Compelling Sacituzumab Govitecan Data in mTNBC Add to FDA Approval Hopes

Julie R. Gralow, MD

Julie R. Gralow, MD

Treatment with sacituzumab govitecan (IMMUNO-132) resulted in “compelling evidence of efficacy” in patients with metastatic triple-negative breast cancer (mTNBC), leading to an early halt of the phase III ASCENT study, announced Immunomedics in a press release.¹

“Triple-negative breast cancer is a disease with extremely limited treatment options beyond classic chemotherapy. The remarkable results we observed across multiple endpoints in the ASCENT study warranted early discontinuation of the trial and are indicative of a potentially major advance in the treatment of this devastating disease that affects younger women and African American women at higher rates. I look forward to the release of the full and final analyses of these study data when they are available for public presentation,” said Julie R. Gralow, MD, Jill Bennett Endowed Professor of Breast Cancer, University of Washington School of Medicine; and member, Fred Hutchinson Cancer Research Center, in a statement.

The ASCENT trial acts as a confirmatory dataset to the results seen in the phase I/II trial, which were published in theNew England Journal of Medicine.²

In the heavily pretreated population, sacituzumab govitecan achieved durable objective responses.

Out of 108 patients, the response rate was 33.3%, which included complete responses in 2.8% of patients, per local assessment. Partial responses were achieved in 30.6% of patients, per investigator assessment. Additionally, there was a 37.0% rate of stable disease and 25.9% of patients had progressive disease. The clinical benefit rate observed was 45.4%, which included stable disease for at least 6 months.

Among the 39 patients who responded to treatment, the median time to response was 2.0 months (range, 1.6-13.5) and there was a 7.7-month median duration of response ([DOR]; 95% CI, 4.9-10.8). Data were also assessed by blinded independent review, which showed a similar response rate of 34.3% (95% CI, 25.4%-44.0%) and median DOR of 9.1 months (95% CI, 4.6-11.3). According to local assessment, sacituzumab govitecan had a 59.7% estimated probability of eliciting response at 6 months. The estimated probability that patients would respond to treatment at 12 months was 27.0%.

By the data cutoff date, long-term responses over 12 months (range, 12.7-30.4) were seen in 6 patients.

Subgroup analyses were conducted for patients of various ages groups, metastatic disease status, number of previous therapies, and the presence or absence of visceral metastases. No differences in response were observed across these subgroups. Investigators led by Aditya Bardia, MD,

noted, however, that the subgroup analysis was conducted in a small group of patients and should be interpreted with caution.

Disease progression was observed in 87% of patients (n = 94), and death occurred in 71.3% of patients (n = 77), at the time of data cutoff. The median progression-free survival (PFS) was 5.5 months (95% CI, 4.1-6.3), and the estimated probability of PFS was 41.9% at 6 months and 15.1% at 12 months. Median overall survival (OS) was 13.0 months (95% CI, 11.2-13.7), with an estimated probability of survival of 78.5% at 6 months and 51.3% at 12 months.

Investigators evaluated the duration of previous therapy versus therapy in the study to determine how responses to treatment were impacted by the aggressiveness of treatment. It was discovered that the median duration of treatment with sacituzumab govitecan (5.1 months) was twice that of previous therapies (2.5 months).

In terms of safety, the most common any-grade adverse events (AEs) were nausea (67%), neutropenia (64%), diarrhea (62%), fatigue (55%), and anemia (50%). Grade 3 or higher AEs were also observed in the study, with the most common (>5%) being neutropenia (n = 45), anemia (n = 12), and a decreased white-cell count (n = 2).

In 44% of patients, AEs led to an interruption in treatment, most often due to neutropenia. Three percent of patients discontinued treatment due to AEs. Overall, 4 patients died during treatment.

In ASCENT, patients with relapsed or refractory TNBC were randomized 1:1 to receive either sacituzumab govitecan or treatment of physician’s choice. Sacituzumab govitecan was administered at a dose of 10 mg/kg. The study is ongoing but is no longer recruiting patients.

A previously resubmitted Biologic License Application for sacituzumab govitecan as treatment of patients with mTNBC who have received at least 2 prior therapies for metastatic disease is being reviewed by the FDA for approval. The Prescription Drug User Fee Act target action date is June 2, 2020.¹

References

1. Immunomedics announces ASCENT study to be stopped for compelling efficacy [news release]. Morris Plains, New Yrk: Immunomedics; April 6, 2020. https://bit.ly/2UKp8yi. Accessed April 6, 2020.
2. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer.N Engl J Med. 2019;380:741-51. DOI: 10.1056/NEJMoa1814213