A Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive Human Epidermal Growth Factor Receptor-2 (HER2)-Negative Breast Cancer

NCT04288089 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: H3B-6545-G000-1022019-004622-17
• Study Type: interventional
• Target: 31
• Locations: 2 countries
• Sites: 8

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of H3B-6545 and palbociclib when administered in combination in order to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of this combination in women with advanced or metastatic estrogen receptor-positive (ER+) HER2- breast cancer.

Conditions

Receptors, Estrogen; Genes, Erbb-2; Breast Neoplasms

Keywords

H3B-6545; Palbociclib; Metastatic Estrogen Receptor-Positive; HER2-Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of H3B-6545 and Palbociclib

  The MTD was defined as the highest dose at which no more than 1 of 6 participants experienced a Dose-Limiting Toxicity (DLT) in the dose cohort. DLT was graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs were defined as the following events that occurred in Cycle 1, for which a causal relationship with the study drug could not be ruled out: febrile neutropenia; Grade 4 neutropenia that was not resolved within 7 days; Grade 4 thrombocytopenia; Grade 3 thrombocytopenia lasting greater than (\>) 7 days or associated with clinically significant bleeding; Grade 4 vomiting and diarrhea; Grade 3 vomiting and diarrhea lasting \> 72 hours despite treatment; Grade 4 electrolyte abnormality or Grade 3 abnormality lasting \> 24 hours; Grade 3 or 4 serum creatinine or bilirubin increase; Grade 4 biochemistry or Grade 3 lasting \> 7 days; Grade 4 or Grade 3 or intolerable grade 2 toxicities of any non-hematologic adverse event.

  Cycle 1 (Cycle length = 28 Days)

Secondary Outcomes (16)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  From first dose up to 28 days after the last dose of study drug (up to Month 48)

• AUC(0-t): Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Point for Palbociclib and H3B-6545

  Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

• Cmax: Maximum Observed Plasma Concentration for Palbociclib and H3B-6545

  Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

• Tmax: Time to Reach the Cmax for Palbociclib and H3B-6545

  Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

• C24: Plasma Concentration at 24 Hour Post-dose for Palbociclib and H3B-6545

  Dose Escalation Part: Cycle 1 Days 8, 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)

Study Arms (1)

Palbociclib + H3B-6545 (Dose Escalation and Dose Expansion)

EXPERIMENTAL

Participants will receive Palbociclib 75, 100, 125 milligram (mg) capsules or tablets, orally, once daily from Days 1 to 21 followed by 7 days off treatment in 28-day cycles along with H3B-6545 150, 300, 450 mg capsules or tablets, orally, once daily from Days 1 to 28 in 28-day cycles in dose escalation part. Based on MTD or RP2D determined for H3B-6545 in combination with palbociclib in dose escalation part, participants will continue to receive study treatment in dose expansion part until PD, development of unacceptable toxicity, or withdrawal of consent (up to 24 months).

Drug: Palbociclib (75, 100, 125 milligram [mg]); Drug: H3B-6545 (150, 300, 450 mg)

Interventions

H3B-6545 (150, 300, 450 mg) DRUG

H3B-6545 orally, QD.

Palbociclib + H3B-6545 (Dose Escalation and Dose Expansion)

Palbociclib (75, 100, 125 milligram [mg]) DRUG

Palbociclib orally, once daily (QD).

Palbociclib + H3B-6545 (Dose Escalation and Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ER+ HER2- locally advanced, recurrent, or metastatic breast cancer, as per local laboratory
• Prior therapy in the advanced/metastatic setting
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Has adequate bone marrow and organ function

You may not qualify if:

• Uncontrolled significant active infections
• Major surgery or other locoregional treatment within 4 weeks before the 1st dose of study drug
• Inability to take oral medication or presence of malabsorption
• Active cardiac disease or a history of cardiac dysfunction
• Evidence of ongoing Alcohol or Drug Abuse

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (8)

Florida Cancer Specialists South - SCRI - PPDS

Sarasota, Florida, 34232, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Saint Luke's Cancer Institute

Kansas City, Missouri, 64111, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Tennessee Oncology, PLLC - SCRI - PPDS

Nashville, Tennessee, 37203, United States

Location

Royal Marsden NHS Foundation Trust

London, United Kingdom

Location

Sarah Cannon Research Institute UK - SCRI

London, United Kingdom

Location

Royal Marsden NHS Foundation Trust

Sutton, United Kingdom

Location

Related Publications (1)

• Furman C, Puyang X, Zhang Z, Wu ZJ, Banka D, Aithal KB, Albacker LA, Hao MH, Irwin S, Kim A, Montesion M, Moriarty AD, Murugesan K, Nguyen TV, Rimkunas V, Sahmoud T, Wick MJ, Yao S, Zhang X, Zeng H, Vaillancourt FH, Bolduc DM, Larsen N, Zheng GZ, Prajapati S, Zhu P, Korpal M. Covalent ERalpha Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer. Mol Cancer Ther. 2022 Jun 1;21(6):890-902. doi: 10.1158/1535-7163.MCT-21-0378.

  PMID: 35642432 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; H3B-6545

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2020
• First Posted: February 27, 2020
• Study Start: April 1, 2020
• Primary Completion: September 16, 2022
• Study Completion (Estimated): March 31, 2027
• Last Updated: February 27, 2026
• Results First Posted: March 22, 2024

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

US (5); GB (3)