Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

GSK2636771

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Phase I: Participants receive the lowest dose level of GSK2636771. Each new group receives a higher dose of GSK2636771 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of GSK2636771 is found. Participants receive the same dose level of Pembrolizumab.

Phase II: Participants receive GSK2636771 at the highest dose that was tolerated in Phase 1. Participants receive the same dose level of Pembrolizumab.

Phase I Starting Dose of GSK2636771: 300 mg by mouth given for 21 days.

Phase II Dose of GSK2636771: Maximum tolerated dose from Phase I.

Phase I and II Dose of Pembrolizumab: 200 mg given by vein every 3 weeks.

Hussein Tawbi, MD, PHD

The goal of this clinical research study is to learn if GSK2636771 given in combination with pembrolizumab can help to control the disease in patients with refractory (has not responded to treatment) metastatic melanoma. The safety of this drug combination will also be studied.

This is an investigational study. Pembrolizumab is FDA approved and commercially available and FDA approved for the treatment of several types of cancer, including melanoma. GSK2636771 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drugs are designed to work.

Up to 41 participants will be enrolled in this study. All will take part at MD Anderson.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 3 groups of 3-6 participants will be enrolled in Phase 1 of the study, and up to 35 participants will be enrolled in Phase 2.

If you have metastatic cancer, you may be enrolled in Phase 1 of this study. If you have metastatic melanoma, you may be enrolled in Phase 1 or Phase 2 of this study.

If you are enrolled in Phase 1, the dose of GSK2636771 in combination with pembrolizumab you receive will depend on when you join this study. The first group of participants will receive the lowest dose level of GSK2636771. Each new group will receive a higher dose of GSK2636771 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of GSK2636771 is found.

If you are enrolled in Phase 2, you will receive GSK2636771 at the highest dose that was tolerated in Phase 1.

All participants will receive the same dose level of pembrolizumab.

Study Drug Administration:

Every study cycle is 21 days.

* You will take GSK2636771 by mouth every day for 21 days.
* You will receive pembrolizumab by vein for 30 minutes one (1) time on Day 1 of every cycle.

You should receive the study drugs at least 1 hour before or 2 hours after eating.

Length of Study:

You may receive the study drugs for up to 2 years. If the doctor thinks it is in your best interest, you may continue to receive either GSK2636771 or pembrolizumab for 1 more year. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the Follow-Up Visits.

Study Visits:

On Day 1 of Cycles 1, 3, 5, and 7:

* You will have a physical exam.
* You will have an EKG. If the doctor thinks it is needed, you will also have an ECHO and MUGA scan.
* Blood (about 3 teaspoons) and urine will be collected for routine tests.
* Blood (about 2 tablespoons) will be drawn for pharmacokinetic (PK) testing before the dose, at 30 minutes, 1, 2, 3, 4, 6, and 24 hours after the dose. (Cycle 1 only). PK testing measures the amount of study drug in the body at different time points.
* Blood (about 2 tablespoons) will be drawn for immune function testing (Cycles 3 \& 5 only).
* You will have a PET/CT scan or MRI to check the status of the disease (Cycle 5 only and then every 12 weeks after that).
* If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

On Day 1 of Cycles 2, 4, 6, 8 and beyond:

* You will have a physical exam.
* Blood (about 1½ teaspoon) and urine will be collected for routine tests.
* Blood (about 1 teaspoon) will be drawn for PK testing before the dose. (Cycle 2 only)
* If the doctor thinks it is needed, you will have an ECHO and MUGA scan.
* If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

On Day 1 of Cycles 2, 3, and 5, and every 12 weeks after that, you will be asked to have a core biopsy. Only 1 of these will be required, and the others will be optional. Though it is preferred that this be performed at Cycle 2, you and your doctor will choose which of these biopsies will be the required one.

Every 12 weeks after Cycle 5, blood (about 2½ tablespoons) will be drawn for immune system testing.

