PI3K-beta Inhibitor for Tumors

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: mTOR inhibitors, PI3K inhibitors

Disqualifiers: Hypersensitivity, Tumor aberrations, Lung disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: Up to 3 years

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II MATCH treatment trial identifies the effects of GSK2636771 in patients whose cancer has a genetic change called PTEN mutation or deletion. GSK2636771 may block a protein called PI3K-beta, which may be needed for growth of cancer cells that express PTEN mutations. Researchers hope to learn if GSK2636771 will shrink this type of cancer or stop its growth.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain cancer treatments targeting the PI3K beta, AKT, or mTOR pathways before. If you are on anti-platelet drugs like clopidogrel, you cannot participate.

What data supports the effectiveness of the drug GSK2636771 for tumors?

In a study, GSK2636771, a drug targeting a specific part of cancer cells, showed potential benefits for some patients with advanced solid tumors, especially those with certain genetic changes. One patient with prostate cancer had a partial response lasting over a year, and others experienced benefits for at least 24 weeks. ^{1 2 3 4 5}

What is the safety profile of the PI3K-beta inhibitor GSK2636771 in humans?

In a study with 65 patients having advanced solid tumors, GSK2636771 was generally safe at a dose of 400 mg once daily. Common side effects included diarrhea, nausea, and vomiting, while some patients experienced low phosphate and calcium levels in the blood. ^{1 2 4 5 6}

How is the drug GSK2636771 different from other treatments for tumors?

GSK2636771 is unique because it specifically targets the PI3K-beta enzyme, which is often active in certain tumors, especially those lacking the PTEN gene. This selectivity helps avoid the broader side effects seen with drugs that target multiple PI3K enzymes, making it potentially more effective and safer for patients with specific genetic tumor profiles. ^{1 2 4 5 7}

Research Team

Filip Janku

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for cancer patients with a specific genetic change called PTEN mutation or deletion. They must have some PTEN expression, normal hemoglobin levels, acceptable kidney function, and a stable heart rhythm on an ECG. Excluded are those allergic to GSK2636771, with certain other gene changes that affect cancer growth pathways, prior treatments targeting similar pathways, history of lung disease like pneumonitis, congenital platelet defects or current use of certain anti-platelet drugs.

Inclusion Criteria

My cancer does not show a complete loss of PTEN by IHC.

My kidney function, measured by creatinine levels or clearance, is within the required range.

My cancer shows PTEN protein presence.

Exclusion Criteria

I have not been treated with drugs targeting PI3K beta, AKT, or mTOR.

I am not allergic to GSK2636771 or similar drugs.

I have never had interstitial lung disease or pneumonitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PI3K-beta inhibitor GSK2636771 orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Tumor assessments at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months if less than 2 years from study entry, and then every 6 months for year 3.

Up to 3 years

Treatment Details

Interventions

• GSK2636771

Trial Overview The trial tests the drug GSK2636771 in cancers with PTEN mutations. This drug aims to block PI3K-beta protein which might be essential for the growth of these cancer cells. The goal is to see if this targeted treatment can shrink tumors or halt their progression.

Participant Groups

Group I: Treatment (GSK2636771) Experimental Treatment 1 Intervention

Patients receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase I study involving 170 patients with advanced solid tumors, GSK2126458 (GSK458) was found to have a maximum tolerated dose (MTD) of 2.5 mg once daily, with common side effects including diarrhea and skin rash.

The study showed that GSK458 led to durable objective responses in various cancer types, and interestingly, these responses were not dependent on PIK3CA mutations, suggesting that other factors may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I Study of GSK2126458, an Oral Pan-Class I Phosphatidylinositol-3-Kinase Inhibitor, in Patients with Advanced Solid Tumor Malignancies. Munster, P., Aggarwal, R., Hong, D., et al.[2021]

GSK2636771, a selective inhibitor of the PI3Kβ pathway, was found to have a manageable safety profile with dose-limiting toxicities including hypophosphatemia and hypocalcemia, and the recommended phase II dose was established at 400 mg once daily.

In a study of 65 patients with advanced solid tumors, particularly those with PIK3CB alterations, GSK2636771 showed promising antitumor activity, with some patients experiencing durable clinical benefits lasting over 24 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors. Mateo, J., Ganji, G., Lemech, C., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

First-in-human trial of the PI3Kβ-selective inhibitor SAR260301 in patients with advanced solid tumors. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I Study of GSK2126458, an Oral Pan-Class I Phosphatidylinositol-3-Kinase Inhibitor, in Patients with Advanced Solid Tumor Malignancies. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Feedback suppression of PI3Kα signaling in PTEN-mutated tumors is relieved by selective inhibition of PI3Kβ. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Biological characterization of SN32976, a selective inhibitor of PI3K and mTOR with preferential activity to PI3Kα, in comparison to established pan PI3K inhibitors. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

A First-Time-in-Human Study of GSK2636771, a Phosphoinositide 3 Kinase Beta-Selective Inhibitor, in Patients with Advanced Solid Tumors. [2022]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Present and future of PI3K pathway inhibition in cancer: perspectives and limitations. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Design, Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Selective PI3Kβ Inhibitors. [2020]