What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving PIK3CA inhibitors like Inavolisib, often include side effects such as hyperglycemia, diarrhea, rash, and nausea. When combined with other therapies like endocrine treatments (e.g., letrozole, fulvestrant) and targeted therapies (e.g., trastuzumab, pertuzumab), additional side effects may include fatigue, neutropenia, anemia, and thrombocytopenia. These side effects can vary in severity and frequency, and it is important for patients to discuss potential risks and management strategies with their healthcare provider.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer targeting the PIK3CA mutation and related pathways. Alpelisib (Piqray) is a notable PIK3CA inhibitor approved for use in combination with fulvestrant for HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer. Other related treatments include everolimus (Afinitor), an mTOR inhibitor, used in combination with exemestane for HR-positive, HER2-negative advanced breast cancer after failure of treatment with letrozole or anastrozole. These approvals highlight the ongoing efforts to target specific genetic mutations and pathways in breast cancer treatment.

What other types of research exist?

Promising novel alternatives to Inavolisib for breast cancer patients include: 1) CDK4/6 inhibitors such as Abemaciclib, which has shown efficacy in combination with endocrine therapy. 2) Immune checkpoint inhibitors like Pembrolizumab, especially for patients with high PD-L1 expression. 3) PARP inhibitors such as Olaparib for patients with BRCA mutations. 4) Antibody-drug conjugates like Trastuzumab Deruxtecan for HER2-positive breast cancer. These alternatives have demonstrated significant clinical activity and are being actively studied in various clinical trials.

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PI3K Inhibitor

Inavolisib for Solid Cancers and Breast Cancer

Phase 1

Waitlist Available

Research Sponsored by Genentech, Inc.

Eligibility Criteria Checklist

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

Must have

Female participants with locally advanced or metastatic PIK3CA-mutant HER2+ breast cancer (Stage II Arm G)

All participants must provide tumor tissue from the primary or metastatic tumor site obtained from a prior or new biopsy or surgical procedure for detection of PIK3CA mutation by central laboratory test (Stages I and II)

Must not have

Known and untreated, or active central nervous system metastases

Congenital long QT syndrome, prolonged QT interval, or family history of sudden unexplained death or long QT syndrome

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests inavolisib, an oral drug, in patients with advanced or metastatic PIK3CA-mutant solid tumors, including breast cancer. The drug works by blocking a protein that helps cancer cells grow.

Who is the study for?

This trial is for adults with advanced or metastatic solid tumors, including breast cancer, that have a specific mutation (PIK3CA). Participants must be in good physical condition (ECOG 0 or 1) and expected to live at least 12 weeks. Women with hormone receptor-positive/HER2-negative or HER2-positive breast cancer are eligible. Key exclusions include recent other cancers, significant heart conditions, uncontrolled illnesses, prior treatments with certain drugs, and inability to swallow pills.

What is being tested?

The study tests the drug Inavolisib alone or combined with standard therapies for advanced breast cancer. It's an open-label Phase I trial with two stages: dose-escalation to find safe amounts of Inavolisib and expansion to see how well it works across seven different treatment combinations involving drugs like Palbociclib, Letrozole, Fulvestrant, Metformin, Trastuzumab and Pertuzumab.

What are the potential side effects?

Possible side effects may include digestive issues; changes in blood counts affecting liver and kidney function; fatigue; reactions related to the heart such as irregular heartbeat; potential interactions leading to increased risk of infection due to immune system effects; skin reactions; and symptoms from nervous system involvement.

Eligibility Criteria

Inclusion Criteria

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

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I am a woman with advanced breast cancer that is HER2 positive and has a PIK3CA mutation.

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I can provide a tissue sample from my cancer for testing.

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My cancer is advanced, cannot be cured, and has a PIK3CA mutation.

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

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My heart pumps blood well (ejection fraction is 50% or more).

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I am a woman with advanced breast cancer that is hormone receptor positive and HER2 negative.

Exclusion Criteria

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

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I have untreated brain metastases.

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I have a long QT syndrome or a family history of sudden death related to it.

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My breast cancer is of a rare type called metaplastic.

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I have had cancer spread to the lining of my brain and spinal cord.

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I do not have any serious infections needing IV antibiotics.

