PD-1 Inhibitors + CAR T Cell Therapy for Hodgkin's Lymphoma

Overseen By Caroline Babinec

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must be taking: Anti-PD-1 therapy

Must not be taking: Systemic corticosteroids

Disqualifiers: Active infection, Additional malignancy, 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: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with relapsed or hard-to-treat classical Hodgkin lymphoma. It examines the effectiveness of combining CAR T-cell therapy, which uses modified immune cells to target cancer, with PD-1 inhibitors, such as nivolumab or pembrolizumab, that help the immune system attack cancer cells. Participants are divided into two groups: those who have previously received CAR T-cell therapy and those who have not. Individuals who have experienced progression after standard treatments for classical Hodgkin lymphoma might be suitable candidates. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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 participate if you are using high doses of corticosteroids or other immunosuppressive medications. 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?

Research has shown that nivolumab and pembrolizumab are generally well-tolerated by people with Hodgkin's lymphoma. These treatments, known as immune checkpoint inhibitors, are often used when the lymphoma returns or doesn't respond to other treatments.

One study found that pembrolizumab effectively fights cancer. Another study showed that nivolumab works well for people whose cancer didn't respond to previous treatments.

Both treatments have been safely used in past patients. Common side effects include tiredness, rash, and itching, which are usually manageable. Serious side effects are less common but can occur.

Overall, these treatments are generally well-tolerated, but discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining PD-1 inhibitors like nivolumab and pembrolizumab with CAR T cell therapy for Hodgkin's lymphoma because this approach could enhance the immune system's ability to fight cancer. Unlike traditional chemotherapy or radiation, which can harm healthy cells alongside cancer cells, PD-1 inhibitors work by blocking a pathway that cancer cells use to hide from the immune system, allowing T cells to attack the cancer more effectively. Additionally, CAR T cell therapy involves modifying a patient's own T cells to better recognize and destroy cancer cells. This dual approach could potentially improve outcomes for patients who have relapsed after other treatments, offering a new hope where previous options were limited.

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

Research has shown that PD-1 inhibitors, such as nivolumab and pembrolizumab, effectively treat relapsed or hard-to-treat classical Hodgkin's lymphoma (cHL). In this trial, participants will receive either nivolumab or pembrolizumab, depending on their treatment arm. One study found that when combined with chemotherapy, nivolumab led to a 92% survival rate in patients with advanced Hodgkin lymphoma. Another study demonstrated that pembrolizumab was highly effective at shrinking or eliminating tumors. Nivolumab has also proven successful in real-world use, supporting its positive results in clinical trials. These drugs enhance the immune system's ability to fight cancer. ^{3 4 5 6 7}

Who Is on the Research Team?

Natalie S. Grover

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with classical Hodgkin lymphoma that's come back or hasn't responded to treatment. They must have tried at least three prior therapies and either had or not had CD30 CAR-T therapy. Participants need to give informed consent, be ready for standard anti-PD-1 therapy, and provide blood samples.

Inclusion Criteria

I have been diagnosed with classical Hodgkin lymphoma.

I am starting standard anti-PD-1 therapy as advised by my oncologist.

I had a stem cell transplant and understand the risks of anti-PD-1 therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anti-PD-1 therapy (nivolumab or pembrolizumab) after progression on CD30 CAR-T cell therapy

12 weeks

Visits on Day 1, Day 21, and Day 42

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab
• Pembrolizumab

Trial Overview The study is testing if CAR-T cell therapy can make the immune system respond better to PD-1 inhibitors like Nivolumab and Pembrolizumab in patients with relapsed/refractory Hodgkin lymphoma. It has two groups: one previously treated with CD30 CAR-T cells and one without such treatment.

How Is the Trial Designed?

Group I: Arm 2: Relapse with no Prior CD30 CAR-T Therapy Experimental Treatment 2 Interventions

Subjects with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) who have previously progressed on anti-PD-1 therapy, have not received a CD30 CAR-T cell therapy and have evidence of progression. Subjects will be offered anti-PD-1 therapy (nivolumab or pembrolizumab, at the discretion of treating oncologist), as per standard of care in r/r cHL.

Group II: Arm 1: Relapse After Prior CD30 CAR-T Therapy Experimental Treatment 2 Interventions

Subjects with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) who have previously progressed on anti-PD-1 therapy, have received a CD30 CAR-T cell therapy and have evidence of progression. Subjects will be offered anti-PD-1 therapy (nivolumab or pembrolizumab, at the discretion of treating oncologist), as per standard of care in r/r cHL.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

American Society of Clinical Oncology

Collaborator

Trials

40

Recruited

148,000+

Published Research Related to This Trial

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

In a study of 55 patients with relapsed/refractory Hodgkin's Lymphoma, Pembrolizumab showed a high response rate of 74.5%, with a complete response in 32.7% of patients, indicating its efficacy before autologous stem cell transplantation.