End of Study Dosing Visit:

After you stop receiving the study drugs:

* You will have a physical exam.
* If the doctor thinks it is needed, you will have an ECHO and MUGA scan.
* Blood (about 1 teaspoon) and urine will be collected for routine tests.
* If the disease got worse while you are on study, you may have a core biopsy.
* If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

Follow-Up Period:

Up to 30 days after the End-of-Study Dosing Visit and every 6 weeks:

* You will have a physical exam.
* Blood (about 2 tablespoons) and urine will be collected for routine tests.
* If the doctor thinks it is needed, you will have an ECHO and MUGA scan.
* If you can become pregnant, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

One (1) time every 12 weeks:

* You will have a PET/CT) scan or MRI to check the status of the disease.
* You will be called by a member of the study staff to check your health. These calls should last about 5 minutes each time.

Treatment Beyond Progression:

If the disease appears to be getting worse or the tumors appear to be getting larger, you may still be able to receive the study drug if you and your doctor decide it is in your best interest. Sometimes the disease appears to get worse but the study drug is actually working.

However, there are risks of continuing to receive the study drug because the disease may actually be getting worse. You are still at risk for side effects due to the study drug. This could also delay starting other treatments. The disease may get worse to the point that you are no longer able to receive other treatments.

If you choose to receive the study drug after the disease gets worse, you will continue to have study visits. The study doctor will discuss this option with you.

Alcohol and Activity Restriction:

On days when you have multiple PK blood draws, you should not have alcohol for at least 24 hours before your dose of study drug.

You should not exercise for 48 hours before each PK and/or routine testing blood draw.

Study of the Selective PI3K-Beta Inhibitor GSK2636771 in Combination With Pembrolizumab in Patients With Metastatic Melanoma and PTEN Loss

Phase I/II Study of the Selective PI3K-Beta Inhibitor GSK2636771 in Combination With Pembrolizumab in Patients With Metastatic Melanoma and PTEN Loss

Maximum-tolerated dose defined as the highest dose where ≤ 1 out of 6 participants experiences dose limiting toxicities (DLTs).

Objective Response Rate (ORR) determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in metastatic melanoma.

Overall survival (OS) defined from treatment start date to date of death for any cause.

National Cancer Institute (NCI)

National Institutes of Health (NIH)

Merck Sharp & Dohme LLC

GlaxoSmithKline

M.D. Anderson Cancer Center

GSK2636771 single dose and then daily dosing after approximately 1 week

GSK2636771 single dose and then daily dosing starting on Day 4

GSK Clinical Trials

The study consists of a pre-screening period to determine if the subject's tumor has PTEN deficiencies. Subjects then continue into the screening phase for Part 1, 2, or 3, as appropriate. In Part 1, subjects will then receive a single dose of 25 mg. After analysis of 24 hour pharmacokinetic (PK) samples, subjects may receive continuous dosing or receive a single modified dose. In Part 2, subjects will be enrolled and dose escalation will occur in a 3+3 design. Subjects will receive a single dose on Day 1, and then begin continuous daily dosing after collection of a 72-hour PK sample. Additional subjects may be enrolled at lower dose levels for assessment of pharmacodynamic response. In Part 3, up to two tumor-specific expansion cohorts will be enrolled and receive the MTD or BED as defined in Part 2. A minimum of 12 and a maximum of 20 evaluable subjects will be enrolled in each cohort. Interim monitoring for futility will be incorporated after response data from 12 subjects are available. In addition, up to 20 evaluable subjects will be enrolled into Part 3 -Signal-finding Expansion Cohort at the MTD or BED as defined in Part 2. All subjects in all parts/cohorts will receive daily dosing until withdrawal or unacceptable toxicity. All subjects in all parts/cohorts will receive daily dosing until withdrawal or unacceptable toxicity.

A Phase I/IIa, First Time in Human, Study of GSK2636771 in Subjects With Advanced Solid Tumors With Phosphatase and Tensin Homolog (PTEN) Deficiency

A Phase I/IIa, First Time in Human, Open-label Dose-escalation Study of GSK2636771 in Subjects With Advanced Solid Tumors With PTEN Deficiency

IPD for this study will be made available via the Clinical Study Data Request site.

