Pembrolizumab + TGR-1202 for Non-Hodgkin's Lymphoma

Not currently recruiting at 2 trial locations

Overseen By Cancer Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Active infection, Autoimmune disease, HIV, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two drugs, pembrolizumab (an immunotherapy drug) and TGR-1202, in treating Non-Hodgkin's Lymphoma (a type of blood cancer) when previous treatments have failed. The study begins with TGR-1202 for six weeks, and if tolerated, pembrolizumab will be added for additional cycles. The researchers aim to determine if this combination can help patients manage their cancer more effectively. Individuals who have undergone at least one round of standard therapy for their B-cell NHL or CLL and still have the disease might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have found pembrolizumab generally safe for people with certain types of lymphoma, including primary mediastinal large B-cell lymphoma. The FDA has approved it for this use, indicating its safety.

TGR-1202, also known as umbralisib, has been tested alone in other studies. Some patients tolerated it well, but reports of side effects exist. These side effects can include changes in lab test results, so doctors must monitor patients closely.

Research continues to fully understand the safety of using pembrolizumab and TGR-1202 together. Early testing focuses on ensuring the treatment's safety, and this study aims to find the right dose to minimize side effects. If a lower dose of TGR-1202 isn’t well-tolerated, the plan involves adjusting the dosage to ensure safety.

While some positive safety information exists, especially for pembrolizumab, the safety of TGR-1202 combined with pembrolizumab remains under careful study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pembrolizumab and TGR-1202 for treating Non-Hodgkin's Lymphoma because they bring a fresh approach to tackling the disease. Unlike traditional chemotherapy and immunotherapy options, pembrolizumab is a type of immunotherapy that works by blocking the PD-1 pathway, effectively unleashing the immune system to attack cancer cells. TGR-1202, on the other hand, targets the PI3K-delta pathway, which is often overactive in cancer cells, helping to halt cancer growth. This combination is promising because it combines two mechanisms of action, potentially leading to a more effective treatment with complementary effects.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

Research shows that pembrolizumab, a type of immunotherapy, may help treat certain aggressive forms of non-Hodgkin's lymphoma by blocking a protein that prevents the immune system from attacking cancer cells. TGR-1202, also known as Umbralisib, has been tested for safety and effectiveness on its own for similar conditions. As a PI3K-inhibitor, it targets a specific pathway that cancer cells use to grow. In this trial, all participants will receive a combination of pembrolizumab and TGR-1202. Combining these treatments could enhance effectiveness by using both the immune system and targeted therapy to fight lymphoma. Early studies suggest this combination might offer a new option for patients with relapsed or difficult-to-treat forms of the disease. ^{1 3 5 6 7}

Who Is on the Research Team?

Michael Thirman, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

Adults over 18 with relapsed/refractory B-cell NHL or CLL who've had at least one prior standard therapy can join. They must have measurable disease, be able to consent, and have good organ function and performance status. Women of childbearing potential must use birth control, as should men.

Inclusion Criteria

My organ functions are within the required range for treatment.

I agree to provide tissue samples for testing during and after treatment.

Female subject of childbearing potential should have a negative urine or serum pregnancy prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria

My brain or nervous system cancer is stable, and I haven't used steroids in the last 7 days.

I have a history of active tuberculosis.

Hypersensitivity to pembrolizumab or any of its excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Treatment

Participants receive TGR-1202 at a dose of 600mg or 800mg daily for 6 weeks to assess tolerability

6 weeks

Regular visits for monitoring

Combination Treatment

Participants receive pembrolizumab every 3 weeks for 8 cycles along with TGR-1202

24 weeks

Visits every 3 weeks

Maintenance Treatment

Participants continue on TGR-1202 at the maximum tolerated dose until disease progression

Until disease progression

Follow-up

Participants are monitored for disease response, adverse events, and survival

Minimum of 2 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• TGR-1202

Trial Overview The trial tests TGR-1202 in two doses (600mg or 800mg daily) for six weeks followed by pembrolizumab every three weeks for eight cycles. The study uses a '3+3 design' to find the safest dose that shows benefits while minimizing early toxicities.

How Is the Trial Designed?

Group I: TGR-1202 and pembrolizumab Experimental Treatment 2 Interventions

All patients will receive TGR-1202 and pembrolizumab. Patients will start receiving TGR-1202 daily for 6 weeks (2 cycles). Pembrolizumab will be given every 3 weeks for 8 cycles. If the daily dose of TGR-1202 (dose level 1) is tolerated in the first cohort the dose will be increased which is the only and final dose escalation. If TGR-1202 is not tolerated the dose will be decreased.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant clinical efficacy in treating Hodgkin Lymphoma and promising early results in certain subtypes of Non-Hodgkin Lymphoma, particularly those with genetic similarities to HL.

Current data suggest that pembrolizumab has a favorable safety profile and efficacy as a single agent in treating diffuse large B cell lymphomas, with future strategies likely to focus on biomarker-driven approaches and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. Sheikh, S., Kuruvilla, J.[2020]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

In a study of 59 patients with relapsed/refractory extranodal natural killer/T-cell lymphoma treated with pembrolizumab, the overall response rate was 40.7%, with 28.8% achieving a complete response, indicating its potential efficacy as a salvage therapy.

While pembrolizumab showed modest effectiveness, it was associated with some grade 3 or 4 adverse events in 20.3% of patients, with neutropenia being the most common, suggesting that while it can be beneficial, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. Lee, JY., Kwon, JH., Hur, JY., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Citations

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Combination of Pembrolizumab With TGR-1202 in Patients ... This study will be a standard 3+3 design with a lead in of TGR-1202 at dose of 600mg (dose level 1) or 800mg daily (dose level 2) for 6 weeks, i.e. 2 cycles ...

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Breakthrough therapies in B-cell non-Hodgkin lymphoma The purpose of this comprehensive review is to provide a detailed analysis of the breakthrough agents in the field, with a focus on recent clinical data.

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A Phase 2 Study to Assess the Efficacy and Safety of TGR ... This research study will evaluate the safety and efficacy of a study drug called Umbralisib (also known as TGR-1202) alone as a possible treatment for ...

5. aacr.org aacr.org/patients-caregivers/progress-against-cancer/immunotherapeutic-non-hodgkin-lymphoma-pembrolizumab-keytruda/

A New Immunotherapeutic for Non-Hodgkin Lymphoma The FDA expanded the use of the immunotherapy pembrolizumab for certain patients with an aggressive type of non-Hodgkin lymphoma.

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Combination of Pembrolizumab With TGR-1202 in Patients ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8864656/

Safety and activity of pembrolizumab in combination with ... Combination therapy with pembrolizumab and rituximab was well tolerated in patients with relapsed/refractory follicular lymphoma. In this single-arm, ...