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PALAZESTRANT

PALAZESTRANT (also known as OP-1250) is an investigational drug currently being studied in multiple clinical trials for the treatment of estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. As a Complete Estrogen Receptor Antagonist (CERAN), PALAZESTRANT works by blocking the estrogen receptor, which can help slow or stop the growth of hormone-dependent breast cancer cells. The ongoing clinical trials are evaluating PALAZESTRANT both as a standalone treatment and in combination with other targeted therapies, comparing its effectiveness and safety against current standard treatments for patients with advanced or metastatic breast cancer.

Table of Contents

What is Palazestrant?

Palazestrant, also known as OP-1250, is a new medication being developed for the treatment of certain types of breast cancer. It is classified as a Complete Estrogen Receptor Antagonist (CERAN), which means it works by blocking the effects of estrogen on cancer cells[1]. This medication is currently being studied in clinical trials and is not yet approved for general use.

What Conditions Does Palazestrant Treat?

Palazestrant is designed specifically to treat breast cancer that is:

  • Estrogen Receptor-positive (ER+): This means the cancer cells have receptors that attach to the hormone estrogen, which helps them grow.
  • HER2-negative (HER2-): These cancer cells do not have large amounts of a protein called HER2 on their surface.
  • Locally advanced: Cancer that has spread from where it started to nearby tissue or lymph nodes.
  • Metastatic: Cancer that has spread to other parts of the body, such as the bones, liver, or lungs[2].

These types of breast cancer are often treated initially with hormone therapies, but sometimes the cancer stops responding to these treatments. Palazestrant is being studied as a potential option for patients whose cancer has progressed despite previous treatments[4].

How Does Palazestrant Work?

As a Complete Estrogen Receptor Antagonist, Palazestrant works by:

  • Binding to estrogen receptors on cancer cells
  • Blocking estrogen from attaching to these receptors
  • Preventing the cancer cells from receiving growth signals from estrogen
  • Potentially causing the cancer cells to stop growing or die[3]

Unlike some other hormone therapies, Palazestrant is designed to be a “complete” antagonist, meaning it may provide more thorough blocking of estrogen effects[1].

Combination Therapies

Researchers are studying Palazestrant both as a single medication and in combination with other cancer drugs. Some of the combinations being tested include:

Palazestrant with CDK4/6 Inhibitors

CDK4/6 inhibitors are medications that block certain proteins involved in cell division. Combinations being studied include:

  • Palazestrant + Ribociclib (Kisqali®): This combination is being evaluated for first-line treatment of ER+/HER2- advanced breast cancer[1].
  • Palazestrant + Palbociclib (Ibrance®): Another combination being studied for advanced or metastatic ER+/HER2- breast cancer[2].

Palazestrant with PI3K/mTOR Pathway Inhibitors

These medications target different growth pathways in cancer cells:

  • Palazestrant + Alpelisib (Piqray®): Alpelisib is a PI3K inhibitor that blocks a specific cellular pathway that can drive cancer growth[3].
  • Palazestrant + Everolimus: Everolimus is an mTOR inhibitor that affects another cellular pathway involved in cancer cell growth and survival[3].

Clinical Trials

Palazestrant is being evaluated in several clinical trials, including:

OPERA-01 Trial

This is a Phase 3 trial comparing Palazestrant to standard treatments (fulvestrant or aromatase inhibitors like anastrozole, letrozole, or exemestane) in patients whose cancer has progressed after receiving endocrine therapy combined with a CDK4/6 inhibitor[4].

OPERA-02 Trial

This Phase 3 trial is comparing the combination of Palazestrant with ribociclib versus letrozole with ribociclib for first-line treatment of ER+/HER2- advanced breast cancer. The study aims to enroll approximately 1,000 participants who have not received prior systemic anti-cancer treatment for advanced disease[1].

Phase 1 Combination Studies

Several Phase 1 studies are evaluating the safety and preliminary effectiveness of Palazestrant in combination with other medications, including palbociclib, ribociclib, alpelisib, and everolimus[2][3].

Dosage and Administration

Based on current clinical trials, Palazestrant is being tested at various doses, including:

  • 90 mg once daily[1]
  • 120 mg once daily[4]

The medication is taken orally (by mouth) on a continuous schedule, typically on a 4-week (28-day) cycle[1]. The optimal dose is still being determined through clinical trials.

