Phase II clinical trial using anti-CD3 x anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) for HER2-negative (0-2+) metastatic breast cancer.

Abstract

1080 Background: This study presents a phase II cell therapy trial in 32 women with metastatic or locally advanced HER2- breast cancer (BrCa) who received infusions of anti-CD3 x anti-HER2 bispecific antibody armed activated T cells (BATs). This phase II study (NCT 01022138) was conducted to determine if BATs infusions could improve time to progression (TTP) and overall survival (OS), as well as to confirm the toxicity profile of BATs. Methods: The phase II included 32 patients with a median of 4 lines of therapy (7 TNBC and 25 HR/PR+ HER2- patients) with an average age of 52.5 years (range 28-75 years). Twenty-one patients had ≥3 lines of prior therapy and 11 patients had 1-2 lines. Peripheral blood mononuclear cells (PBMC) were stimulated with anti-CD3 antibody and expanded in IL-2, armed with HER2Bi, and aliquoted for the clinical trial. Patients received oncologist’s choice of chemotherapy (4 cycles/4 months) followed by 3 infusions of BATs given once per week for 3 weeks and a boost given 12 weeks after the 3rd infusion. Results: Fifteen of 32 (ORR of 46.8%) who had received any cells had stable disease (SD) at 1 month after the last infusion, and 8 of 15 (25%) had SD > 4 months. For patients who completed 3 or 4 infusions (17-83 x 109 BATs), 8 of 31 patients had TTP > 4 months. One patient completed 2 infusions (17 x 109 BATs). There were no dose limiting toxicities (DLTs). Tumor markers decreased in 13 of 23 (56.5%) patients with evaluable markers. The median OS was 13.8, 16.5, and 12.4 months for all, ER/PR+, and TNBC, respectively. OS for all patients with chemosensitive (chemoS) and chemoresistant (chemoR) disease was 14.6 and 8.6 months (NS), respectively. OS for chemoS and chemoR disease in HER2- ER/PR+ patients was 16.5 and 8.6 months (NS), respectively. OS for chemoS and chemoR disease in TNBC patients was 12.4 and 22.6 months, respectively (NS). The median TTP for all, HER2- ER/PR+, and TNBC patients was 2.7, 2.9, and 1.4 months, respectively. Increases in serum IL-2 and IL-12 were associated with BATs infusions. Conclusions: Targeting HER2- tumors was safe. There were trends toward improved survival in patients who were HER2-/ER/PR+ TNBC, patients who were chemoS, was associated with increased TTP and OS in all groups, and was associated with decreased tumor markers in those who received 4 infusions. Immune studies showed evidence for induction of adaptive immunity directed at breast cancer antigens. Targeting metastatic HER2- BrCa with BATs shows promise. Clinical trial information: NCT 01022138.