Abstract 5999
Background
HA in the tumor microenvironment can inhibit the effectiveness of anticancer agents. The novel biologic PEGPH20 degrades pathological HA accumulation. EM is a microtubule inhibitor approved for the treatment of pts with MBC who previously received ≤2 lines of systemic anticancer therapy for metastatic disease. Preclinical data showed the PEGPH20+EM combination resulted in enhanced anti-tumor effectiveness in HAaccumulating, triple-negative breast cancer (TNBC) xenografts. The primary objective of this Phase 1b study (NCT02753595) was to determine safety, tolerability and RP2D of PEGPH20+EM in pts with HER2neg MBC previously treated with ≤2 lines of systemic anticancer therapy in the metastatic setting.
Methods
Overall, 14 enrolled pts were treated IV at 2 PEGPH20 dose levels (DL1=3 µg/kg or DL0=1.6 µg/kg on D1, D7) + EM 1.4 mg/m2 on D1, D8 of a 21day cycle. 5 pts were treated at DL1, with 2 DLTs observed (G3 muscle cramp, G3 knee/leg pain); 6 pts were enrolled in DL0 with no further DLTs. An additional 3 pts were enrolled at DL0 (RP2D).
Results
All 14 pts were evaluable for safety and efficacy. Median age was 53 years (33–78 years); 14% (2/14) of pts had TNBC. Median number of treatment cycles was 6.0. Drug-related TEAEs occurred in 86% of pts during PEGPH20+EM therapy. 79% of pts had G ≥ 3 TEAEs. There were 3 SAEs (1 in DL1 and 2 in DL0). As of April 2018, the individual safety profile was as expected for PEGPH20 and EM; no new significant safety signals identified. Key pt characteristics and BORs are shown below. Out of the 5 pts with confirmed PR, 3 had 1 prior and 2 had no prior systemic anticancer therapy in the metastatic setting.Table: 311P
| Category | PEGPH20 (3 µg/kg)/ | PEGPH20 (1.6µg/kg)/ | Total |
|---|---|---|---|
| EM (1.4 mg/m2) | EM (1.4 mg/m2) | ||
| (n = 5) | (n = 9) | (N = 14) | |
| Enrollment Strata – n (%) | |||
| TNBC | 0 (0) | 2 (22) | 2 (14) |
| ER and/or PRo-positive | 5 (100) | 7 (78) | 12 (86) |
| ECOG Status – n (%) | |||
| 0 | 4 (80) | 4 (44) | 8 (57) |
| 1 | 1 (20) | 5 (56) | 6 (43) |
| No. Prior Systemic Anticancer Therapy in Metastatic Setting – n (%) | |||
| 0 | 1 (20) | 4 (44) | 5 (36) |
| 1 | 3 (60) | 5 (56) | 8 (57) |
| 2 | 1 (20) | 0 (0) | 1 (7) |
| Confirmed BOR – n (%) | |||
| CR | 0 (0) | 0 (0) | 0 (0) |
| PR | 2 (40) | 3 (33) | 5 (36) |
| SD | 1 (20) | 2 (22) | 3 (21) |
| PD | 1 (20) | 3 (33) | 4 (29) |
| Not evaluable/Unknown | 1 (20) | 1 (11) | 2 (14) |
| ORR (CR+PR) – n (%) | 2 (40) | 3 (33) | 5 (36) |
| DCR (CR+PR+SD) – n (%) | 3 (60) | 5 (56) | 8 (57) |
Abbreviations: BOR=best overall response; CR=complete response; DCR=disease control rate; ECOG=Eastern Cooperative Oncology Group; EM=eribulin mesylate; ER=estrogen receptor; MBC=metastatic breast cancer; ORR=objective response rate; PD=progressive disease; PEGPH20=pegvorhyaluronidase alfa; PR=partial response; PRo=progesterone receptor; SD=stable disease; TNBC=triple-negative breast cancer
Conclusions
These early results are encouraging with a 36% ORR and 57% DCR, suggesting that PEGPH20 + anti-breast cancer agents such as EM warrant further investigation in pts with HER-2 neg MBC. A complete dataset is expected in October 2018.
Clinical trial identification
NCT02753595.
Legal entity responsible for the study
Eisai, Inc.
Funding
Eisai, Inc. in collaboration with Halozyme Therapeutics, Inc.
Editorial Acknowledgement
Editorial assistance provided by Paragon, Knutsford, UK.
Disclosure
C. Savulsky, W. Zhu, P. Iyer, D. Xing: Employee: Eisai C. Berman, N.A. Lokker: Employee: Halozyme Therapeutics. All other authors have declared no conflicts of interest.
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