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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

NCT04288089

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: H3B-6545-G000-102
  • SECONDARY ID: 2019‐004622‐17
  • NCT ID: NCT04288089

Conditions

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

Interventions

DrugSynonymsArms
Palbociclib (75, 100, 125 milligram [mg])Palbociclib + H3B-6545 (Escalation and Expansion)
H3B-6545 (300, 450 mg)Palbociclib + H3B-6545 (Escalation and Expansion)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Palbociclib + H3B-6545 (Escalation and Expansion)Experimental
  • Palbociclib (75, 100, 125 milligram [mg])
  • H3B-6545 (300, 450 mg)

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Ratio of PK Cmax Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
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)
Safety Issue:
Description:Ratio of palbociclib Cmax Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
Measure:Ratio of PK AUC24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
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)
Safety Issue:
Description:Ratio of palbociclib AUC24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
Measure:Ratio of PK C24 Parameter Estimates Between Day 21 (Palbociclib) and Day 8 (Palbociclib)
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)
Safety Issue:
Description:Ratio of palbociclib C24 Day 21/Day 8, is the ratio of palbociclib exposure on Day 21 and palbociclib exposure on Day 8.
Measure:Ratio of PK Cmax Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (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)
Safety Issue:
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.
Measure:Ratio of PK AUC24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (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)
Safety Issue:
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.
Measure:Ratio of PK C24 Parameter Estimates Between Day 21 (H3B-6545) and Day 28 (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)
Safety Issue:
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.
Measure:Objective Response Rate (ORR)
Time Frame:From first dose of study drug up to Month 24
Safety Issue:
Description:ORR is defined as the percentage of participants achieving a best overall response 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.
Measure:Duration of Response (DoR)
Time Frame:From the date of first documented CR/PR until the PD or death, whichever occurs first (up to Month 24)
Safety Issue:
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.
Measure:Disease Control Rate (DCR)
Time Frame:From first dose of study drug up to Month 24
Safety Issue:
Description:DCR is defined as the percentage of participants achieving a best response of CR, PR, or stable disease (SD). The DCR will be assessed according to RECIST v1.1.
Measure:Progression-free Survival (PFS)
Time Frame:From first dose of study drug until first documentation of PD or death, whichever occurs first (up to Month 24)
Safety Issue:
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).
Measure:Overall Survival (OS)
Time Frame:From the date of first dose to the date of death from any cause (up to Month 24)
Safety Issue:
Description:OS is defined as the time from first dose date to the date of death from any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:H3 Biomedicine Inc.

Trial Keywords

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

Last Updated

March 11, 2020