Pembrolizumab + Hyaluronidase for Lymphoma

Recruiting at 35 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antiretrovirals, HBV antivirals

Must not be taking: Steroids, Monoclonal antibodies

Disqualifiers: Cardiovascular disease, Active malignancy, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 24 months

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment method for individuals with certain types of lymphoma, specifically those whose classical Hodgkin lymphoma or primary mediastinal large B-cell lymphoma has returned or did not respond to previous treatments. The study examines how the immune-boosting drug pembrolizumab, combined with the enzyme hyaluronidase, behaves in the body and its effectiveness. Participants will receive the treatment via injection every six weeks for up to two years. This trial may suit someone with relapsed or treatment-resistant lymphoma who has lived with the disease for some time. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or other immunosuppressive therapy within 7 days before the study starts, or if you have received certain cancer treatments recently. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that pembrolizumab coformulated with hyaluronidase is likely to be safe for humans?

Research shows that pembrolizumab is generally safe and well-tolerated by patients. Studies on individuals with certain types of lymphoma indicate that pembrolizumab has a manageable safety profile. While some side effects might occur, they are usually not serious and can be treated by doctors. Adding hyaluronidase to pembrolizumab appears to be as effective as administering pembrolizumab alone through an IV, where medicine is given directly into a vein. This is positive because it allows the treatment to be given as a quick shot under the skin, which is usually easier and faster. Although no serious safety issues have been reported, individual experiences can differ. Discuss potential risks and benefits with a doctor before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for relapsed or refractory classical Hodgkin lymphoma (rrCHL) and primary mediastinal B-cell lymphoma (rrPMBCL), which often involves chemotherapy or radiation, pembrolizumab coformulated with hyaluronidase offers a novel approach by combining an immune checkpoint inhibitor with an enzyme that enhances drug delivery. This formulation allows for subcutaneous injection, potentially making treatments more convenient and less invasive compared to traditional intravenous methods. Researchers are excited about this treatment because it could improve the body's immune response against cancer cells, providing a more targeted and possibly more effective option.

What evidence suggests that pembrolizumab coformulated with hyaluronidase might be an effective treatment for lymphoma?

Studies have shown that pembrolizumab effectively treats certain types of lymphoma, including relapsed or hard-to-treat classical Hodgkin lymphoma (cHL) and primary mediastinal large B-cell lymphoma (PMBCL). Pembrolizumab targets a protein called PD-1, which cancer cells use to evade the immune system. This targeting helps the immune system find and attack cancer cells more effectively. Research indicates that pembrolizumab can lead to significant tumor shrinkage in many patients with these conditions. In this trial, participants will receive pembrolizumab coformulated with hyaluronidase, which is being studied to facilitate subcutaneous administration. Early results suggest this new method works as well as the traditional intravenous method. ^{3 4 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with certain types of lymphoma that have come back or didn't respond to treatment. It's not clear what specific health conditions or other criteria might prevent someone from joining, as the exclusion criteria are not provided.

Inclusion Criteria

I am hepatitis B positive but have been on HBV therapy for 4 weeks with an undetectable viral load.

I had hepatitis C but completed treatment and now have no detectable virus.

Have a life expectancy of >3 months

Exclusion Criteria

I have fluid around my heart or in my lungs.

I have another cancer that has gotten worse or needed treatment in the last 2 years.

I have a serious heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab coformulated with hyaluronidase subcutaneous injection on Day 1 of each 6-week cycle for up to 18 cycles

Up to 24 months

1 visit every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for long-term safety and efficacy outcomes

Up to 48 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab Coformulated With Hyaluronidase

Trial Overview The study tests a new way to give pembrolizumab, a cancer drug, by injecting it under the skin with hyaluronidase. They want to see how the body processes this mix and if it helps shrink the cancer in Hodgkin Lymphoma and B-cell Lymphoma patients.

How Is the Trial Designed?

