Pembrolizumab + Chemotherapy for B-Cell Lymphoma

Overseen By Justin Kline, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Pregnancy, Autoimmune disease, HIV, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining pembrolizumab (also known as KEYTRUDA, an immunotherapy drug) with R-CHOP chemotherapy for individuals with untreated diffuse large B-cell lymphoma, a type of blood cancer. Researchers aim to understand the disease's causes and patient responses to this treatment combination. The trial seeks participants diagnosed with diffuse large B-cell lymphoma who have not yet received any treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you cannot be on certain treatments like chronic systemic steroids or have received certain therapies recently. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that pembrolizumab combined with R-CHOP chemotherapy is likely to be safe for humans?

Research shows that combining pembrolizumab with the R-CHOP chemotherapy treatment is promising in terms of safety. In earlier studies, most patients experienced manageable side effects. About 61% of patients had some side effects, but these were mostly mild. Importantly, no patients stopped treatment because of these side effects.

Additionally, pembrolizumab with R-CHOP has led to lasting positive results, especially in patients whose tumors have a protein called PD-L1, which helps the immune system fight cancer cells. This indicates the treatment is not only effective but also well-tolerated in these cases.

Overall, evidence supports that this combination can be safely given to patients, though some mild side effects might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining pembrolizumab with the R-CHOP protocol for treating B-cell lymphoma because it introduces a new mechanism of action. Pembrolizumab is an immunotherapy drug that works by blocking the PD-1 pathway, which helps the immune system detect and attack cancer cells more effectively. This is different from the standard R-CHOP regimen, which uses a mix of chemotherapy drugs to directly kill cancer cells. By adding pembrolizumab, there's potential for a more robust immune response, possibly leading to better outcomes for patients.

What evidence suggests that pembrolizumab combined with R-CHOP could be an effective treatment for B-cell lymphoma?

This trial will evaluate the combination of pembrolizumab with R-CHOP chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL). Studies have shown that this combination has led to lasting positive results, with 83% of patients not experiencing cancer progression over two years. This treatment appears most effective for patients whose tumors express the protein PD-L1. The side effects are generally mild to moderate, making the treatment's safety manageable. These findings suggest that the treatment holds promise for individuals with this type of lymphoma. ^{1 2 3 5 6}

Who Is on the Research Team?

Justin Kline, MD

Principal Investigator

University of Chicago Medicine

Are You a Good Fit for This Trial?

Adults with untreated non-germinal center diffuse large B cell lymphoma or high-grade B cell lymphoma, not pregnant or breastfeeding, willing to use contraception. Must have measurable disease and adequate organ function. Cannot have had prior anti-lymphoma therapy or certain other treatments, no active infections like HIV or hepatitis, and no history of severe hypersensitivity to trial drugs.

Inclusion Criteria

- Not a woman of childbearing potential (WOCBP) OR

I have a lymphoma lesion larger than 1.5 cm long and 1.0 cm wide.

I agree to use contraception and not donate sperm for 120 days after my last treatment dose.

Exclusion Criteria

I have previously undergone treatment for lymphoma.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

I have a history of Hepatitis B or an active Hepatitis C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab in combination with R-CHOP chemotherapy regimen

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

23 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• R-CHOP Protocol

Trial Overview The study is testing the effectiveness of pembrolizumab combined with R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in treating patients with specific types of B cell lymphoma that haven't been treated before.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 2 Interventions

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+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37926672/

Pembrolizumab With R-CHOP in Previously Untreated DLBCL PR-CHOP has led to durable responses in most patients, with the best outcomes in PD-L1-expressing disease. Furthermore, the safety profile was manageable, ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.7561

Long-term efficacy and safety of pembrolizumab with R- ... At 5 year follow-up, pembrolizumab plus R-CHOP has led to durable responses in most patients with the best outcomes in PDL1-expressing disease.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32030732/

Pembrolizumab with R-CHOP in previously untreated diffuse ... With 25·5 months of median follow-up, 2-year progression-free survival (PFS) is 83%. PD-L1 expression was associated with non-GCB subtype, and improved PFS and ...

4. ashpublications.org ashpublications.org/blood/article/130/3/267/36926/Safety-and-tolerability-of-pembrolizumab-in

Safety and tolerability of pembrolizumab in patients with ... Eleven patients (61%) experienced drug-related adverse events (mostly grade 1-2); none discontinued treatment due to adverse events. ORR was 41% (7/17); 6 ...

5. ash.confex.com ash.confex.com/ash/2023/webprogram/Paper185160.html

An Open Label Phase II Study of Pembrolizumab and ... The combination of Pembrolizumab and Rituximab is predicted to be synergistic, and in non-randomised trials in other B-cell lymphoma histologies ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119846414

Pembrolizumab (MK-3475) in Combination with Standard ... We report preliminary results of the first known prospective trial of anti-PD1 therapy with anthracycline chemotherapy in lymphoma.