Pembrolizumab + Hyaluronidase for Lymphoma

Recruiting at 27 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

60 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Pembrolizumab + Hyaluronidase for Lymphoma?

Research on similar treatments, like rituximab combined with hyaluronidase for lymphoma, shows that subcutaneous delivery with hyaluronidase can be as effective as traditional methods, offering similar outcomes and improved convenience for patients. ^{1 2 3 4 5}

Is Pembrolizumab + Hyaluronidase generally safe for humans?

While specific safety data for Pembrolizumab + Hyaluronidase in lymphoma is not available, similar formulations with hyaluronidase, like those used with rituximab for lymphoma, have shown comparable safety to their intravenous counterparts, suggesting it may be generally safe. ^{2 4 6 7 8}

What makes the drug Pembrolizumab + Hyaluronidase unique for treating lymphoma?

Pembrolizumab + Hyaluronidase is unique because it combines an immune-boosting drug (Pembrolizumab) with an enzyme (Hyaluronidase) that allows for subcutaneous (under the skin) administration, potentially offering more convenience compared to traditional intravenous treatments. ^{1 4 6 9 10}

What is the purpose of this trial?

The primary purpose of the study is to assess the pharmacokinetics (PK) profile of pembrolizumab following subcutaneous (SC) injection of pembrolizumab coformulated with hyaluronidase, and to evaluate the objective response rate (ORR) of pembrolizumab (+) berahyaluronidase alfa SC in adult participants with Relapsed or Refractory Classical Hodgkin Lymphoma (rrcHL) or Relapsed or Refractory Primary Mediastinal Large B-cell Lymphoma (rrPMBCL). There is no formal hypothesis to be tested for this study.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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 am currently being treated for an infection.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

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

2. United States 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. [2022]

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

A case report of pregnancy in a patient with common variable immunodeficiency emphasizing the need for personalized immunoglobulin replacement. [2022]

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

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

6. England 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. [2021]

7. United States 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. [2023]

8. England 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. [2016]

9. England 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. [2023]

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

Trastuzumab/Hyaluronidase-oysk: A New Option for Patients With HER2-Positive Breast Cancer. [2020]