PF-07220060 + PF-07104091 for Breast Cancer

Not currently recruiting at 52 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pfizer

Must not be taking: CDK4/6 inhibitors, SERDs, Everolimus, PPIs

Disqualifiers: Active malignancy, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of two study medicines, PF-07220060 (Atirmociclib) and PF-07104091, for individuals with breast cancer or other solid tumors. It consists of two parts: the first part experiments with different doses, while the second part explores various combinations of the medicines. The goal is to determine the highest safe dose and assess the effectiveness of these medicines in treating breast cancer. Suitable candidates include those with breast cancer who have undergone prior treatments and those with other solid tumors lacking current treatment options. Participants will take the medications orally, undergo x-ray imaging, and be monitored for about two years. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude participants using certain drugs that affect heart rhythm or specific enzymes. It's best to discuss your current medications with the trial team to see if they might be an issue.

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

Research has shown that the drugs PF-07220060 and PF-07104091 have been tested for safety in patients with advanced or spreading solid tumors. These drugs target specific proteins (CDK4 and CDK2) that aid cancer cell growth. Early results suggest that most patients tolerate the treatment well.

In previous studies, patients experienced some side effects, which is common with cancer treatments. These included nausea, tiredness, and low blood cell counts. However, most side effects were manageable and did not require stopping the treatment.

Since this clinical trial is in its early stages, it primarily focuses on checking safety and determining the right dose. While there is some evidence of safety, more information is needed to understand all possible risks. As with any treatment, discussing personal health concerns with a doctor before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PF-07220060 and PF-07104091 for breast cancer because they offer a new approach by combining targeted therapies. Unlike traditional treatments like chemotherapy, which can affect both cancerous and healthy cells, this combination targets specific proteins involved in cancer cell growth. PF-07220060 and PF-07104091 work together to disrupt pathways that breast cancer cells rely on for survival, potentially leading to more effective and less harmful treatment. Additionally, some trial arms explore combining these drugs with fulvestrant or letrozole, which are standard hormone therapies, aiming to enhance their effectiveness against certain types of breast cancer. This innovative strategy could provide new hope for better outcomes in patients who have limited options with existing treatments.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that PF-07220060 and PF-07104091, studied together in this trial, are promising treatments for breast cancer. Early findings suggest that PF-07220060 targets a protein called CDK4, which aids cancer cell growth, while PF-07104091 targets CDK2, another protein involved in cancer cell growth. In this trial, these drugs are combined in various treatment arms to halt cancer progression by interfering with these proteins. Although researchers are still studying these treatments, early results offer hope for their effectiveness in treating breast cancer. As more information becomes available, a clearer understanding of their potential benefits will emerge. ^{1 2 3 4 6}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for people with certain types of breast cancer (HR+, HER2- or refractory HR+/HER2+) and those with solid tumors without standard treatment options. Participants must have tried at least one prior therapy, have a measurable lesion, and be in good physical condition (ECOG 0 or 1). They should not have received some specific treatments for advanced disease and must not need certain drugs that affect the study medication.

Inclusion Criteria

My breast cancer is resistant to hormone therapy and is HER2 positive.

I have had hormone therapy for my advanced cancer and it has progressed.

My kidney, liver, and bone marrow are functioning well.

Exclusion Criteria

Other protocol specific exclusion criteria may apply

I do not have any active, uncontrolled infections or illnesses related to HIV/AIDS, HBV, or HCV.

I have blood clotting issues but am on low-dose blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive increasing doses of PF-07220060 with PF-07104091 to determine the highest safe dose

28 days per cycle

Multiple visits per cycle

Dose Expansion

Participants receive one of two study medicine combinations to evaluate safety and effectiveness

Approximately 2 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PF-07104091
• PF-07220060

Trial Overview The trial tests PF-07220060 combined with PF-07104091, taken orally, to determine safety and effectiveness against breast cancer. It has two parts: dose escalation to find the highest safe doses, followed by dose expansion where participants receive set combinations. The goal is to compare experiences across different dosages over approximately two years.

How Is the Trial Designed?

Group I: Part 2C Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 + Letrozole (ER+/HER2- Breast Cancer with no prior treatment with any CDK4/6 inhibitor for advanced disease)

Group II: Part 2B Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 + Fulvestrant (ER+/HER2- Breast Cancer with at least 1 prior endocrine therapy and up to 1 prior line of chemotherapy for advanced or metastatic disease and no prior treatment with any CDK4/6 inhibitor for advanced disease)

Group III: Part 2A Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 + Fulvestrant (ER+/HER2- Breast Cancer with at least 1 prior systemic therapy for advanced or metastatic disease, including CDK4/6 inhibitor treatment and Endocrine Therapy)

Group IV: Part 1 Dose Escalation - Dose Level 8 Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)

Group V: Part 1 Dose Escalation - Dose Level 7 Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)

Group VI: Part 1 Dose Escalation - Dose Level 6 Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)

Group VII: Part 1 Dose Escalation - Dose Level 5 Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)

Group VIII: Part 1 Dose Escalation - Dose Level 4 Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)

Group IX: Part 1 Dose Escalation - Dose Level 3 Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)

Group X: Part 1 Dose Escalation - Dose Level 2 Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)

Group XI: Part 1 Dose Escalation - Dose Level 1 Experimental Treatment 1 Intervention

PF-07220060 + PF-07104091 dose escalation (Breast Cancer or solid tumors)

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a real-world study of 191 women with hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer, the combination of palbociclib and endocrine therapy showed a clinical benefit rate of 59.8%, with a median progression-free survival (PFS) of 13 months.

The treatment was more effective when given as a first-line therapy, resulting in a median PFS of 14 months, compared to shorter PFS durations in later treatment lines, indicating that earlier intervention may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study. Palumbo, R., Torrisi, R., Sottotetti, F., et al.[2022]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05262400

NCT05262400 | A Study to Learn About the ... The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called PF-07220060 and PF-07104091) in people with breast ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02204-X/fulltext

metastatic breast cancer and advanced solid tumors We present dose escalation multicenter data of PF-07220060 (PF-60, CDK4-selective inhibitor) plus PF-07104091 (PF-91, CDK2-selective inhibitor) in patients (pts) ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3010

First-in-human phase 1/2a study of a potent and novel ... PF-07104091 is a novel CDK2-selective inhibitor under investigation in pts with selected advanced or metastatic solid tumors.

4. pfizeroncologydevelopment.com pfizeroncologydevelopment.com/clinical_trial/nct05262400

Tegtociclib (PF-07104091) Atirmociclib | PF-07220060 is an investigational compound. Its safety and efficacy have not been established. A PHASE 1B/2, OPEN-LABEL, MULTICENTER, DOSE ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12477701/

Targeting CDK2 for cancer therapy - PMC Study PF-07220060 in Combination With PF-07104091 in Participants With Breast Cancer and Solid Tumors (NCT05262400), phase 1/2 study for advanced/metastatic ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1040842824000672

Cyclin-dependent kinase 2 (CDK2) inhibitors and others ... A similar safety profile was reported in monotherapy for the other advanced solid tumors. In evaluable mBC cases, the combination of PF-07220060 with ET has ...