ER+/HER2- Locally Advanced or Metastatic Breast Cancer (ENZENO Study)
Status:
Recruiting
Trial end date:
2024-01-31
Target enrollment:
Participant gender:
Summary
For patients with ER-positive, HER2-negative breast cancer, blockage of the ER pathway has
been proven to be an effective anticancer approach. These patients showed good response to
endocrine therapy.
Fulvestrant, the approved SERD as monotherapy or in combination with CDK4/6 inhibitors,
showed superior clinical benefit compared to other endocrine therapies. Fulvestrant exhibits
differential mechanism of action from other endocrine therapy, such as tamoxifen, aromatase
inhibitors, which indicates that direct blockage of ER might derive better clinical activity.
However, due to its route of administration by intramuscular injection, the clinical
application is limited, especially with long term use. In addition, a higher dose of
fulvestrant at 500 mg showed better overall survival than the lower dose at 250 mg,
suggesting that more profound ER pathway modulation could derive better clinical benefit.
Therefore, a SERD with improved oral bioavailability and good safety profile which enables
its overdose is anticipated to achieve a more satisfactory clinical outcome with better
compliance of clinical use.
Preclinical data indicates that ZB716 is a novel orally bioavailable, selective ERα degrader
with full ER antagonism that demonstrates superior properties than Fulvestrant. Thus, it has
a potential to be effective therapy for patients with ER-positive breast cancer.
This is the first time ZB716 will be administered to humans. The principal aim of this study
is to obtain safety and tolerability data when ZB716 is administered orally as monotherapy
and in combination with palbociclib to subjects with ER-positive, HER2 negative advanced
breast cancer. This information, together with the PK data, will help establish the doses and
dosing regimen suitable for future studies in patients. The PD effect of ZB716 on the select
biomarkers for cytochrome P450 (CYP)3A4 induction (4β hydroxycholesterol) and expression of
ER, PgR, and Ki67 will also be investigated. The effect of ZB716 on antitumor activity as
measured by objective response rate (ORR), clinical benefit rate (CBR), duration of response
(DOR), and PFS rate will also be investigated. The study will also investigate the effects of
food on the PK of ZB716 monotherapy.