The 12-month overall survival rate was 92%, and the progression-free survival rate was 51%, demonstrating reasonable safety and promising survival outcomes for patients treated with checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the Treatment of Relapsed and Refractory Classical Hodgkin Lymphoma After Autologous Transplant and in Transplant-Naïve Patients. Halahleh, K., Al Sawajneh, S., Saleh, Y., et al.[2022]

In a study involving 51 patients with newly diagnosed advanced-stage classic Hodgkin lymphoma, nivolumab followed by a combination therapy (N-AVD) showed an impressive objective response rate of 84%, with 67% of patients achieving complete remission.

The treatment was generally well-tolerated, with 59% of patients experiencing grade 3 to 4 treatment-related adverse events, but most were manageable, and the 9-month modified progression-free survival rate was 92%, indicating strong efficacy and safety for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. Ramchandren, R., Domingo-Domènech, E., Rueda, A., et al.[2021]

In a phase Ib study involving 31 patients with relapsed or refractory Hodgkin lymphoma, pembrolizumab showed a favorable safety profile with only 16% experiencing grade 3 drug-related adverse events and no grade 4 adverse events or treatment-related deaths.

The treatment resulted in a 16% complete remission rate and a 65% overall response rate, with most responses lasting over 24 weeks, indicating that pembrolizumab may be an effective option for patients who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. Armand, P., Shipp, MA., Ribrag, V., et al.[2022]

Nivolumab and pembrolizumab, both anti-PD-1 therapies, show promising efficacy in treating relapsed or refractory lymphoma, with an overall response rate of 58% and a 6-month overall survival rate of 96% across 10 studies involving 718 patients.

While both treatments have tolerable adverse effects, pembrolizumab is associated with fewer instances of fatigue and rash compared to nivolumab, and patients with Hodgkin lymphoma respond better to treatment than those with non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Anti-PD-1 Monoclonal Antibodies in Patients With Relapsed or Refractory Lymphoma: A Meta-Analysis of Prospective Clinic Trails. Zhou, H., Fu, X., Li, Q., et al.[2020]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

The addition of brentuximab vedotin and PD-1 inhibitors like nivolumab and pembrolizumab has improved treatment outcomes for patients with relapsed/refractory classical Hodgkin lymphoma, potentially leading to cures in some cases.

For patients unable to undergo intensive treatments, using a personalized approach with sequential therapies can extend survival while maintaining a reasonable quality of life, and participation in clinical trials for new therapies is encouraged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of relapsed/refractory classical Hodgkin lymphoma in transplant-ineligible patients. Mehta-Shah, N., Bartlett, NL.[2023]

In a phase 2 trial involving 30 patients with untreated advanced-stage classic Hodgkin lymphoma, nearly two-thirds achieved complete or near-complete metabolic responses after receiving pembrolizumab alone, and all patients achieved complete responses after subsequent AVD chemotherapy, with a 100% overall survival rate at a median follow-up of 33.1 months.

The study found that all patients had genomic alterations in chromosome 9p24.1 and were positive for PD-L1, indicating that even low levels of PD-L1 expression can lead to effective responses to PD-1 blockade, suggesting a broad applicability of this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma. Allen, PB., Lu, X., Chen, Q., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39413375/

Nivolumab+AVD in Advanced-Stage Classic Hodgkin's ... N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin's lymphoma.

2. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/hodgkin-lymphoma-nivolumab-avd-first-line

Nivolumab and AVD the New Standard in Hodgkin ... Treatment with nivolumab and a three-drug chemotherapy regimen called AVD was better at eliminating cancer and keeping it at bay than the current standard ...

3. ashpublications.org ashpublications.org/blood/article/142/10/878/496370/Five-year-follow-up-of-KEYNOTE-087-pembrolizumab

Five-year follow-up of KEYNOTE-087: pembrolizumab ... Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1130634324001557

[Translated article] Real-world effectiveness and safety of ... Nivolumab in the treatment of relapsed or refractory classical Hodgkin's lymphoma has confirmed favourable effectiveness data in the study sample.

5. oncology-central.com oncology-central.com/nivolumab-improves-survival-and-reduces-long-term-side-effects-for-advanced-hodgkin-lymphoma-patients-2/

Nivolumab plus chemotherapy yields 92% survival rate for ... Advanced Hodgkin lymphoma patients who received chemotherapy alongside Opdivo (nivolumab) had a 92% survival rate and fewer side effects.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10602819/

Effectiveness and Safety of Pembrolizumab in Recurrent and ... Immune checkpoint inhibitor pembrolizumab, which targets PD-1, is now being commonly used as part of immunotherapy for recurrent and relapsed cHL.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03407144

NCT03407144 | Safety and Efficacy of Pembrolizumab (MK ... This study will examine the safety and efficacy of pembrolizumab (MK-3475) in combination with chemotherapy in children and young adults with newly diagnosed ...