was 32-82).

Among these 41 patients, 19 (44%) had previously been treated with immunotherapy, and 7 (16%) had previously been treated with sacituzumab govitecan. It took patients an average of 2.8 months (0.7-9.0) to complete their treatment. Duration of follow-up varied from 0.3 to 9.2 months (median = 3.9 months). There were 38 patients whose responses could be assessed, and the ORR by BICR was 39% (15 PR; 12 confirmed, 3 pending), 84% of cases (32 out of 38) were successfully treated. The 12 confirmed PRs had a median response time of 1.35 months (1.2-3.2 months). Ninety-five percent of patients experienced treatment-emergent adverse events (TEAEs; any grade, grade 3), while 35% experienced TEAEs of any grade. Nausea (58%) and stomatitis (53%), alopecia (35%), vomiting (35%), and fatigue (33%) were the most frequently reported TEAEs (any grade [30%], grade 3). There was just one instance of diarrhea of grade 3 and one case of reduced neutrophil count. According to the findings of a third-party commission, there were no incidences of interstitial lung disease caused by the treatment. Five individuals (12%) experienced serious TEAEs, although no TEAEs were fatal. Nine patients’ dosage decreased due to side effects like stomatitis, tiredness, mucosal inflammation, dry eye, retinal exudates, and blurred vision (multiple counts per TEAE). As a result of stomatitis, mucosal inflammation, bronchitis, and muscular chest pain, three patients had to stop taking their medication temporarily. There were no treatment-related withdrawals from any patients. Confirmatory studies in patients with breast cancer are necessary since preliminary data showed that Dato-DXd displays potential anticancer effectiveness with a tolerable safety profile in patients with previously treated advanced/metastatic TNBC.

Source:http://app.core-apps.com/sabcs2021/abstract/93dbbc3d-205a-4aa7-8354-96ef20ee519a

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03401385

Ian Krop, Dejan Juric, Toshio Shimizu, Anthony Tolcher, Alexander Spira, Toru Mukohara, Aaron E. Lisberg, Takahiro Kogawa, Kyriakos P. Papadopoulos, Erika Hamilton, Senthil Damodaran, Jonathan Greenberg, Wen Gu, Fumiaki Kobayashi, Ferdinand Guevara, Takahiro Jikoh, Yui Kawasaki, Funda Meric-Bernstam, Aditya Bardia/Datopotamab deruxtecan in advanced/metastatic HER2- breast cancer: Results from the phase 1 TROPION-PanTumor01 study/2021 San Antonio Breast Cancer Symposium. (n.d.). App.core-Apps.com. Retrieved May 1, 2023, from http://app.core-apps.com/sabcs2021/abstract/93dbbc3d-205a-4aa7-8354-96ef20ee519a

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