Clinical trial NCT04288089: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Receptors, Estrogen
Genes, Erbb-2
Breast Neoplasms
Keywords: H3B-6545
Palbociclib
Metastatic Estrogen Receptor-Positive
HER2-Negative Breast Cancer
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2020-02-27
Enrollment: 31
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of H3B-6545 and Palbociclib
timeFrame: Cycle 1 (Cycle length = 28 Days)
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose up to 28 days after the last dose of study drug (up to Month 48)
measure: AUC(0-t): Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Point for Palbociclib and H3B-6545
timeFrame: 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)
measure: Cmax: Maximum Observed Plasma Concentration for Palbociclib and H3B-6545
timeFrame: 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)
measure: Tmax: Time to Reach the Cmax for Palbociclib and H3B-6545
timeFrame: 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)
measure: C24: Plasma Concentration at 24 Hour Post-dose for Palbociclib and H3B-6545
timeFrame: 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)
measure: Ratio of Pharmacokinetic (PK) Cmax Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
timeFrame: Dose Escalation Part: Cycle 1 Days 8 and 21: 0-24 hours postdose
measure: Ratio of PK AUC24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
timeFrame: 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)
measure: Ratio of PK C24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
timeFrame: 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)
measure: Ratio of PK Cmax Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545)
timeFrame: 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)
measure: Ratio of PK AUC24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545)
timeFrame: 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)
measure: Ratio of PK C24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (H3B-6545)
timeFrame: 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)
measure: Objective Response Rate (ORR)
timeFrame: From first dose of study drug up to Month 48
measure: Duration of Response (DoR)
timeFrame: From the date of first documented CR/PR until the PD or death, whichever occurs first (up to Month 48)
measure: Clinical Benefit Rate (CBR)
timeFrame: From the first dose of study drug until disease progression or death, whichever occurs first (up to Month 48)
measure: Progression-free Survival (PFS)
timeFrame: From first dose of study drug until first documentation of PD or death, whichever occurs first (up to Month 48)
measure: Overall Survival (OS)
timeFrame: From the date of first dose to the date of death from any cause (up to Month 48)
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists South - SCRI - PPDS
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC - SCRI - PPDS
state: Tennessee
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK - SCRI
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
Study officials:
References:
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.