TROP2 ADC Shows Promise in Pretreated TNBC: Erika Hamilton, MD

DB-1305/BNT325, a TROP2-targeted antibody-drug conjugate (ADC), showed encouraging efficiency in treating patients with heavily pretreated metastatic triple-negative breast cancer (TNBC) in a recent clinical trial. The abstract findings were presented at the European Society of Oncology Medicine earlier this year.¹

The findings were presented by lead author Erika Hamilton, MD, a breast cancer researcher and oncologist at the Sarah Cannon Institute. All 26 patients in this phase 1/2 clinical trial (NCT05438329) received at least 2 prior lines of therapy, whether that be immunotherapy, platinum-based chemotherapy, or bevacizumab. Given that this clinical trial assessed 3rd-line therapies and beyond, it’s difficult to compare to previous clinical trials for TNBC, which assessed 1st-line therapies, like the ASCENT-03 and TROPION-Breast02 trials, Hamilton said in an interview with The American Journal of Managed Care^®.

“[However], the response rate of about 34% actually compares quite favorably, for example, with single-agent chemotherapy and 3rd-line triple-negative breast cancer,” she said, referencing the early phase 1/2 ASCENT trial, with an objective response rate of 33.3% in patients with TNBC.² “In addition to that, we had a disease control rate of over 80%, so it’s encouraging data for an aggressive subset of breast cancer.”

Treatment-related adverse events (TRAEs) occurred in all 26 patients, and grade 3 or higher TRAEs occurred in 34.6% of patients. TRAEs included stomatitis, anemia, nausea, and decreased neutrophil and white blood cell count.¹

DB-1305/BNT325 is still being evaluated in combination with BNT327 for treating patients with TNBC, which Hamilton says, in addition to the monotherapy, expands options for patients with breast cancer.¹

This transcript was lightly edited. Captions are auto-generated.

Transcript

Why are pretreated TNBC patients without prior sacituzumab exposure such an important unmet-need group for this trial?

Unlike what we saw at ESMO, where we saw 1st-line triple-negative breast cancer, this was a more heavily pretreated population. This was a phase 1/2 trial, and so everyone here with triple-negative breast cancer had already received at least 2 prior lines of therapy—3rd-line, and beyond, essentially. That's important to take into account when we're looking at the efficacy and how much activity we saw here.

What was presented on this particular poster was 26 patients with triple-negative breast cancer who had not seen prior sacituzumab govitecan. If you notice, on this poster, we enrolled multiple other cohorts. There was a triple-negative cohort that had seen sacituzumab govitecan, as well as a lot of other tumors. In fact, over 400 patients have been treated on this protocol. But again, this is the subset of 26 that had triple-negative breast cancer and hadn't seen sacituzumab govitecan.

This is the population, and this is a high unmet need. Triple-negative is certainly our most aggressive phenotype of breast cancer now, so new therapies are needed in this area.

How do early response and disease-control rates compare with other TROP2-directed ADCs or standard TNBC options?

I think we can't really compare this directly to the ASCENT-03 or TROPION-Breast02 that we saw at ESMO this year, again, because that was a 1st-line population, and this is really a 3rd-line and beyond population. But it probably does compare to those original ASCENT trials that were at least 2 priors before sacituzumab govitecan got approved.

I think you bring up a great point that the response rate of about 34% actually compares quite favorably, for example, with single-agent chemotherapy and 3rd-line triple-negative breast cancer. We'd probably be thinking our response rate would be less than 15%, so that's really more than a doubling. And in addition to that, we had a disease control rate of over 80%, so it’s encouraging data for an aggressive subset of breast cancer.

How could these findings shape the future of TROP2-targeted ADC development in TNBC and other tumor types?

I think one of the important takeaways is that TROP2 is highly expressed in breast cancers. This is not a target that we need to test for. All patients are eligible for this target because it's widely expressed, and the takeaway is that not all of these drugs are the same. We have ones that are given on day 1 and day 8. We have ones that are given just once every 3 weeks. We have ones that have more prominent neutropenia and diarrhea. We have ones that have more prominent stomatitis. There really are some differences between these drugs, although they all hit the same target, and having some options is definitely desirable for our patients.

References:

1. Hamilton E, Yang H, Shi J, et al. 557P First clinical data of DB-1305/BNT325 (TROP2 antibody-drug conjugate [ADC]) in patients (pts) with pretreated triple-negative breast cancer (TNBC): Efficacy and safety data from a phase 1/2 trial. Ann Oncol. 2025;36:(439). doi:10.1016/j.annonc.2025.08.980

2. Bardia A, Mayer I, Vahdat L, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med. 2019;380(8):741-751. doi:10.1056/NEJMoa1814213