NCT04669587

ER+/HER2- Locally Advanced or Metastatic Breast Cancer (ENZENO Study)

A Phase 1/2, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Preliminary Antitumor Activity, Pharmacokinetics, and Pharmacodynamics of ZB716 as Monotherapy and in Combination With Palbociclib in Patients With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 106 (estimated)
• Sponsor: EnhancedBio USA Inc. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Estrogen Receptor-Positive
• HER2-Negative
• Locally Advanced Breast Cancer
• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	ZB716	Pharmaceutical form: capsule Route of administration: oral
DRUG	Palbociclib	Pharmaceutical form: capsule Route of administration: oral

Timeline

• Start date: 2021-07-26
• Primary completion: 2023-01-31
• Completion: 2024-01-31
• First posted: 2020-12-17
• Last updated: 2022-03-22

Locations

8 sites across 2 countries: United States, South Korea

Regulatory

• FDA-regulated drug study