Pembrolizumab + Berahyaluronidase for Non-Small Cell Lung Cancer

Recruiting at 89 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Small cell lung cancer, CNS metastases, autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 months

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to treat non-small cell lung cancer (NSCLC) that has spread to other parts of the body. The study compares two forms of pembrolizumab, a cancer treatment: one administered by IV infusion (directly into the vein) and the other as a subcutaneous injection (under the skin) with a helper called berahyaluronidase. Researchers aim to observe how pembrolizumab behaves in the body over time with these two methods. Suitable participants have a confirmed diagnosis of NSCLC that can be measured by doctors and have not received prior systemic therapy for their metastatic condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pembrolizumab, when administered with berahyaluronidase alfa under the skin, is well-tolerated. Studies have found that this method is as effective as the traditional IV method. The under-the-skin method also offers a quick injection time, providing convenience.

Pembrolizumab's safety profile is well-established, as it is already approved for treating several cancers, such as non-small cell lung cancer. This approval indicates that while serious side effects can occur, they are understood and managed.

So far, studies on pembrolizumab with berahyaluronidase alfa have not identified any unexpected safety issues. Ongoing research continues to monitor for any new side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pembrolizumab and Berahyaluronidase alfa for treating non-small cell lung cancer (NSCLC) because it introduces a novel approach. Pembrolizumab is a well-known immunotherapy that enhances the body's immune response against cancer cells, but when paired with Berahyaluronidase alfa, which is administered subcutaneously, it could improve drug absorption and distribution. This combination might allow for more efficient and potentially more effective treatment, setting it apart from the standard care options like chemotherapy and radiation, which often have significant side effects and may not target cancer cells as precisely. The innovative delivery method and the potential for a more targeted action make this treatment combination a promising new option for NSCLC patients.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research shows that pembrolizumab effectively treats advanced non-small cell lung cancer (NSCLC). In this trial, some participants will receive pembrolizumab through an intravenous (IV) drip, while others will receive it as a subcutaneous (SC) injection with berahyaluronidase alfa. Studies have found that the drug's concentration in the body remains similar whether administered as an IV or SC with berahyaluronidase alfa, indicating that the SC injection is as effective as the IV drip. The SC injection is also faster and more convenient, offering a significant advantage for patients. These findings support using pembrolizumab to manage NSCLC that has metastasized. ^{1 2 3 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp and Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with a confirmed diagnosis of non-small cell lung cancer (NSCLC) that has spread to other parts of the body. Participants must have measurable disease as assessed by their local site investigator or radiology.

Inclusion Criteria

Measurable disease as assessed by the local site investigator/radiology

My lung cancer is confirmed by lab tests.

Exclusion Criteria

I have been diagnosed with small cell lung cancer.

I am currently being treated for an infection.

I have had treatment for my advanced lung cancer before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab either as an IV infusion or SC injection for the treatment of metastatic NSCLC

Up to 28 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 32 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Pembrolizumab (+) Berahyaluronidase Alfa

Trial Overview The study compares two ways of administering pembrolizumab, an immunotherapy drug: one group receives it through an IV infusion and another gets a subcutaneous injection combined with Berahyaluronidase alfa.

How Is the Trial Designed?

Group I: Pembrolizumab (+) Berahyaluronidase alfa Experimental Treatment 1 Intervention

Pembrolizumab (+) Berahyaluronidase alfa SC will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course.

Group II: Pembrolizumab Active Control 1 Intervention

"Pembrolizumab by IV Infusion will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course,

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

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

Pembrolizumab, a monoclonal antibody targeting PD-1, has shown significant efficacy in treating advanced non-small-cell lung cancer (NSCLC) across multiple clinical trials, particularly in patients with PD-L1 expression levels of 1% or higher.

The KEYNOTE studies identified specific patient populations that benefit most from pembrolizumab, highlighting the importance of PD-L1 as a companion diagnostic, while future research will explore its role in earlier stages of cancer treatment and in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in lung cancer: current evidence and future perspectives. Palumbo, G., Carillio, G., Manzo, A., et al.[2020]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a study of 72 treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression, pembrolizumab showed an objective response rate of 45.8%, with even higher rates of 70.0% in patients with pre-existing interstitial lung disease (ILD).

Patients with ILD had similar overall survival rates compared to those without ILD, suggesting that pembrolizumab can be safely administered to NSCLC patients with ILD without compromising their prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. Yamaguchi, O., Kaira, K., Shinomiya, S., et al.[2021]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

A 62-year-old patient with advanced non-small-cell lung cancer developed interstitial nephritis after seven cycles of treatment with pembrolizumab, leading to a decline in kidney function and eventual discontinuation of the drug.

Although renal adverse events are rare (reported in less than 3% of patients), this case highlights the importance of monitoring kidney function during pembrolizumab treatment, as early detection of issues like increased serum creatinine levels can aid in management, even if full recovery of kidney function is not guaranteed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interstitial nephritis with pembrolizumab: A case report and review. Peláez Bejarano, A., Montero Pérez, O., Inoriza Rueda, A., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40157574/

the phase III 3475A-D77 trial Conclusions: Overall exposure and trough concentrations of pembrolizumab s.c. 790 mg q6w were noninferior to those of pembrolizumab i.v. 400 mg q6w given with ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00123-1/fulltext

Subcutaneous versus intravenous pembrolizumab, in ... A multi-country time & motion study of subcutaneous vs intravenous pembrolizumab plus chemotherapy in metastatic non-small cell lung cancer.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925004915

Pharmacokinetics and bioavailability of pembrolizumab ... Arm 4 results provided key clinical data supporting the pembrolizumab SC 395 mg Q3W dosing regimen. The immunogenicity of pembrolizumab SC and ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06212752

NCT06212752 | A Study of Subcutaneous (SC) ... This study is to assess the pharmacokinetics (PK) and safety of SC pembrolizumab (+) berahyaluronidase alfa vs intravenous (IV) pembrolizumab, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05722015

NCT05722015 | A Study of Subcutaneous (SC) ... This study is to assess the pharmacokinetics (PK) and safety of SC pembrolizumab formulated with berahyaluronidase alfa (MK-3475A) versus (vs) intravenous (IV) ...