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.
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
| Drug | Synonyms | Arms |
|---|
| 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
| Name | Type | Description | Interventions |
|---|
| 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: | Recruiting |
| Lead Sponsor: | H3 Biomedicine Inc. |
Trial Keywords
- H3B-6545
- Palbociclib
- Metastatic Estrogen Receptor-Positive
- HER2-Negative Breast Cancer
Last Updated
July 16, 2021
