H3B-6545 + Palbociclib for Breast Cancer

Not currently recruiting at 7 trial locations

Overseen By Eisai Medical Information

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: H3 Biomedicine Inc.

Disqualifiers: Infections, Cardiac disease, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medicines, H3B-6545 (an experimental treatment) and palbociclib, to determine the safest dose for treating advanced breast cancer. It focuses on women with advanced or metastatic breast cancer, specifically those with estrogen receptor-positive (ER+) and HER2-negative types. The trial aims to assess the effectiveness and safety of these drugs when used together. Women who have already received treatment for advanced breast cancer and have no major infections or heart problems may be suitable candidates for this trial. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is examining the safety of using H3B-6545 and palbociclib together for treating advanced breast cancer. Previous studies have shown that palbociclib, when combined with other drugs, is safe. For example, in one study with 191 patients, palbociclib was well-tolerated, and patients lived without their cancer worsening for an average of 22.8 months when used as the first treatment.

H3B-6545 is a newer drug, so less information is available about its safety. This trial is in an early stage, meaning researchers are still determining the safest way to use these two drugs together. This phase focuses on understanding side effects and finding the best dose.

Prospective participants should know that the main goal is to ensure the treatment's safety and determine the best way to use it. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about H3B-6545 combined with Palbociclib for breast cancer because it targets the estrogen receptor in a novel way. Unlike traditional hormone therapies that indirectly impact the estrogen pathway, H3B-6545 directly binds to and degrades the estrogen receptor, potentially offering a more effective treatment for patients with hormone receptor-positive breast cancer. Additionally, the combination with Palbociclib, a well-known CDK4/6 inhibitor, might enhance the suppression of cancer cell growth, providing a powerful one-two punch against cancer cells. This unique approach could offer new hope for patients who have not responded well to existing therapies.

What evidence suggests that this treatment might be an effective treatment for breast cancer?

Research has shown that combining H3B-6545 with palbociclib, which participants in this trial will receive, may help treat advanced breast cancer. In a study with 191 patients, those who used palbociclib as their first treatment lived for an average of 22.8 months without their cancer worsening. Palbociclib already works well for certain types of breast cancer, and adding H3B-6545 might enhance its effectiveness. While the researchers are still assessing the safety and tolerability of this combination, these early results suggest it could benefit people with estrogen receptor-positive breast cancer. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for women with advanced or metastatic estrogen receptor-positive, HER2-negative breast cancer. Participants should have had prior therapy in the advanced/metastatic setting and be in good physical condition (ECOG status of 0 or 1). They must also have proper bone marrow and organ function. Women with uncontrolled infections, recent major surgery, issues taking oral medication, substance abuse problems, or active heart disease are not eligible.

Inclusion Criteria

My bone marrow and organs are working well.

I have received treatment for cancer after it spread.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You are currently using alcohol or drugs in a harmful way.

I cannot take pills by mouth or have a problem absorbing food.

I do not have any serious ongoing infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive Palbociclib and H3B-6545 in escalating doses to determine the maximum tolerated dose (MTD)

28 days per cycle

Cycle 1 Days 8, 21 and 28: 0-24 hours postdose

Dose Expansion

Participants continue to receive study treatment at the recommended Phase 2 dose (RP2D) until disease progression or unacceptable toxicity

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 48 months

What Are the Treatments Tested in This Trial?

Interventions

• H3B-6545
• Palbociclib

Trial Overview The study is testing the combination of two drugs: H3B-6545 and Palbociclib at various doses to find the safest and most effective dose level for women with a specific type of advanced breast cancer. The goal is to determine the maximum tolerated dose as well as a recommended dose for future Phase 2 trials.

How Is the Trial Designed?

Group I: Palbociclib + H3B-6545 (Dose Escalation and Dose Expansion) Experimental Treatment 2 Interventions

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).

Who Is Running the Clinical Trial?

H3 Biomedicine Inc.

Lead Sponsor

Trials

7

Recruited

480+

Eisai Inc.

