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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

Primary Purpose

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

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Palbociclib (75, 100, 125 milligram [mg])
H3B-6545 (150, 300, 450 mg)
Sponsored by
Eisai Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Receptors, Estrogen focused on measuring H3B-6545, Palbociclib, Metastatic Estrogen Receptor-Positive, HER2-Negative Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

  • Florida Cancer Specialists South - SCRI - PPDS
  • Massachusetts General Hospital
  • Saint Luke's Cancer Institute
  • Comprehensive Cancer Centers of Nevada
  • Tennessee Oncology, PLLC - SCRI - PPDS
  • Royal Marsden NHS Foundation Trust
  • Sarah Cannon Research Institute UK - SCRI
  • Royal Marsden NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

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).

Outcomes

Primary Outcome Measures

Dose Escalation Part: MTD and/or RP2D of Palbociclib and H3B-6545

Secondary Outcome Measures

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
AUC(0-t): Area Under the Plasma Concentration-time Curve from Time 0 to the Last Measurable Point for Palbociclib and H3B-6545
Cmax: Maximum Observed Plasma Concentration for Palbociclib and H3B-6545
Tmax: Time to Reach the Cmax for Palbociclib and H3B-6545
C24: Plasma Concentration at 24 hour Post-dose for Palbociclib and H3B-6545
Ratio of Pharmacokinetic (PK) Cmax Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
Ratio of palbociclib Cmax Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
Ratio of PK AUC24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
Ratio of palbociclib AUC24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
Ratio of PK C24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
Ratio of palbociclib C24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
Ratio of PK Cmax Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545)
Ratio of palbociclib Cmax Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28.
Ratio of PK AUC24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545)
Ratio of H3B-6545 AUC24 Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28.
Ratio of PK C24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545)
Ratio of H3B-6545 C24 Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28.
Objective Response Rate (ORR)
ORR is defined as the percentage of participants achieving a best overall response (BOR) of confirmed partial response (PR) or complete response (CR). The ORR will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Duration of Response (DoR)
DoR is defined as the time from the date of the first documented CR/PR until the first documentation of disease progression (PD) or death, whichever comes first. The DoR will be assessed according to RECIST version 1.1.
Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants with BOR of PR, CR, or durable stable disease (SD) (duration of SD greater than or equal to 23 weeks). Duration of SD is defined as the time from the date of first dose to the date of the first documentation of disease progression or death, whichever occurs first. It will be calculated for participants whose BOR is SD. The CBR will be assessed according to RECIST version 1.1.
Progression-free Survival (PFS)
PFS is defined as the time from the first dose date to the date of the first documentation of PD or death (whichever occurs first).
Overall Survival (OS)
OS is defined as the time from first dose date to the date of death from any cause.