Pharmacokinetic parameters including AUC, Cmax, tmax, and t1/2; adverse events, serious adverse events, changes in laboratory values, ECG parameters, and vital signs; median and maximum AUC(0-24)

Pharmacokinetic parameters including AUC, Cmax, tmax, and t1/2; adverse events, serious adverse events, changes in laboratory values, ECG parameters, and vital signs; dose-limiting toxicities and/or biological activity in tumor or anti-tumor efficacy

Overall Response Rate (ORR): defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) as per RECIST 1.1 criteria

adverse events, serious adverse events, changes in laboratory values, ECG parameters, and vital signs

change from baseline in PD biomarkers which may include: platelet function, pathway proteins in tumor biopsy specimens and surrogate tissue, and/or soluble or cellular markers found in blood; ORR, defined as the percentage of subjects with a confirmed CR or PR as per RECIST 1.1 criteria; Duration of Response: defined, for the subset of subjects with a confirmed CR or PR, as the time from first documented evidence of CR or PR until first documented disease progression or death due to any cause

change from baseline in PD biomarkers which may include: platelet function, pathway proteins in tumor biopsy specimens/surrogate tissue, and/or soluble or cellular markers found in blood; change from baseline in circulating tumor cells (CTC) concentration in prostate cancer subjects; CTC Response Rate: defined as the number of subjects going from \>5 CTCs to \<5 CTCs per 7.5ml of blood (prostate cancer subjects only); Duration of Response; Progression Free Survival: defined as interval between date of first dose and earliest date of disease progression or death due to any cause

population pharmacokinetic parameters for GSK2636771 following single- and repeat-dose oral administration, including AUC and Vdss, and absorption rate constant (ka)

adverse events and changes in laboratory values, ECG parameters, and vital signs following repeat-dose oral administration of GSK2636771

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Increasing dose levels of GSK2636771 (300 mg or 400 mg once daily) in combination with a fixed dose of paclitaxel (80 mg/m2 on Days 1, 8 and 15 of a 28-day treatment cycle)

Increasing dose levels of GSK2636771 (300 mg or 400 mg once daily)

fixed dose of paclitaxel (80 mg/m2 on Days 1, 8 and 15 of a 28-day treatment cycle)

Sun Young Rha

This is a Phase Ib/IIa, open-label, non-randomized, dose-escalation, multi-center study to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of oral GSK2636771 in combination with intravenous (IV) paclitaxel in two independent subject populations: subjects with PTEN-deficient, advanced gastric adenocarcinoma. This study will be conducted in two phases: the Dose Escalation Phase and the Dose Expansion Phase. The Dose Escalation Phase (Phase Ib) is designed to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) of GSK2636771 administered in combination with paclitaxel. The Dose Expansion Phase (Phase IIa) will further evaluate the safety and clinical activity of the RP2D as determined in the Dose Escalation Phase.

PI3Kβ Selective Inhibitor With Paclitaxel, Advanced Gastric Adenocarcinoma

A Phase Ib/IIa, Open-Label, Dose Finding Study to Evaluate the Safety, Pharmacokinetics and Clinical Activity of PI3Kβ Selective Inhibitor (GSK2636771) Administered in Combination With Paclitaxel in Advanced Gastric Adenocarcinoma Having Alterations in PI3K Pathway Genes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of the Selective PI3K-Beta Inhibitor GSK2636771 in Combination With Pembrolizumab in Patients With Metastatic Melanoma and PTEN Loss	NCT03131908	Melanoma and Ot... Metastatic Mela...	GSK2636771 Pembrolizumab	18 Years -	M.D. Anderson Cancer Center
A Phase I/IIa, First Time in Human, Study of GSK2636771 in Subjects With Advanced Solid Tumors With Phosphatase and Tensin Homolog (PTEN) Deficiency	NCT01458067	Cancer	GSK2636771	18 Years -	GlaxoSmithKline
A Phase I/IIa, First Time in Human, Study of GSK2636771 in Subjects With Advanced Solid Tumors With Phosphatase and Tensin Homolog (PTEN) Deficiency	NCT01458067	Cancer	GSK2636771	18 Years -	GlaxoSmithKline
PI3Kβ Selective Inhibitor With Paclitaxel, Advanced Gastric Adenocarcinoma	NCT02615730	Advanced Gastri...	GSK2636771 Paclitaxel	19 Years -	Yonsei University
PI3Kβ Selective Inhibitor With Paclitaxel, Advanced Gastric Adenocarcinoma	NCT02615730	Advanced Gastri...	GSK2636771 Paclitaxel	19 Years -	Yonsei University

Spots Global Cancer Trial Database for gsk2636771

Every month we try and update this database with for gsk2636771 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for gsk2636771

Every month we try and update this database with for gsk2636771 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for gsk2636771 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.