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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called GSK2636771, a PI3K-beta inhibitor, for certain types of cancer where the PTEN protein is missing. PTEN loss can lead to cancer growth, and this drug aims to block a protein called PI3K-beta, potentially stopping cancer cells from growing. The trial seeks to determine if this treatment can shrink the cancer or halt its growth. It may suit patients whose cancer lacks the PTEN protein and who haven't used similar treatments targeting the same pathways. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that GSK2636771 is likely to be safe for humans?

Research has shown that the treatment GSK2636771 was safe in earlier studies. In one study, researchers combined GSK2636771 with another drug, and this combination proved to be safe and well-tolerated. Patients in this study did not experience severe side effects, suggesting that GSK2636771 alone might also be manageable.

In another study, 32% of patients maintained stable disease with GSK2636771, meaning their cancer did not worsen. This supports its potential benefits along with its safety. Overall, these early findings suggest that GSK2636771 is reasonably safe, though further research is needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for PTEN loss-related cancers, which often include chemotherapy or hormone therapy, GSK2636771 is a PI3K-beta inhibitor that specifically targets a pathway frequently altered in these cancers. This drug blocks the PI3K-beta enzyme, which plays a key role in cell growth and survival, making it particularly promising for patients with PTEN loss, a common genetic alteration in several cancers. Researchers are excited because this targeted approach could potentially offer a more effective treatment with fewer side effects compared to conventional therapies.

What evidence suggests that GSK2636771 might be an effective treatment for PTEN loss-related cancers?

Research has shown that GSK2636771, the investigational treatment in this trial, has potential in treating cancers where the PTEN gene is completely lost. In a study of patients with this genetic change, 22% had stable disease, meaning their cancer did not grow for a period of time. Some patients experienced stable disease for six months or more. This treatment blocks the PI3K-beta protein, which aids cancer cell growth when PTEN is missing. Early studies also found that it can improve survival and increase immune cells in tumors. These findings suggest GSK2636771 might help slow or stop cancer growth in patients with PTEN loss. ^{4 6 7 8 9}

Who Is on the Research Team?

Filip Janku

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Treatment (GSK2636771) Experimental Treatment 1 Intervention

Patients receive PI3K-beta inhibitor GSK2636771 400 mg 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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40865033/

PIK3CB Inhibitor GSK2636771 in Cancers With PTEN ... Among 24 patients whose tumors had PTEN mutation/deletion but retained PTEN expression (arm N), seven patients (32%) achieved stable disease (SD) ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/PO-25-00265

PIK3CB Inhibitor GSK2636771 in Cancers With PTEN ... Of the 32 patients whose tumors had loss of PTEN protein expression (arm P), seven patients (22%) achieved SD, with two (6%) experiencing SD ≥ 6 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04439188

Testing GSK2636771 as a Potential Targeted Treatment in ... This phase II MATCH treatment trial identifies the effects of GSK2636771 in patients whose cancer has a complete loss of PTEN expression.

4. asco.org asco.org/abstracts-presentations/ABSTRACT372712

Phase I/II study of the selective PI3Kβ inhibitor ... In preclinical PTEN loss models, selective PI3Kβ inhibitor enhanced survival and the frequency of intratumoral T cells.

5. aacrjournals.org aacrjournals.org/clincancerres/article/23/19/5981/263954/A-First-Time-in-Human-Study-of-GSK2636771-a

A First-Time-in-Human Study of GSK2636771, a ... GSK2636771 is a potent, selective inhibitor of PI3Kβ that exhibits antitumor activity in PTEN-deficient cancers. A, Chemical structure of GSK2636771. B, The ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT316215

Safety results from phase I/II study of the PI3Kβ inhibitor ... Background: Checkpoint inhibitors (CPI) have improved survival and long-term disease control in 35-40% of pts with MM. Many pts derive no clinical benefit ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.5052

Phase I/II study of the selective PI3Kβ inhibitor ... GSK2636771 plus pembrolizumab had an acceptable safety and tolerability profile. The combination showed promising preliminary antitumor activity and durable ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04439188?term=AREA%5BConditionSearch%5D(cancer)%20AND%20AREA%5BBasicSearch%5D(PI3K%20inhibitor)&rank=4

Testing GSK2636771 as a Potential Targeted Treatment in ... This phase II MATCH treatment trial identifies the effects of GSK2636771 in patients whose cancer has a complete loss of PTEN expression.

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)03699-1/fulltext

1085P Ph I/II study of PI3K-β inhibitor GSK2636771 (G771) ... PTEN loss, which occurs in up to 30% of MM pts, activates the PI3K-AKT pathway and correlates with decreased tumor infiltrating lymphocytes (TIL) and lower ...