Full Information

First Posted
February 26, 2020
Last Updated
July 31, 2023
Sponsor
Eisai Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04288089
Brief Title
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
Official Title
An Open-Label Multicenter Phase 1b Study of H3B-6545 in Combination With Palbociclib in Women With Advanced or Metastatic Estrogen Receptor-Positive HER2-Negative Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 1, 2020 (Actual)
Primary Completion Date
September 16, 2022 (Actual)
Study Completion Date
March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Receptors, Estrogen, Genes, Erbb-2, Breast Neoplasms
Keywords
H3B-6545, Palbociclib, Metastatic Estrogen Receptor-Positive, HER2-Negative Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Palbociclib + H3B-6545 (Dose Escalation and Dose Expansion)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Palbociclib (75, 100, 125 milligram [mg])
Intervention Description
Palbociclib orally, once daily (QD).
Intervention Type
Drug
Intervention Name(s)
H3B-6545 (150, 300, 450 mg)
Intervention Description
H3B-6545 orally, QD.
Primary Outcome Measure Information:
Title
Dose Escalation Part: MTD and/or RP2D of Palbociclib and H3B-6545
Time Frame
From Cycle 1 Day 9 up to Cycle 2 Day 8 (Each cycle length is equal to [=] 28 days)
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame
From first dose up to 28 days after the last dose of study drug (up to Month 24)
Title
AUC(0-t): Area Under the Plasma Concentration-time Curve from Time 0 to the Last Measurable Point for Palbociclib and H3B-6545
Time Frame
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)
Title
Cmax: Maximum Observed Plasma Concentration for Palbociclib and H3B-6545
Time Frame
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)
Title
Tmax: Time to Reach the Cmax for Palbociclib and H3B-6545
Time Frame
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)
Title
C24: Plasma Concentration at 24 hour Post-dose for Palbociclib and H3B-6545
Time Frame
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)
Title
Ratio of Pharmacokinetic (PK) Cmax Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
Description
Ratio of palbociclib Cmax Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
Time Frame
Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)
Title
Ratio of PK AUC24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
Description
Ratio of palbociclib AUC24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
Time Frame
Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)
Title
Ratio of PK C24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
Description
Ratio of palbociclib C24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
Time Frame
Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)
Title
Ratio of PK Cmax Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545)
Description
Ratio of palbociclib Cmax Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28.
Time Frame
Dose Escalation Part: Cycle 1 Days 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)
Title
Ratio of PK AUC24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545)
Description
Ratio of H3B-6545 AUC24 Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28.
Time Frame
Dose Escalation Part: Cycle 1 Days 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)
Title
Ratio of PK C24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545)
Description
Ratio of H3B-6545 C24 Day 21/Day 28, is the ratio of H3B-6545 exposure on Day 21 and H3B-6545 exposure on Day 28.
Time Frame
Dose Escalation Part: Cycle 1 Days 21 and 28: 0-24 hours postdose; Dose Expansion Part: Cycle 1 Day 21: 0-24 hours postdose (Each Cycle length=28 days)
Title
Objective Response Rate (ORR)
Description
ORR is defined as the percentage of participants achieving a best overall response (BOR) of confirmed partial response (PR) or complete response (CR). The ORR will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time Frame
From first dose of study drug up to Month 24
Title
Duration of Response (DoR)
Description
DoR is defined as the time from the date of the first documented CR/PR until the first documentation of disease progression (PD) or death, whichever comes first. The DoR will be assessed according to RECIST version 1.1.
Time Frame
From the date of first documented CR/PR until the PD or death, whichever occurs first (up to Month 24)
Title
Clinical Benefit Rate (CBR)
Description
CBR is defined as the percentage of participants with BOR of PR, CR, or durable stable disease (SD) (duration of SD greater than or equal to 23 weeks). Duration of SD is defined as the time from the date of first dose to the date of the first documentation of disease progression or death, whichever occurs first. It will be calculated for participants whose BOR is SD. The CBR will be assessed according to RECIST version 1.1.
Time Frame
From the first dose of study drug until disease progression or death, whichever occurs first (up to Month 24)
Title
Progression-free Survival (PFS)
Description
PFS is defined as the time from the first dose date to the date of the first documentation of PD or death (whichever occurs first).
Time Frame
From first dose of study drug until first documentation of PD or death, whichever occurs first (up to Month 24)
Title
Overall Survival (OS)
Description
OS is defined as the time from first dose date to the date of death from any cause.
Time Frame
From the date of first dose to the date of death from any cause (up to Month 24)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Facility Information:
Facility Name
Florida Cancer Specialists South - SCRI - PPDS
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Saint Luke's Cancer Institute
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Tennessee Oncology, PLLC - SCRI - PPDS
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Royal Marsden NHS Foundation Trust
City
London
Country
United Kingdom
Facility Name
Sarah Cannon Research Institute UK - SCRI
City
London
Country
United Kingdom
Facility Name
Royal Marsden NHS Foundation Trust
City
Sutton
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
Citations:
PubMed Identifier
35642432
Citation
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.
Results Reference
derived

Learn more about this trial

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

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