Potential Benefits

While research is ongoing, Palazestrant may potentially offer several advantages:

  • It may be effective in patients whose cancer has become resistant to other hormone therapies
  • As an oral medication, it can be taken at home rather than requiring injections or infusions
  • It is being studied both as a single agent and in combination with other targeted therapies, potentially providing multiple treatment options
  • Early clinical trials are evaluating its effectiveness in patients with specific genetic mutations (such as ESR1 mutations) that can make cancer resistant to some standard treatments[4]

Since clinical trials are still in progress, the full safety profile and effectiveness of Palazestrant are not yet fully established. The outcomes of these trials will help determine if and when Palazestrant might become an approved treatment option for patients with ER+/HER2- advanced or metastatic breast cancer[1][4].

Trial Name Phase Treatment Arms Patient Population Primary Outcomes
OPERA-02 (NCT07085767) Phase 3 Palazestrant + Ribociclib vs. Letrozole + Ribociclib ER+/HER2- advanced breast cancer with no prior systemic anti-cancer treatment for advanced disease Progression-Free Survival (PFS)
Phase 1 OP-1250 with Palbociclib (NCT05266105) Phase 1 Palazestrant + Palbociclib HR+/HER2- advanced or metastatic breast cancer Dose Limiting Toxicities, Adverse Events, Plasma levels of OP-1250
Phase 1b Combination Study (NCT05508906) Phase 1b Three treatment groups: 1. Palazestrant + Ribociclib 2. Palazestrant + Alpelisib 3. Palazestrant + Everolimus Advanced and/or metastatic ER+/HER2- breast cancer Dose Limiting Toxicities, Adverse Events, Pharmacokinetics
OPERA-01 (NCT06016738) Phase 3 Palazestrant vs. Standard of Care (fulvestrant, anastrozole, letrozole, or exemestane) ER+/HER2- advanced or metastatic breast cancer following endocrine and CDK4/6 inhibitor therapy Safety measures in dose-selection part; Progression-Free Survival (PFS) in main trial

FAQ

  • What is PALAZESTRANT and how does it work? PALAZESTRANT (also known as OP-1250) is an investigational drug that functions as a Complete Estrogen Receptor Antagonist (CERAN). It works by blocking the estrogen receptor in breast cancer cells, which can help slow or stop the growth of hormone-dependent tumors. This mechanism is particularly important for treating estrogen receptor-positive (ER+) breast cancers, which rely on estrogen to grow and spread.
  • What types of breast cancer is PALAZESTRANT being studied for? PALAZESTRANT is specifically being studied for the treatment of estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. This type of breast cancer is hormone-dependent and represents a significant percentage of all breast cancer cases. The clinical trials are including both locally advanced breast cancer and metastatic breast cancer patients.
  • What other drugs is PALAZESTRANT being combined with in clinical trials? PALAZESTRANT is being studied in combination with several different targeted therapies. These include CDK4/6 inhibitors such as ribociclib (KISQALI®) and palbociclib (IBRANCE®), a PI3K inhibitor called alpelisib (PIQRAY®), and an mTOR inhibitor called everolimus. These combinations are being tested to determine if they provide better outcomes than current standard treatments for advanced breast cancer.
  • What are the main outcomes being measured in the PALAZESTRANT clinical trials? The main outcomes being measured include progression-free survival (PFS), which is the length of time patients live without their cancer getting worse; overall survival (OS), which is how long patients live after starting treatment; overall response rate (ORR), which measures how many patients' tumors shrink; and clinical benefit rate (CBR), which includes patients whose disease stabilizes for at least 24 weeks. Researchers are also carefully monitoring safety, side effects, and how the drug behaves in the body (pharmacokinetics).
  • Who can participate in the PALAZESTRANT clinical trials? The clinical trials are generally enrolling adult patients with ER+/HER2- advanced or metastatic breast cancer. Some trials are specifically for patients who have not received prior treatment for advanced disease, while others are for patients whose cancer has progressed after receiving standard treatments like endocrine therapy and CDK4/6 inhibitors. Each trial has specific eligibility criteria that determine who can participate based on their cancer history, prior treatments, and overall health status.

