Magrolimab + Pembrolizumab for Hodgkin's Lymphoma

Recruiting at 1 trial location

Overseen By Austin Yeung

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: PD-1 inhibitors, CD47 antibodies

Disqualifiers: Autoimmune disorders, HIV, Hepatitis, 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

Compensation: Varies

Number of Visits: 3

Duration: 24 months

8 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety and efficacy of magrolimab in combination with pembrolizumab in patients with Hodgkin lymphoma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had a PD-1 inhibitor within 3 months before joining, and you must not be on chronic immunosuppression with prednisone at 10 mg or more daily.

What data supports the effectiveness of the drug Magrolimab + Pembrolizumab for treating Hodgkin's Lymphoma?

Pembrolizumab, one of the drugs in the treatment, has shown effectiveness in treating relapsed or refractory classical Hodgkin lymphoma, with studies indicating high response rates and long-term survival benefits. It has also been effective in other cancers, like non-small-cell lung cancer and melanoma, suggesting its potential in Hodgkin's Lymphoma. ^{1 2 3 4 5}

Is the combination of Magrolimab and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, and thyroid issues. Rarely, it may lead to serious immune-related problems like type 1 diabetes. Safety data for Magrolimab specifically in combination with Pembrolizumab is not provided here, but Pembrolizumab alone has been studied extensively. ^{3 6 7 8 9}

How is the drug combination of Magrolimab and Pembrolizumab unique for treating Hodgkin's Lymphoma?

The combination of Magrolimab and Pembrolizumab is unique because it combines two different mechanisms: Magrolimab targets cancer cells directly, while Pembrolizumab helps the immune system recognize and attack cancer cells by blocking the PD-1 pathway. This dual approach may offer a novel way to treat Hodgkin's Lymphoma compared to existing therapies. ^{1 3 4 10 11}

Research Team

Ranjana H Advani, MD

Principal Investigator

Stanford Universiy

Eligibility Criteria

Adults over 18 with relapsed or refractory classic Hodgkin Lymphoma (cHL) who've had at least two prior treatments can join. They must have a certain level of blood cells, organ function, and no recent severe illnesses or second cancers. Participants need to use effective birth control and not be pregnant.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Creatinine clearance > 40 mL/min per the Cockroft-Gault formula

I have undergone at least two different treatments for my condition.

Exclusion Criteria

I have had a stem cell transplant from a donor.

History of psychiatric illness or substance abuse likely to interfere with ability to comply with protocol requirements

I have had another cancer, but it has been in complete remission for at least a year, except for skin cancer or localized prostate cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive magrolimab and pembrolizumab according to the dosing schedule for up to 24 months

24 months

Regular visits as per dosing schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

2 visits (in-person)

Extension

Participants may continue treatment until disease progression, unacceptable toxicity, or bridge to stem cell transplantation

Long-term

Treatment Details

Interventions

• Magrolimab
• Pembrolizumab

Trial Overview The trial is testing the combination of Magrolimab and Pembrolizumab for safety and effectiveness in treating cHL. Patients will undergo PET/CT imaging to measure disease activity before and during treatment.

Participant Groups

Group I: Magrolimab (Hu5F9 G4) and pembrolizumab Experimental Treatment 3 Interventions

All subjects will have a baseline PET CT and excisional or core needle biopsy within 1 month of study enrollment and baseline electrocardiogram and laboratory studies within 1 week of study enrollment. All subjects will receive treatment with magrolimab and pembrolizumab according to the dosing schedule. Magrolimab IV given on cycle 1, 2 and 3. Pembrolizumab 200 mg IV given on Cycle 1, 2 and 3. Patients may continue to receive treatment on the study for a maximum of 24 months or until progression of disease, unacceptable toxicity, or bridge to stem cell transplantation (SCT).

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

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

Findings from Research

In patients with relapsed and refractory classical Hodgkin's lymphoma who have previously failed treatment with brentuximab vedotin, pembrolizumab significantly improves progression-free survival (PFS) compared to standard of care, with hazard ratios indicating a much lower risk of disease progression.

The study involved a systematic literature review and comparisons of outcomes from pembrolizumab's KEYNOTE-087 trial against an observational study of standard care, confirming that pembrolizumab is a more effective treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. Keeping, S., Wu, E., Chan, K., et al.[2019]

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]

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]

In a phase 3 study involving 304 patients with relapsed or refractory classical Hodgkin lymphoma, pembrolizumab demonstrated a median progression-free survival of 13.2 months, significantly longer than the 8.3 months observed with brentuximab vedotin, indicating its superior efficacy.

While both treatments had associated adverse events, pembrolizumab's safety profile was consistent with previous studies, with serious treatment-related events occurring in 16% of patients, supporting its use as a preferred option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Kuruvilla, J., Ramchandren, R., Santoro, A., et al.[2021]

In a phase II study of 39 patients with relapsed or refractory classical Hodgkin lymphoma, the combination of pembrolizumab with gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) resulted in a remarkable overall response rate of 100% and a complete response rate of 95%.

The treatment was well-tolerated, with most adverse events being mild (grade 1 or 2), and 95% of patients successfully proceeded to high-dose therapy and autologous hematopoietic cell transplantation, with all transplanted patients remaining in remission at a median follow-up of 13.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma. Moskowitz, AJ., Shah, G., Schöder, H., et al.[2023]

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 (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]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

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]

In a phase 2 trial involving 30 patients with newly diagnosed classical Hodgkin lymphoma, pembrolizumab monotherapy led to a complete metabolic response (CMR) in 37% of patients, demonstrating its efficacy as an initial treatment.

The combination of pembrolizumab followed by AVD chemotherapy was well tolerated, with no disease progression or deaths reported during a median follow-up of 22.5 months, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. Allen, PB., Savas, H., Evens, AM., 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. [2019]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. [2021]

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

Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma. [2023]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of diffuse large B-cell lymphoma. [2020]