What side effects are associated with this type of intervention?

Common treatments for breast cancer, including anti-cancer agents like fulvestrant, letrozole, palbociclib, and tamoxifen, have various side effects. Fulvestrant can cause injection site pain, nausea, and fatigue. Letrozole, an aromatase inhibitor, may lead to bone density loss, joint pain, and cardiovascular risks. Palbociclib, a CDK4/6 inhibitor, is associated with neutropenia, fatigue, and gastrointestinal issues. Tamoxifen can cause hot flashes, increased risk of thromboembolic events, and endometrial cancer. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for hormone receptor-positive breast cancer, which are similar to the ones being studied in the trial PF-07248144. Fulvestrant, an estrogen receptor antagonist, is approved for use in postmenopausal women with hormone receptor-positive metastatic breast cancer. Letrozole, an aromatase inhibitor, is approved for the adjuvant treatment of hormone receptor-positive early breast cancer and for first-line treatment of postmenopausal women with hormone receptor-positive or unknown advanced breast cancer. Palbociclib, a CDK4/6 inhibitor, is approved for use in combination with letrozole or fulvestrant for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. These treatments target the hormonal pathways and cell cycle regulation, similar to the investigational agent PF-07248144.

What other types of research exist?

Promising novel alternatives to PF-07248144 for breast cancer patients include the combination of fulvestrant plus everolimus, which has been shown to be safe and effective for hormone-receptor positive, HER2-negative disease. Additionally, the pan-PI3K inhibitor buparlisib in combination with fulvestrant has shown activity. These alternatives are based on recent clinical trial data and could be considered for treatment in 2024.

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Monoclonal Antibodies

PF-07248144 for Breast Cancer (KAT6 Trial)

Phase 1

Recruiting

Research Sponsored by Pfizer

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Female or male patients aged ≥ 18 years (Japan ≥ 20 years) (South Korea ≥ 19 years)

Participants with ER+HER2- breast cancer who have progressed after at least 1 prior line of treatment with an endocrine therapy and CDK4/6 inhibitor in the advanced or metastatic setting

Must not have

Unmanageable ascites

Major surgery, radiation therapy, or systemic anti-cancer therapy within 3 weeks prior to study entry

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new cancer drug called PF-07248144. It aims to find the best dose and see if it works better alone or with other cancer drugs. The study focuses on cancer patients who may not be responding well to current treatments.

Who is the study for?

Adults with advanced or metastatic ER+HER2- breast cancer, CRPC, or NSCLC who've exhausted standard treatments. Women must be non-childbearing or agree to induced menopause. Participants need at least one measurable lesion and good organ function but can't join if they have certain GI conditions, recent major surgery, other active cancers (except some skin cancers), are pregnant/breastfeeding, had extensive radiation to the bone marrow, ECG issues, or severe allergies to trial drugs.

What is being tested?

The study is testing PF-07248144's safety and effectiveness alone and in combination with fulvestrant; letrozole + palbociclib; or PF-07220060 + fulvestrant for treating certain advanced cancers. It's an open-label trial where everyone knows what treatment they're getting and aims to understand how the body processes these drugs.

What are the potential side effects?

Possible side effects include typical reactions related to hormone therapies like hot flashes and joint pain from letrozole/fulvestrant. Palbociclib may cause low blood cell counts leading to infection risk. Side effects of PF-07248144 aren't fully known yet but could involve digestive issues based on its exclusion criteria.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am at least 18 years old, or 20 if in Japan, or 19 if in South Korea.

Select...

My ER+HER2- breast cancer has worsened after treatment with endocrine therapy and CDK4/6 inhibitor.

Select...

I have a tumor that can be measured and hasn't been treated with radiation.

Select...

I am a woman with advanced breast cancer and I am not able to have children because I am postmenopausal.

Select...

My breast cancer is ER+HER2- and has worsened after treatment with a CDK4/6 inhibitor and hormone therapy.

Select...

I am willing to undergo treatment to stop my periods as part of my breast cancer treatment.

Select...

My ER+HER2- breast cancer has worsened despite treatment with CDK4/6 inhibitors and hormone therapy.

Select...

My breast cancer is ER+ and HER2-.

Select...

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have severe fluid buildup in my abdomen that can't be controlled.

Select...

I have not had major surgery, radiation, or cancer treatment in the last 3 weeks.

Select...

More than a quarter of my bone marrow has been exposed to radiation.

Select...

I am on blood thinners for treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Upper arm

Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms.

Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Expansion Arms

+2 more

Secondary study objectives

AUC from time zero to time of last measurable concentration (AUClast) in the participants in the food effect subset in monotherapy dose expansion arm

Amount of PF-07248144 excreted in urine relative to dose administered (%) in a sub-set of participants in monotherapy dose expansion arm.

Maximum Observed Concentration (Cmax) in the participants in the food effect subset in monotherapy dose expansion arm

+14 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

8Treatment groups

Experimental Treatment

Group I: China Monotherapy Dose ExpansionExperimental Treatment1 Intervention

PF-07248144 Monotherapy Dose Expansion

Group II: 2D Combination Dose Expansion ArmExperimental Treatment3 Interventions

PF-07248144 with PF-07220060 +Fulvestrant Dose Expansion

Group III: 2B Combination Dose Expansion ArmExperimental Treatment2 Interventions

PF-07248144 with Fulvestrant Dose Expansion

Group IV: 2A Monotherapy Dose Expansion ArmExperimental Treatment1 Intervention

PF-07248144 Monotherapy Dose Expansion

Group V: 1D Combination Dose EscalationExperimental Treatment3 Interventions

PF-07248144 with PF-07220060 +Fulvestrant

Group VI: 1C Combination Dose EscalationExperimental Treatment3 Interventions

PF-07248144 with Letrozole + Palbociclib Combination Dose Escalation

Group VII: 1B Combination Dose EscalationExperimental Treatment2 Interventions

PF-07248144 with Fulvestrant Combination Dose Escalation

Group VIII: 1A Monotherapy Dose EscalationExperimental Treatment1 Intervention

PF-07248144 Monotherapy Escalation

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Letrozole

2002

Completed Phase 4

~3590

Fulvestrant

2011

Completed Phase 3

~3510

Palbociclib

2017

Completed Phase 3

~3790

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for breast cancer include targeted therapies, hormone therapies, and chemotherapy. CDK4/6 inhibitors, such as palbociclib, work by blocking proteins that promote cell division, thereby slowing cancer growth. HER2-directed treatments like trastuzumab target the HER2 protein on cancer cells, inhibiting their growth and survival. Hormone therapies, including letrozole and fulvestrant, block or lower estrogen levels, which can fuel certain types of breast cancer. These mechanisms are crucial for breast cancer patients as they offer personalized treatment options that can improve outcomes and reduce side effects compared to traditional chemotherapy.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Challenges in the diagnosis and management of cervical neuroendocrine carcinoma.New drugs for breast cancer.