Ongoing Clinical Trials on PALAZESTRANT

  • A study of palazestrant and ribociclib compared to letrozole and ribociclib for patients with advanced ER+ HER2- breast cancer

    Recruiting

    1 1 1
    Investigated drugs:
    Austria Belgium Czechia France Germany Greece +7

  • Study of OP-1250 for Treating Advanced or Metastatic ER+, HER2- Breast Cancer in Patients After Endocrine and CDK4/6 Inhibitor Therapy

    Recruiting

    1 1 1 1
    Investigated drugs:
    Austria Belgium Bulgaria Czechia France Germany +7

Glossary

  • PALAZESTRANT (OP-1250): An investigational drug that acts as a Complete Estrogen Receptor Antagonist (CERAN), designed to block the estrogen receptor in breast cancer cells to slow or stop tumor growth.
  • ER+ (Estrogen Receptor-Positive): A type of breast cancer where the cancer cells have receptors for estrogen on their surface. These cancers can be stimulated to grow by estrogen and often respond to hormone therapy treatments.
  • HER2- (Human Epidermal Growth Factor Receptor 2-Negative): Refers to breast cancer cells that do not have an excess of the HER2 protein, which is involved in normal cell growth. HER2-negative cancers do not respond to therapies targeting HER2.
  • Advanced Breast Cancer: Breast cancer that has spread beyond the breast to nearby tissues and lymph nodes but not to distant parts of the body.
  • Metastatic Breast Cancer: Breast cancer that has spread from the original tumor site to distant organs or parts of the body, such as the bones, liver, lungs, or brain.
  • CERAN (Complete Estrogen Receptor Antagonist): A type of drug that fully blocks the action of estrogen on estrogen receptors, preventing estrogen from stimulating cancer cell growth.
  • CDK4/6 Inhibitor: A class of drugs that block certain proteins (cyclin-dependent kinases 4 and 6) involved in cell division, which can help slow cancer growth. Examples include ribociclib, palbociclib, and abemaciclib.
  • Ribociclib (KISQALI®): A CDK4/6 inhibitor used to treat advanced or metastatic breast cancer. It works by blocking proteins that help cancer cells divide and grow.
  • Palbociclib (IBRANCE®): A CDK4/6 inhibitor used in the treatment of hormone receptor-positive, HER2-negative advanced breast cancer.
  • Alpelisib (PIQRAY®): A PI3K inhibitor used to treat hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer.
  • Everolimus: An mTOR inhibitor used in the treatment of certain types of advanced breast cancer, working by blocking a protein that helps cancer cells grow and divide.
  • Fulvestrant: An estrogen receptor antagonist that both blocks and degrades estrogen receptors, used to treat hormone receptor-positive metastatic breast cancer.
  • Letrozole: An aromatase inhibitor that blocks the production of estrogen in the body, used to treat postmenopausal women with hormone receptor-positive breast cancer.
  • Aromatase Inhibitor: A class of drugs that block the enzyme aromatase, which is responsible for producing estrogen in the body. Examples include anastrozole, letrozole, and exemestane.
  • Progression-Free Survival (PFS): The length of time during and after treatment that a patient lives with cancer without the disease getting worse.
  • Overall Survival (OS): The length of time from either diagnosis or start of treatment that patients are still alive.
  • Overall Response Rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment.
  • Clinical Benefit Rate (CBR): The percentage of patients who achieve complete response, partial response, or stable disease with a duration of at least 24 weeks.
  • Duration of Response (DOR): The time from first documented response to disease progression.
  • Blinded Independent Review Committee (BIRC): A group of independent experts who review clinical trial data, such as imaging scans, without knowing which treatment a patient received, to provide an unbiased assessment of the treatment's effects.
  • Randomized Clinical Trial: A study in which participants are randomly assigned to different treatment groups, helping to reduce bias when comparing the effectiveness of treatments.
  • Double-Blind Study: A clinical trial design where neither the participants nor the researchers know which treatment a participant is receiving until the study is completed.
  • Phase 1 Clinical Trial: The first stage of clinical testing, primarily focused on evaluating a drug's safety, determining appropriate dosage, and identifying side effects.
  • Phase 3 Clinical Trial: A larger-scale clinical trial that compares the effectiveness and safety of a new treatment to the current standard treatment in a larger group of people.
  • ESR1 Mutation: A mutation in the estrogen receptor gene that can develop in breast cancer cells, often as a resistance mechanism to hormone therapy, potentially making the cancer less responsive to certain treatments.

References