IMMU-132 Produces Early, Durable Responses in Metastatic Triple-Negative Breast Cancer

Progression-free survival with IMMU-132 increases from an average of 3.5 months to 16.6 months in patients with breast cancer.

The antibody-drug conjugate sacituzumab govitecan (IMMU-132) demonstrated meaningful clinical benefit in heavily-pretreated patients with metastatic triple-negative breast cancer (TNBC). These findings were published in the Journal of Clinical Oncology.

The single-arm phase 2 study included 69 patients with TNBC, according to a press release. The overall confirmed objective response rate (ORR) was 30%, with 2 patients having complete remissions and 19 patients achieving partial responses (PRs).

With the median time to an ORR of 1.9 months, the responses occurred early, and 13 of 21 confirmed responders demonstrated a PR or better at the first response assessment at 8 weeks. Forty-three percent of confirmed responses continued treatment for at least 12 months, and the median duration of response was 8.9%.

Overall, 69.5% of patients had a reduction in tumor burden, according to the release.

Although the study population was comprised of heavily pretreated patients, the median progression-free survival (PFS) was 16.6 months.

“These results are very encouraging given the impressive clinical activity seen in a refractory setting, durability of responses, and the safety profile,” lead author Aditya Bardia, MD, MPH, said in the release. “The average PFS is about 3.5 months for standard agents, including cisplatin, capecitabine, nab-paclitaxel, and eribulin, as reported in earlier metastatic TNBC trials.”

Interestingly, IMMU-132 was administered to 4 patients who received prior therapy with an immune checkpoint inhibitor, according to the authors. Although only 1 of 4 patients had responded briefly to the checkpoint inhibitor, 3 patients had a PR with IMMU-132 after the checkpoint inhibitor therapy failed. The findings suggest that the ADC and PD-1/PD-L1 antibodies may represent non-cross-resistant therapeutic options for a potential combination therapy, which requires more research.

“Studies have consistently shown that IMMU-132 is a viable option for patients who have this very aggressive form of cancer,” said senior author Dr Linda T. Vahdat. “The most common side effect [sic] reported is hair loss, which is expected, and the drug was effective in shrinking tumors for most TNBC patients.”

Prolonged therapy with up to 67 doses of IMMU-132 administered over 23 months was well tolerated in patients, and no evidence of an immune response to the ADC. There were no treatment-related life-threatening or fatal events reported, and the toxicity profile was generally mild and manageable, with the primary dose-limiting toxicity being neutropenia.

Grade 3 or higher adverse events included neutropenia, leukopenia, anemia, and diarrhea. The authors noted that few patients had febrile neutropenia or severe diarrhea, suggesting that ADC toxicities appear to be related primarily to the drug SN-38.

“Immu-132 continues to produce meaningful clinical benefit in metastatic TNBC patients who are exhausting standard treatment options,” Cynthia L. Sullivan, president and chief executive officer of Immunomedics, said in the release. “We are working diligently with the FDA to make this valuable product candidate available to this group of patients as soon as possible. Blinded, independent radiological assessments are ongoing, and so far, show a high concordance with local tomography findings.”