IMMU-132 (sacituzumab govitecan) was well-tolerated with durable responses for patients with heavily pretreated metastatic triple-negative breast cancer (TNBC), according to the findings from an ongoing phase 1/2 study presented at the 2016 San Antonio Breast Cancer Symposium (SABCS).
In the single-arm trial, the confirmed objective response rate (ORR) was 30 percent with IMMU-132, and the duration of response was 8.9 months. The median progression-free survival was 6.0 months and the median overall survival was 16.6 months.
"The findings are truly outstanding," said senior study author Linda T. Vahdat, M.D., M.B.A., from Weill Cornell Medicine and NewYork-Presbyterian Hospital. "The confirmed response rate is near 30 percent, and what's really striking is that this is a group of patients with a median of five prior regimens for breast cancer—it is a very heavily pretreated population."
IMMU-132 is an antibody-drug conjugate that consists of the active metabolite of irinotecan, SN-38, linked with a humanized IgG antibody targeted against TROP-2, a cell-surface glycoprotein that is expressed in more than 90 percent of TNBC. In the study, 89 percent of assessable patients (46 patients) had moderate (2+) to strong (3+) TROP-2 expression. In most cases, this expression was seen in 50 percent or more of tumor cells.
The ongoing study enrolled 69 patients with relapsed/refractory metastatic TNBC. The median age of patients was 56 years (range, 31-81). IMMU-132 was administered at 10 mg/kg on days one and eight of each 28-day cycle. A median of 14 doses were administered (range, 1-67) over a median treatment duration of 5.3 months (range, 0.2-23.1).
Patients had an ECOG performance status of 0 (33 percent) and 1 (67 percent) and the primary stage at initial diagnosis was 1 to 2 (55 percent), 3 (30 percent), and 4 (14 percent). Patients had received a median of five prior therapies (range, 1-12), most commonly taxanes (97 percent), cyclophosphamide (91 percent), anthracyclines (84 percent) and platinum agents (70 percent). The most common sites of disease at study entry were the lymph nodes (62 percent), lung (51 percent), liver (43 percent), chest (41 percent) and bone (30 percent).
The complete response (CR) rate with IMMU-132 was 3 percent and the partial response (PR) rate was 28 percent. Additionally, 45 percent of patients had stable disease (SD), with 16 percent of the responses lasting for at least six months. The clinical benefit rate (CR + PR + SD after at least six months) was 46 percent.
After a median follow-up of 16.6 months, seven patients continued to receive therapy, with six continuing to respond at the time of the analysis. There were three durable responses that lasted 13 to 21 months.
"These aren't just flash in the pan type of responses, they are actually quite durable," said Vahdat. "When you have a drug that you can keep someone on in triple-negative breast cancer for almost a year you get excited, because the median survival in TNBC is a little under a year."
Overall, 70 percent of patients treated with IMMU-132 had some reduction in tumor size from baseline. There were 23 patients with tumor reduction of 30 percent or more (two confirmed CRs, 19 confirmed PRs, and two unconfirmed PRs).
The most common grade 3 or higher adverse events (AEs) were neutropenia (39 percent), with febrile neutropenia occurring in 7 percent of patients. Dose reductions were required for 19 percent of patients in the first two cycles, primarily related to neutropenia. Further reductions were needed for 16 percent of patients in later cycles of treatment. There were three discontinuations related to AEs (grade 3 rash/mucositis; grade 3 transient infusion reaction; grade 2 fatigue).
The most common all-grade AEs were nausea (74 percent), neutropenia (68 percent), diarrhea (59 percent), anemia (55 percent), vomiting (51 percent), fatigue (51 percent), alopecia (45 percent), constipation (38 percent), rash (28 percent), abdominal pain (26 percent) and leukopenia (25 percent). The most common grade 3 or higher AEs, regardless of cause, were neutropenia (39 percent), leukopenia (16 percent), anemia (14 percent), diarrhea (13 percent), vomiting (10 percent) and hypophosphatemia (10 percent).
"The drug is very well tolerated, neutropenia is about 39 percent for grade 3/4 and there's very little diarrhea," said Vahdat. "I think the worst side effect is that patients get alopecia."
Data from the ongoing phase 1/2 study will be submitted to the FDA for a potential accelerated approval, according to the poster presented at SABCS. This submission would be completed under a breakthrough therapy designation received in February 2016 for the medication in TNBC following at least two treatments for metastatic disease. A phase 3 study is currently being planned under a special protocol agreement with the FDA.