Group I: Pembrolizumab Coformulated With Hyaluronidase Experimental Treatment 1 Intervention

Participants with rrCHL and rrPMBCL receive pembrolizumab coformulated with hyaluronidase subcutaneous (SC) injection on Day 1 of each 6-week cycle (Q6W) for up to 18 cycles (approximately 2 years) until documented disease progression per investigator assessment.

Pembrolizumab Coformulated With Hyaluronidase is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as KEYTRUDA for:

• Melanoma
• Non-small cell lung cancer
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Primary mediastinal large B-cell lymphoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Melanoma
• Non-small cell lung cancer
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Primary mediastinal large B-cell lymphoma
• Cervical cancer
• Endometrial carcinoma

Approved in Canada as KEYTRUDA for:

• Melanoma
• Non-small cell lung cancer
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Primary mediastinal large B-cell lymphoma
• Cervical cancer
• Endometrial carcinoma

Approved in Japan as KEYTRUDA for:

• Melanoma
• Non-small cell lung cancer
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Primary mediastinal large B-cell lymphoma
• Cervical cancer
• Endometrial carcinoma

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead 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

Published Research Related to This Trial

In a phase 1 study involving 60 healthy subjects, bococizumab mixed with recombinant human hyaluronidase (rHuPH20) showed increased bioavailability, with higher peak concentrations and overall exposure compared to bococizumab alone.

Despite the increased bioavailability, the lipid-lowering effect of bococizumab was diminished when co-administered with rHuPH20, indicating that the combination did not enhance its therapeutic efficacy as expected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, and safety of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, in healthy subjects when administered in co-mixture with recombinant human hyaluronidase: A phase 1 randomized trial. Bass, A., Plotka, A., Mridha, K., et al.[2023]

The FeDeriCa study demonstrated that the subcutaneous formulation of pertuzumab and trastuzumab is non-inferior to the intravenous version in terms of serum drug levels, indicating it can effectively deliver the same therapeutic benefits in patients with HER2-positive early breast cancer.

Safety profiles were comparable between the subcutaneous and intravenous groups, with similar rates of serious adverse events, suggesting that the new formulation is a safe alternative for patients undergoing neoadjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Tan, AR., Im, SA., Mattar, A., et al.[2021]

Subcutaneous administration of rituximab, combined with recombinant human hyaluronidase, shows noninferior pharmacokinetics compared to the traditional intravenous infusion, making it a viable alternative for patients.

This new delivery method not only maintains equivalent clinical outcomes for treating B-cell malignancies like follicular lymphoma and chronic lymphocytic leukemia but also offers advantages in terms of patient preference, time efficiency, and cost savings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous rituximab with recombinant human hyaluronidase in the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia. Hill, SL., Davies, A.[2018]

A Phase I study involving 24 healthy volunteers found that intravenous administration of rHuPH20 (up to 30,000 U) was well tolerated, with no serious adverse events reported, indicating a favorable safety profile.

The pharmacokinetics showed that rHuPH20 was rapidly cleared from the plasma, with plasma hyaluronan concentrations increasing in a dose-dependent manner and returning to baseline within one week, suggesting effective metabolism and clearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Hyaluronidase PH20 Administered Intravenously in Healthy Volunteers. Printz, MA., Dychter, SS., DeNoia, EP., et al.[2022]

Atezolizumab administered subcutaneously (SC) showed noninferior drug exposure compared to intravenous (IV) administration in patients with non-small-cell lung cancer, indicating that SC could be a viable alternative to IV treatment.

Both SC and IV forms of atezolizumab demonstrated similar efficacy, safety, and immunogenicity profiles, with no new safety concerns identified, supporting the use of SC for improved treatment convenience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications. Burotto, M., Zvirbule, Z., Mochalova, A., et al.[2023]

Rituximab and hyaluronidase human is a newly approved subcutaneous formulation of rituximab for treating certain types of blood cancers, including follicular lymphoma and chronic lymphocytic leukemia.

