Zanidatamab + Palbociclib + Fulvestrant for Breast Cancer

Recruiting at 13 trial locations

Overseen By Zymeworks Clinical Trial Resource

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Zymeworks Inc.

Must not be taking: CDK4/6 inhibitors

Disqualifiers: Cardiac disease, Hepatitis, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

51 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial requires that you stop any prior treatment with trastuzumab, pertuzumab, lapatinib, T-DM1, or other anti-HER2-targeted therapy, as well as chemotherapy, other anti-cancer therapy, or hormonal cancer therapy at least 3 weeks before starting the study treatment. If you are currently on these medications, you will need to stop them before joining the trial.

What data supports the effectiveness of the drug combination Zanidatamab, Palbociclib, and Fulvestrant for breast cancer?

Research shows that the combination of Palbociclib and Fulvestrant significantly improves the time patients live without their cancer getting worse in hormone receptor-positive, HER2-negative advanced breast cancer. This suggests that adding Zanidatamab might further enhance treatment effectiveness. ^{1 2 3 4 5}

Is the combination of Zanidatamab, Palbociclib, and Fulvestrant safe for humans?

Palbociclib and Fulvestrant have been used together in treating certain types of breast cancer and are generally well-tolerated, though they can cause side effects like low white blood cell counts, fatigue, and nausea. Zanidatamab's safety profile is not detailed here, but the combination of Palbociclib and Fulvestrant has been studied and approved for use in specific breast cancer cases. ^{1 2 5 6 7}

What makes the drug combination of Zanidatamab, Palbociclib, and Fulvestrant unique for breast cancer treatment?

This drug combination is unique because it combines Zanidatamab, a novel antibody targeting HER2, with Palbociclib and Fulvestrant, which are already used together to treat hormone receptor-positive, HER2-negative breast cancer. This combination aims to enhance treatment effectiveness by targeting both hormone receptors and HER2, potentially offering a new option for patients with this type of breast cancer. ^{1 2 3 5 8}

What is the purpose of this trial?

This is a multicenter, Phase 2a, open-label, 2-part study to investigate the safety, tolerability, and anti-tumor activity of ZW25 (zanidatamab) in combination with palbociclib plus fulvestrant. Eligible patients include those with locally advanced (unresectable) and/or metastatic human epidermal growth factor receptor 2 (HER2)-positive, hormone receptor (HR)-positive breast cancer.

Research Team

Elaina Gartner, MD

Principal Investigator

Zymeworks Inc.

Eligibility Criteria

This trial is for adults with advanced breast cancer that's both HER2-positive and hormone receptor-positive. They must have tried certain other treatments like trastuzumab without success, be in good physical condition (ECOG score of 0 or 1), and have no serious heart, lung, liver, or nervous system problems. People with active hepatitis B/C, HIV not well-controlled, recent heart attacks or unstable angina are excluded.

Inclusion Criteria

I've had specific treatments for my cancer and it has gotten worse despite them.

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

My heart pumps blood well, meeting the normal standards.

Exclusion Criteria

I have severe lung inflammation or scarring not caused by cancer spread.

I do not have severe nerve damage in my hands or feet.

I haven't taken any HER2-targeted cancer treatments in the last 3 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Part 1

Evaluation of safety and tolerability of ZW25 in combination with palbociclib plus fulvestrant to confirm recommended doses

4 weeks

Cycle 1 Day 1 to Day 28

Treatment - Part 2

Evaluation of anti-tumor activity of ZW25 with palbociclib plus fulvestrant at recommended dose levels

Up to approximately 2 years 10 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after last study dose

Treatment Details

Interventions

• Fulvestrant
• Palbociclib
• ZW25 (Zanidatamab)

Trial Overview The study tests ZW25 (zanidatamab) combined with palbociclib plus fulvestrant to see how safe it is and how well it works against this type of breast cancer. It's an open-label Phase 2a trial where everyone knows what treatment they're getting.

Participant Groups

Group I: ZW25 (zanidatamab) + palbociclib + fulvestrant Experimental Treatment 3 Interventions

ZW25 (zanidatamab) plus palbociclib, fulvestrant

Fulvestrant is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in United States as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Canada as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Approved in Japan as Faslodex for:

• Hormone receptor-positive metastatic breast cancer
• Locally advanced breast cancer

Who Is Running the Clinical Trial?

Zymeworks Inc.

Lead Sponsor

Trials

11

Recruited

2,400+

Jazz Pharmaceuticals

Lead Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

In the FLIPPER trial, the combination of palbociclib and fulvestrant significantly improved progression-free survival (PFS) in postmenopausal women with HR+/HER2- advanced breast cancer compared to placebo and fulvestrant.

Patient-reported outcomes indicated that while global health status and quality of life (QoL) were maintained during treatment with palbociclib/fulvestrant, the time to deterioration in QoL was longer with placebo/fulvestrant, suggesting that palbociclib/fulvestrant is a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. Tibau, A., Martínez, MT., Ramos, M., et al.[2023]

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]

In a phase II study involving 190 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of palbociclib and fulvestrant significantly improved one-year progression-free survival (PFS-1y) rates (83.5% vs. 71.9% for placebo) and median PFS (31.8 months vs. 22.0 months).

While the palbociclib/fulvestrant combination showed better efficacy, it was associated with higher rates of grade 3-4 adverse events, particularly neutropenia (68.1% vs. 0% in the placebo group), indicating a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Albanell, J., Martínez, MT., Ramos, M., et al.[2022]

In the PALOMA-3 study involving 521 patients with hormone receptor-positive, HER2- metastatic breast cancer, the combination of palbociclib and fulvestrant significantly improved global quality of life (QoL) scores compared to fulvestrant plus placebo, indicating better patient-reported outcomes.

Patients receiving palbociclib plus fulvestrant also experienced a significant reduction in pain and a delay in deterioration of both global QoL and pain compared to those on fulvestrant alone, highlighting the efficacy of this combination therapy in managing symptoms and improving quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial. Harbeck, N., Iyer, S., Turner, N., et al.[2022]

Palbociclib, when combined with fulvestrant, significantly improves progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer, showing a median PFS of 9.5 months compared to 4.6 months with placebo, based on a study of 521 women.

The safety profile of palbociclib includes common adverse reactions such as neutropenia and infections, which were observed in over 20% of patients, confirming its known side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Walker, AJ., Wedam, S., Amiri-Kordestani, L., et al.[2022]

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 521 premenopausal and postmenopausal patients with endocrine-resistant metastatic breast cancer, those treated with palbociclib and fulvestrant showed a higher rate of prolonged benefit (29%) compared to those on placebo and fulvestrant (15%).

Long-term responders to palbociclib-fulvestrant tended to have less disease burden at baseline and lower rates of certain mutations, but no specific molecular or clinical factors were identified as predictors of long-term benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. Cristofanilli, M., DeMichele, A., Giorgetti, C., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. [2023]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). [2022]

4. England pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial. [2022]

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

FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer. [2022]

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

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

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

Cediranib in combination with fulvestrant in hormone-sensitive metastatic breast cancer: a randomized Phase II study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in PALOMA-3. [2022]