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

Phase 1Active Not RecruitingNCT04288089

Eisai Inc.31 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Receptors, Estrogen Genes, Erbb-2 Breast Neoplasms

Interventions

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (8)

Florida Cancer Specialists South - SCRI - PPDS

Sarasota, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Saint Luke's Cancer Institute

Kansas City, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Tennessee Oncology, PLLC - SCRI - PPDS

Nashville, Tennessee, United States

Royal Marsden NHS Foundation Trust

London, United Kingdom

Sarah Cannon Research Institute UK - SCRI

London, United Kingdom

Royal Marsden NHS Foundation Trust

Sutton, United Kingdom

Outcomes

Primary Outcomes

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.

Time frame: Cycle 1 (Cycle length = 28 Days)

Secondary Outcomes

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

TEAE was defined as an adverse event (AE) with an onset that had occurred after receiving study drug. An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A serious adverse event (SAE) was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Time frame: 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

Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

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)

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

Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

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)

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

Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

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)

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

Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

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)

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. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Time frame: Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose

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. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

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)

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. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

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)

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. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

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)

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. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

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)

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. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

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)

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. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Time frame: From first dose of study drug up to Month 48

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. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Time frame: From the date of first documented CR/PR until the PD or death, whichever occurs first (up to Month 48)

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. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Time frame: From the first dose of study drug until disease progression or death, whichever occurs first (up to Month 48)

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). Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Time frame: From first dose of study drug until first documentation of PD or death, whichever occurs first (up to Month 48)

Overall Survival (OS)

OS is defined as the time from first dose date to the date of death from any cause. Analysis is not final for this outcome measure, and complete data will be posted at study completion date.

Time frame: From the date of first dose to the date of death from any cause (up to Month 48)