What is the mechanism of action of this treatment?

Targeted therapies for breast cancer, such as those aimed at the PIK3CA gene mutation, work by inhibiting specific molecular pathways that are essential for cancer cell growth and survival. For example, LOXO-783 and similar agents target the PI3K pathway, which is often mutated in breast cancer, leading to uncontrolled cell proliferation. By blocking this pathway, these treatments can effectively slow down or stop the growth of cancer cells. This approach is crucial for breast cancer patients as it offers a more personalized treatment option, potentially improving efficacy and reducing side effects compared to conventional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly targeted therapies like LOXO-783 for PIK3CA gene mutations, can cause side effects such as fatigue, nausea, diarrhea, liver toxicity, and skin rashes. Hormonal agents like tamoxifen may lead to hot flashes, vaginal dryness, and an increased risk of blood clots, while aromatase inhibitors can result in bone density loss, joint pain, and cardiovascular risks. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for breast cancer, particularly for those with PIK3CA gene mutations. One notable example is alpelisib (Piqray), which is used in combination with fulvestrant for the treatment of hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer. This approval highlights the focus on targeted therapies that inhibit the PI3K pathway, similar to the investigational drug LOXO-783 being studied for its safety, side effects, and effectiveness in treating breast cancer and other solid tumors with PIK3CA mutations.

What other types of research exist?

Promising alternatives to LOXO-783 for breast cancer patients with PIK3CA gene mutations include Alpelisib (a PI3K inhibitor) in combination with endocrine therapy, and Taselisib (another PI3K inhibitor). Both have shown efficacy in clinical trials for PIK3CA-mutated breast cancer. Additionally, novel therapies such as Capivasertib (an AKT inhibitor) and Ipatasertib (another AKT inhibitor) are being investigated and may offer potential benefits.

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Small Molecule Inhibitor

LOXO-783 for Breast Cancer (PIKASSO-01 Trial)

Phase 1

Waitlist Available

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

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

Must have

Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale

Have advanced breast cancer or another solid tumor with the presence of a phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) H1047R mutation (or other Sponsor and safety review committee (SRC)-approved, activating PIK3CA mutations other than H1047R mutation)

Must not have

Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or other clinically significant active disease process

Known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 36 months or 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing LOXO-783, a new drug, to see if it is safe and effective for patients with breast cancer and other solid tumors that have a change in the PIK3CA gene. The drug works by blocking a gene that helps cancer cells grow.

Who is the study for?

This trial is for adults with advanced breast cancer or other solid tumors that have a specific gene change (PIK3CA mutation). Participants can have had several prior treatments but must be recovered from their side effects. They need to have measurable disease, adequate organ function, and an ECOG performance status of 0 or 1. Women should be postmenopausal; men agree to hormone suppression.

What is being tested?

LOXO-783 is being tested for its safety and effectiveness in treating certain cancers. The study will explore how well it works on tumors with the PIK3CA gene mutation over a period of up to three years. Patients may also receive other standard cancer treatments like Fulvestrant or Abemaciclib as part of the study.

What are the potential side effects?

Possible side effects include typical reactions seen with cancer therapies such as fatigue, nausea, diarrhea, blood count changes, and potential risks associated with hormonal changes due to treatment. Specific side effects related to LOXO-783 are not listed but would be monitored closely.

Eligibility Criteria

Inclusion Criteria

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

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

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My advanced cancer has a specific PIK3CA mutation.

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I have an advanced solid tumor and have had up to 5 treatments for it.

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I have breast cancer with at least one bone lesion.

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I have a tumor outside the breast that can be measured.

Exclusion Criteria

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

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I do not have any active, uncontrolled infections or significant diseases.

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I have or might have untreated brain involvement.

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My endometrial cancer has specific genetic changes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 36 months or 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 36 months or 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 36 months or 3 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

Phase 1 a: To determine the MTD/RP2D of LOXO-783: Number of patients with DLT-equivalent toxicities

Phase 1 a: To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of LOXO-783: Number of patients with dose-limiting toxicities (DLTs)

Secondary study objectives

To assess the PK of LOXO-783: Maximum drug concentration (Cmax)

To assess the pharmacokinetics (PK) of LOXO-783: Area under the concentration versus time curve (AUC)

To evaluate the preliminary antitumor activity of LOXO-783: Best overall response (BOR)

+7 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

7Treatment groups

Experimental Treatment

Group I: Phase 1B: Part FExperimental Treatment2 Interventions

Multiple randomized dose levels of LOXO-783 orally with fulvestrant intramuscularly

Group II: Phase 1B: Part EExperimental Treatment1 Intervention

LOXO-783 orally

Group III: Phase 1B: Part DExperimental Treatment2 Interventions

LOXO-783 orally in combination with paclitaxel intravenously

Group IV: Phase 1B: Part CExperimental Treatment2 Interventions

LOXO-783 orally in combination with fulvestrant intramuscularly

Group V: Phase 1B: Part BExperimental Treatment5 Interventions

LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally

Group VI: Phase 1B: Part AExperimental Treatment4 Interventions

LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally

Group VII: Phase 1A: LOXO-783 Monotherapy Dose EscalationExperimental Treatment1 Intervention

LOXO-783 administered orally

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Fulvestrant

2011

Completed Phase 3

~3510

LOXO-783

2023

Completed Phase 1

~80

Imlunestrant

2022

Completed Phase 1

~170

Abemaciclib

2019

Completed Phase 2

~1890

Paclitaxel

2011

Completed Phase 4

~5370

0 / 8Eligibility 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

Targeted therapies for breast cancer, such as those aimed at the PIK3CA gene mutation, work by inhibiting specific molecular pathways that are essential for cancer cell growth and survival. For example, LOXO-783 and similar agents target the PI3K pathway, which is often mutated in breast cancer, leading to uncontrolled cell proliferation. By blocking this pathway, these treatments can effectively slow down or stop the growth of cancer cells. This approach is crucial for breast cancer patients as it offers a more personalized treatment option, potentially improving efficacy and reducing side effects compared to conventional chemotherapy.