PI3K-beta Inhibitor for PTEN Loss-Related Cancers

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antiplatelets, mTOR inhibitors

Disqualifiers: Hypersensitivity, Tumor mutations, 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: 5

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 complete loss of PTEN expression. GSK2636771 may block a protein called PI3K-beta, which may be needed for growth of cancer cells with complete loss of PTEN expression. 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 PTEN loss-related cancers?

Research shows that in PTEN-mutated tumors, blocking PI3Kβ can slow down cancer growth by affecting a key pathway (Akt/mTOR) involved in cell survival and growth. However, combining this with other inhibitors may be more effective in stopping tumor growth. ^{1 2 3 4 5}

What safety data exists for PI3K-beta inhibitors like GSK2636771 in humans?

A first-in-human study of a similar PI3K-beta inhibitor, SAR260301, was conducted to determine its safety and the maximum dose that can be tolerated in patients with advanced solid tumors. This study provides some safety data for PI3K-beta inhibitors in humans. ^{1 2 3 6 7}

How is the drug GSK2636771 unique for treating PTEN loss-related cancers?

GSK2636771 is unique because it specifically targets the PI3K-beta pathway, which is crucial in cancers with PTEN loss, unlike other treatments that may not focus on this specific pathway. This selectivity helps in minimizing side effects and improving effectiveness in PTEN-deficient tumors. ^{1 2 3 8 9}

Research Team

Filip Janku

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with various cancers, including solid tumors and blood-related cancers like lymphoma and multiple myeloma, that have lost PTEN expression. Participants must have normal heart rhythms and adequate hemoglobin levels. They can't join if they've had certain treatments targeting similar pathways or have lung disease, congenital platelet defects, or are on specific anti-platelet drugs.

Inclusion Criteria

My kidney function, measured by creatinine levels, is within the normal range.

My recent ECG showed no significant heart issues.

My cancer lacks PTEN as shown by a specific test.

Exclusion Criteria

I have never had interstitial lung disease or pneumonitis.

If I need anti-platelet therapy, it must be approved by the study's lead.

I don't have inherited platelet disorders and am not taking specific anti-platelet medications.

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

Visits every 2 cycles for the first 26 cycles, then every 3 cycles

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

Every 3 months for <= 2 years, then every 6 months for year 3

Treatment Details

Interventions

• GSK2636771

Trial Overview The study tests GSK2636771's effectiveness in shrinking or halting the growth of cancer cells lacking PTEN expression. This drug aims to block PI3K-beta protein which might be essential for the proliferation of these cancer cells.

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+

References

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

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

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

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

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

Activating Mutations in PIK3CB Confer Resistance to PI3K Inhibition and Define a Novel Oncogenic Role for p110β. [2021]

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

PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. [2022]

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

PIK3CA and PTEN gene and exon mutation-specific clinicopathologic and molecular associations in colorectal cancer. [2022]

6. 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]

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

Assessing PIK3CA and PTEN in early-phase trials with PI3K/AKT/mTOR inhibitors. [2022]

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

Discovery of a Phosphoinositide 3-Kinase (PI3K) β/δ Inhibitor for the Treatment of Phosphatase and Tensin Homolog (PTEN) Deficient Tumors: Building PI3Kβ Potency in a PI3Kδ-Selective Template by Targeting Nonconserved Asp856. [2019]

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

Concomitant Inhibition of PI3Kβ and BRAF or MEK in PTEN-Deficient/BRAF-Mutant Melanoma Treatment: Preclinical Assessment of SAR260301 Oral PI3Kβ-Selective Inhibitor. [2020]