This new formulation shows noninferior pharmacokinetics and similar treatment outcomes compared to traditional intravenous rituximab, potentially offering greater convenience for patients and more efficient use of healthcare resources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Rituximab in Follicular Lymphoma, Chronic Lymphocytic Leukemia, and Diffuse Large B-Cell Lymphoma. Yelvington, BJ.[2020]

In a 24-week study involving 619 patients with moderate to severe rheumatoid arthritis, tocilizumab significantly improved disease activity, with 30.1% of patients achieving an ACR50 response compared to only 11.2% in the placebo group.

Tocilizumab demonstrated rapid efficacy, with improvements in patient-reported outcomes and disease activity scores observable as early as one week into treatment, while maintaining a safety profile consistent with previous findings, including a higher rate of serious infections compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis and a previous inadequate response to disease-modifying antirheumatic drugs: the ROSE study. Yazici, Y., Curtis, JR., Ince, A., et al.[2016]

Subcutaneous trastuzumab (SQ trastuzumab) has a similar safety profile to intravenous trastuzumab (IV trastuzumab), with adverse event rates ranging from 64% to 97.6% for SQ compared to 94.6% for IV in phase III trials.

SQ trastuzumab offers potential cost savings of $2,090 to $4,600 per 52-week treatment cycle, making it a more economical option, although further research is needed to understand its efficacy in patients with extreme body weights.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab/Hyaluronidase-oysk: A New Option for Patients With HER2-Positive Breast Cancer. Duco, MR., Murdock, JL., Reeves, DJ.[2020]

A 31-year-old woman with common variable immunodeficiency (CVID) successfully switched from intravenous immunoglobulin (IVIg) to subcutaneous immunoglobulin (SCIg) administration facilitated by recombinant human hyaluronidase during her pregnancy, allowing for effective treatment every 3-4 weeks.

The treatment was well tolerated and maintained sufficient immunoglobulin G (IgG) levels for both the mother and her newborn, highlighting the importance of patient preference and medical needs in choosing immunoglobulin administration methods during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case report of pregnancy in a patient with common variable immunodeficiency emphasizing the need for personalized immunoglobulin replacement. Więsik-Szewczyk, E., Jahnz-Różyk, K.[2022]

Subcutaneous immunoglobulin therapy, enhanced with recombinant human hyaluronidase, allows for larger infusion volumes and faster administration rates, making it comparable to intravenous therapy while improving patient comfort.

A phase III clinical trial demonstrated that this enzyme-enhanced subcutaneous method is well tolerated, potentially increasing patient adherence and quality of life compared to traditional intravenous immunoglobulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in gammaglobulin therapy for immunodeficiency: from subcutaneous to intravenous infusions and back again. Wasserman, RL.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04317066

A Study of Pembrolizumab (MK-3475) in Participants With ... The purpose of this study is to evaluate the objective response, safety, and tolerability of pembrolizumab in Japanese participants who have refractory primary ...

2. 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.

3. merckclinicaltrials.com merckclinicaltrials.com/trial/nct06504394/

A Study to Evaluate the Safety and Efficacy of Pembrolizumab ... The primary purpose of the study is to assess the pharmacokinetics (PK) profile of pembrolizumab following subcutaneous (SC) injection of pembrolizumab ...

4. merck.com merck.com/news/mercks-investigational-subcutaneous-pembrolizumab-with-berahyaluronidase-alfa-demonstrates-noninferior-pharmacokinetics-compared-to-intravenous-iv-keytruda-pembrolizumab-in-pivotal/

Merck's Investigational Subcutaneous Pembrolizumab With ... Subcutaneous pembrolizumab administered every six weeks with a median injection time of two minutes, in combination with chemotherapy, shows consistent results.

5. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) Health care professionals may review efficacy data for KEYTRUDA® (pembrolizumab), browse the indications and select the corresponding KEYNOTE trials for ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06504394

NCT06504394 | A Study to Evaluate the Safety and ... A Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) Coformulated With Berahyaluronidase Alfa (MK-3475A) in Participants With Relapsed or ...

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

Safety and tolerability of pembrolizumab in patients with ... These results in heavily pretreated rrPMBCL patients demonstrate that PD-1 blockade with pembrolizumab has a manageable safety profile and promising antitumor ...