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

10 Participants Needed

Trial Summary

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.

What data supports the effectiveness of PD-1 inhibitors like Nivolumab and Pembrolizumab in treating Hodgkin's Lymphoma?

Research shows that PD-1 inhibitors, such as Nivolumab and Pembrolizumab, are effective in treating relapsed or refractory Hodgkin's Lymphoma, leading to high response rates and prolonged survival. These drugs help the immune system recognize and attack cancer cells, showing significant activity even in patients who have not responded to other treatments. ^{1 2 3 4 5}

Is the combination of PD-1 inhibitors and CAR T cell therapy safe for treating Hodgkin's Lymphoma?

PD-1 inhibitors like pembrolizumab and nivolumab have been shown to be generally safe in humans, with common side effects including fatigue, rash, and hypothyroidism. Serious side effects are less common, and the treatment has been well-tolerated in patients with relapsed or refractory lymphoma. ^{5 6 7 8 9}

How is the PD-1 Inhibitors + CAR T Cell Therapy treatment different for Hodgkin's Lymphoma?

This treatment is unique because it combines PD-1 inhibitors, which help the immune system recognize and attack cancer cells, with CAR T cell therapy, which involves modifying a patient's own T cells to better target cancer. This dual approach aims to enhance the immune response against Hodgkin's Lymphoma more effectively than using either treatment alone. ^{2 3 5 10 11}

What is the purpose of this trial?

LCCC1852-ATL is a prospective 2-arm study designed to determine if chimeric antigen receptor T (CAR-T) cells result in immunomodulation which can be subsequently exploited by programmed cell death protein 1 (PD-1) antibodies to achieve clinical responses in subjects with relapsed/refractory (r/r) classical Hodgkin Lymphoma (cHL).

Research Team

Natalie S. Grover

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Checkpoint inhibitors in Hodgkin's lymphoma. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Management of relapsed/refractory classical Hodgkin lymphoma in transplant-ineligible patients. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the Treatment of Relapsed and Refractory Classical Hodgkin Lymphoma After Autologous Transplant and in Transplant-Naïve Patients. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. Switzerland 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. [2020]

9. England pubmed.ncbi.nlm.nih.gov

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

10. United States pubmed.ncbi.nlm.nih.gov

Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Targeting Immune System Alterations in Hodgkin Lymphoma. [2020]