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I have received more than 360 mg/m2 of doxorubicin.

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I do not have uncontrolled high blood pressure or unstable chest pain.

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I have or had heart rhythm problems or heart failure needing medication.

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I have uncontrolled fluid buildup in my chest or abdomen.

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I take medication to manage my Type 1 or Type 2 diabetes.

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I do not have conditions that affect how my body absorbs food.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

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

Trial Design

9Treatment groups

Experimental Treatment

Group I: Stage II Arm G: Inavolisib + Trastuzumab + PertuzumabExperimental Treatment3 Interventions

Participants will receive inavolisib in combination with trastuzumab and pertuzumab (Days 1-21). Dose of inavolisib will be determined from the results of Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group II: Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + MetforminExperimental Treatment4 Interventions

Participants will receive inavolisib (Days 1-28) in combination with palbociclib (Days 1-21), fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles) and metformin (Days 1-28)(Cycle = 28 days). Dose of inavolisib will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group III: Stage II Arm E: Inavolisib + Palbociclib + FulvestrantExperimental Treatment3 Interventions

Participants will receive inavolisib (Days 1-28) in combination with palbociclib (Days 1-21) and fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles)(Cycle = 28 days). Dose of inavolisib will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group IV: Stage II Arm D: Inavolisib + FulvestrantExperimental Treatment2 Interventions

Participants will receive inavolisib on Days 1-28 in combination with fulvestrant on Day 1 and 15 of Cycle 1 and then on Day 1 from Cycle 2 (cycle length: 28 days). Dose of inavolisib will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group V: Stage II Arm C: Inavolisib + LetrozoleExperimental Treatment2 Interventions

Participants will receive inavolisib in combination with letrozole on Days 1-28 of each 28-day cycle. Dose of inavolisib will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group VI: Stage II Arm B: Inavolisib + Palbociclib + LetrozoleExperimental Treatment3 Interventions

Participants will receive inavolisib on Days 1-28 in combination with palbociclib on Days 1-21 and letrozole on Days 1-28 of each 28-day cycle. Dose of inavolisib will be decided based on the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group VII: Stage I Arm C: Inavolisib + LetrozoleExperimental Treatment2 Interventions

Participants will receive inavolisib in escalating dose levels along with letrozole on Days 1-28 of each 28-day cycle. The starting dose of inavolisib will not exceed the starting dose in Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group VIII: Stage I Arm B: Inavolisib + Palbociclib + LetrozoleExperimental Treatment3 Interventions

Participants will receive inavolisib in escalating dose levels (starting dose 3 mg) on Days 1-28, palbociclib on Days 1-21, and letrozole on Days 1-28 of each 28-day cycle. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group IX: Stage I Arm A: Inavolisib Single AgentExperimental Treatment1 Intervention

Participants will receive inavolisib in escalating dose levels with starting dose of 6 milligrams (mg). Participants will receive single dose of inavolisib on Day 1 of Cycle 1 followed by once daily from Day 8 of Cycle 1. (Cycle length: 35 days for Cycle 1 and 28 days for all other cycles). Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Inavolisib

2021

Completed Phase 2

~260

Metformin

2006

Completed Phase 4

~2430

Letrozole

2002

Completed Phase 4

~3590

Fulvestrant

2011

Completed Phase 3

~3520

Pertuzumab

2014

Completed Phase 3

~7500

Palbociclib

2017

Completed Phase 3

~3880

Trastuzumab

2014

Completed Phase 4

~5190

0 / 17Eligibility 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, such as PIK3CA inhibitors, HER2 inhibitors, and CDK4/6 inhibitors, work by targeting specific molecular pathways that are altered in cancer cells. PIK3CA inhibitors block the PI3K/AKT/mTOR pathway, reducing tumor growth and proliferation. HER2 inhibitors target the HER2 protein, which is overexpressed in some breast cancers, while CDK4/6 inhibitors interfere with cell cycle progression. These targeted therapies are important for breast cancer patients as they provide more personalized and effective treatment options with potentially fewer side effects compared to traditional chemotherapy.

Promising novel therapies for the treatment of endometrial cancer.New drugs for breast cancer.Highlights from the 42nd annual meeting of the American Society of Clinical Oncology Atlanta, GA, USA, 2-6 June 2006.