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Palbociclib

Protein Kinase Inhibitors

Enzyme Inhibitors

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).

Palbociclib (75, 100, 125 milligram [mg])

H3B-6545 (150, 300, 450 mg)

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.

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

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

Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Eisai Inc.

Participants received palbociclib 100 milligram (mg) capsule, orally, once daily (QD) from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.

H3B-6545 300 mg + Palbociclib 100 mg

Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 300 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.

H3B-6545 300 mg + Palbociclib 125 mg

Participants received palbociclib 125 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.

H3B-6545 450 mg + Palbociclib 125 mg

Participants received palbociclib 100 mg capsule, orally, QD from Days 1 to 21 followed by H3B-6545 450 mg capsule, orally, QD from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 was administered on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.

H3B-6545 450 mg + Palbociclib 100

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The Full Analysis Set (FAS) included all participants who received at least one dose of study drug.

Eisai Medical Information

H3B-6545

Participants received palbociclib (100 mg, 125 mg) from Days 1 to 21 followed by H3B-6545 (300 mg, 450 mg), from Days 9 to 28 in Cycle1. In all 28 days subsequent cycles, palbociclib was administered on Days 1 to 21, and H3B-6545 on Days 1 to 28 until disease progression, development of unacceptable toxicity, or withdrawal of consent.

All Participants

The Dose Evaluable Set (DES) included all participants who were evaluated for DLTs in dose escalation part.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	Receptors, Estr... Genes, Erbb-2 Breast Neoplasm...	Palbociclib (75... H3B-6545 (150, ...	18 Years -	Eisai Inc.
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	Receptors, Estr... Genes, Erbb-2 Breast Neoplasm...	Palbociclib (75... H3B-6545 (150, ...	18 Years -	Eisai Inc.

Spots Global Cancer Trial Database for palbociclib (75, 100, 125 milligram [mg])