What side effects are associated with this type of intervention?

Cyclin-dependent Kinase 4/6 (CDK4/6) inhibitors, commonly used in the treatment of breast cancer, are associated with several side effects. The most common include neutropenia (a decrease in white blood cells), fatigue, nausea, diarrhea, and alopecia (hair loss). Other potential side effects are infections due to lowered immunity, liver function abnormalities, and stomatitis (inflammation of the mouth). It is important for patients to 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 Cyclin-dependent Kinase 4/6 (CDK4/6) inhibitors for the treatment of breast cancer. These include palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio). These drugs are typically used in combination with hormone therapy for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. Palbociclib was the first CDK4/6 inhibitor approved by the FDA in 2015, followed by ribociclib in 2017, and abemaciclib in 2017. These treatments have shown to improve progression-free survival in patients with advanced breast cancer.

What other types of research exist?

Promising novel alternatives to PRT3645 for breast cancer patients include: 1) Abemaciclib, another CDK4/6 inhibitor with proven efficacy in HR-positive, HER2-negative breast cancer. 2) Ribociclib, also a CDK4/6 inhibitor, which has shown significant benefits in combination with endocrine therapy. 3) Alpelisib, a PI3K inhibitor, particularly for patients with PIK3CA-mutated breast cancer. 4) Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, approved for triple-negative breast cancer. These alternatives offer different mechanisms of action and have shown promising results in clinical trials.

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CDK4/6 Inhibitor

PRT3645 for Advanced Cancer

Phase 1

Waitlist Available

Research Sponsored by Prelude Therapeutics

Eligibility Criteria Checklist

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

Must have

Able to swallow and retain oral medication

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 or Karnofsky Performance Status (KPS) ≥80% (KPS is for GBM only)

Must not have

Clinically significant or uncontrolled cardiac disease, uncontrolled electrolyte disorders, uncontrolled or symptomatic CNS metastases or leptomeningeal disease except for GBM

Endometrial cancer patients who had received prior treatment with a CDK 4/6 inhibitor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline through approximately 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests PRT3645, a drug that blocks proteins helping cancer cells grow, in patients with advanced or spreading cancers not responding to other treatments. It aims to find the safest dose and see how well patients tolerate it.

Who is the study for?

This trial is for adults with certain advanced or metastatic solid tumors, including specific types of breast cancer, brain tumors, lung cancer, head and neck cancers, sarcoma, and endometrial cancer. Participants must have progressed beyond standard treatments or be ineligible for them. They should be in good physical condition (ECOG 0-1), able to provide a tumor tissue sample, comply with study procedures and have adequate organ function.

What is being tested?

PRT3645 is being tested in this Phase 1 trial. It's a new drug aimed at inhibiting CDK4/6 which are proteins involved in cell division. The study will gradually increase doses to find the highest dose patients can take without serious side effects (maximally tolerated dose) and decide on the best dose for future studies.

What are the potential side effects?

As PRT3645 is still under investigation, potential side effects include those commonly associated with CDK4/6 inhibitors such as nausea, diarrhea, low blood cell counts leading to increased infection risk or bleeding problems; fatigue; hair thinning; liver issues; mouth sores.

Eligibility Criteria

Inclusion Criteria

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

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I can swallow and keep down pills.

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I am fully active or able to carry out light work.

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My cancer has progressed or can't be treated with standard therapies.

Exclusion Criteria

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

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I do not have uncontrolled heart issues, electrolyte disorders, or severe brain/spinal cord disease.

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I have endometrial cancer and was treated with a CDK 4/6 inhibitor.

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My advanced cancer has spread widely and is causing symptoms.

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I am not taking medications that strongly affect liver enzymes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline through approximately 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline through approximately 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline through approximately 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Dose limiting toxicity (DLT) of PRT3645

Maximally tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT3645

Safety and tolerability of PRT3645: AEs, CTCAE Assessments

Secondary study objectives

Efficacy of PRT3645: Tumor assessment and responses

Pharmacodynamic effect of PRT3645: Target engagement

Pharmacokinetic profile of PRT3645: Minimum and maximum observed plasma concentration

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: PRT3645Experimental Treatment1 Intervention

PRT3645 capsules will be self-administered once daily, continuously, at the dose-level assigned

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

PRT3645

2022

Completed Phase 1

~30

0 / 7Eligibility 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

Cyclin-dependent Kinase 4/6 (CDK4/6) inhibitors, such as PRT3645, target proteins essential for cell cycle progression from the G1 to the S phase. By inhibiting CDK4/6, these drugs prevent phosphorylation of the retinoblastoma protein (Rb), thereby halting cell division and inducing cell cycle arrest. This mechanism is particularly significant for breast cancer patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) subtypes, as these cancers often rely on CDK4/6 for proliferation. By effectively stopping cancer cell growth, CDK4/6 inhibitors can improve progression-free survival and offer a targeted treatment option with potentially fewer side effects compared to traditional chemotherapy.

CDK4/6 Inhibitors in Combination With Hormone Therapy for HR+/HER2- Advanced Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.