H3B-6545 + Palbociclib for Breast Cancer

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

31 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination H3B-6545 and Palbociclib for breast cancer?

Palbociclib, a part of the treatment, has been shown to be effective in treating advanced breast cancer when combined with other drugs, significantly prolonging the time patients live without the cancer getting worse. In real-world studies, it has been well tolerated and effective, with high progression-free and survival rates. ^{1 2 3 4 5}

Is the combination of H3B-6545 and Palbociclib safe for humans?

Palbociclib (also known as Ibrance) has been shown to have a manageable safety profile in treating advanced breast cancer, with neutropenia (a low level of white blood cells) being the most common side effect. It is generally well-tolerated when combined with other cancer treatments, maintaining patients' quality of life. ^{1 4 6 7 8}

What makes the drug combination H3B-6545 and Palbociclib unique for breast cancer treatment?

The combination of H3B-6545 and Palbociclib is unique because Palbociclib is a selective inhibitor of cyclin-dependent kinases (CDK) 4 and 6, which are important for cell cycle progression, and it is used in hormone receptor-positive, HER2-negative advanced breast cancer. This combination may enhance the effectiveness of treatment by targeting specific pathways involved in cancer cell growth. ^{2 6 9 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. England 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. [2023]

2. France pubmed.ncbi.nlm.nih.gov

Impact of Dose Reduction on Efficacy: Implications of Exposure-Response Analysis of Palbociclib. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Palbociclib for Male Patients with Metastatic Breast Cancer. [2021]

4. France pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Real-world treatment of patients with palbociclib for HR+/HER2-advanced/metastatic breast cancer: the Europe IRIS study. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Palbociclib: first global approval. [2018]

7. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Real-World Treatment Patterns and Clinical Outcomes in Patients Receiving Palbociclib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced or Metastatic Breast Cancer in Argentina: The IRIS Study. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment patterns and clinical outcomes among patients receiving palbociclib in combination with an aromatase inhibitor or fulvestrant for HR+/HER2-negative advanced/metastatic breast cancer in real-world settings in the US: Results from the IRIS study. [2019]

10. China pubmed.ncbi.nlm.nih.gov

Ki67 and progesterone receptor status predicts sensitivity to palbociclib: a real-world study. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer. [2023]