Lead Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Published Research Related to This Trial

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

In a study involving 1723 women with HR+/HER2- advanced or metastatic breast cancer, palbociclib combined with aromatase inhibitors or fulvestrant showed low dose-reduction rates (18.9% and 12.3%, respectively), indicating good tolerability.

The treatment demonstrated favorable progression-free rates (PFR) at 12 months, with 88.1% for palbociclib + AI and 79.8% for palbociclib + fulvestrant, along with high survival rates (97.3% and 97.5%, respectively), suggesting its effectiveness in real-world clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment of patients with palbociclib for HR+/HER2-advanced/metastatic breast cancer: the Europe IRIS study. Mycock, K., Zhan, L., Hart, K., et al.[2022]

Palbociclib is a selective inhibitor of CDK4 and CDK6, which are crucial for cell cycle regulation, and has been approved in the US for use with letrozole as a first-line treatment for advanced breast cancer in postmenopausal women.

Ongoing clinical trials are exploring palbociclib's efficacy in various cancer types, including non-small cell lung cancer and other solid tumors, indicating its potential as a versatile treatment option in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: first global approval. Dhillon, S.[2018]

The FDA approved palbociclib (IBRANCE) for use in men with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, expanding its indications beyond women, based on data from the PALOMA-2 and PALOMA-3 trials.

The approval was supported by safety data from phase I studies and real-world evidence, confirming that palbociclib is a viable treatment option for male patients with this type of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Palbociclib for Male Patients with Metastatic Breast Cancer. Wedam, S., Fashoyin-Aje, L., Bloomquist, E., et al.[2021]

In a study of 191 patients with metastatic breast cancer receiving palbociclib, the median progression-free survival was 22.8 months for first-line treatment, indicating significant efficacy of the drug in delaying disease progression.

While 47% of patients experienced severe neutropenia, the overall survival rate at 24 months was 74.2% for first-line treatment, suggesting that palbociclib is effective but requires monitoring for potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world study of the first use of palbociclib for the treatment of advanced breast cancer within the UK National Health Service as part of the novel Ibrance® Patient Program. Palmieri, C., Musson, A., Harper-Wynne, C., et al.[2023]

Palbociclib is the first CDK4/6 inhibitor approved for treating estrogen receptor-positive, HER2-negative metastatic breast cancer, and it works by selectively inhibiting CDK4 and CDK6, enhancing the effects of anti-estrogens like letrozole and fulvestrant.

Clinical trials show that palbociclib significantly doubles the treatment efficacy of letrozole and fulvestrant while maintaining a manageable safety profile, positively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. Ettl, J., Harbeck, N.[2017]

Citations

1. withpower.com withpower.com/trial/phase-1-breast-neoplasms-3-2020-c1bb5

H3B-6545 + Palbociclib for Breast Cancer In a study of 191 patients with metastatic breast cancer receiving palbociclib, the median progression-free survival was 22.8 months for first-line treatment, ...

2. clinicaltrial.be clinicaltrial.be/en/details/3963?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

A Study of H3B-6545 in Combination With Palbociclib in Wo... The primary objective of this study is to evaluate the safety and tolerability of H3B-6545 and palbociclib when administered in combination ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT337059

Phase 1b study of H3B-6545 in combination with ... Phase 1b study of H3B-6545 in combination with palbociclib in women with metastatic estrogen receptor–positive (ER+), human epidermal growth factor receptor 2 ( ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04288089

A Study of H3B-6545 in Combination With Palbociclib in ... The primary objective of this study is to evaluate the safety and tolerability of H3B-6545 and palbociclib when administered in combination.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10854569/

Therapies for the Treatment of Advanced/Metastatic ... Data presented at the 2023 ESMO Breast Cancer Annual Congress showed a median follow up of 79.8 months, the median OS was 69.2 months, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36456385/

A Multinational, Pooled Analysis From the Ibrance Real ... The 12-month progression-free rate was 88% for palbociclib plus an AI and 79% for palbociclib plus fulvestrant; the 12-month survival rate was 96% in both ...