Pembrolizumab SC vs IV for Lung Cancer

Recruiting at 125 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Active infection, Autoimmune disease, HIV, 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

Compensation: Varies

Number of Visits: 1

Duration: Up to 2 years

531 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. However, if you are on certain treatments like systemic steroids or other immunosuppressive therapies, you may need to stop them 7 days before starting the trial.

What data supports the effectiveness of the drug combination used in the Pembrolizumab SC vs IV for Lung Cancer trial?

Research shows that using nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with carboplatin improves response rates in patients with advanced non-small cell lung cancer (NSCLC) compared to traditional paclitaxel. This combination is effective as a first-line treatment, particularly in patients with squamous NSCLC, where it showed a higher overall response rate. ^{1 2 3 4 5}

Is the treatment of nab-paclitaxel plus platinum compounds safe for lung cancer patients?

Research shows that nab-paclitaxel combined with platinum compounds like cisplatin or carboplatin has been studied for safety in lung cancer patients. The studies found that this combination has acceptable safety levels, meaning it is generally safe for use in humans with advanced non-small-cell lung cancer. ^{2 3 5 6 7}

What makes the drug Pembrolizumab SC vs IV for lung cancer unique?

This treatment is unique because it compares two forms of administering pembrolizumab, a drug that helps the immune system fight cancer, either through subcutaneous (under the skin) or intravenous (into a vein) routes, potentially offering more flexibility and convenience for patients. ^{2 4 8 9 10}

What is the purpose of this trial?

This trial is testing a new way to give the cancer drug pembrolizumab as an injection under the skin for people with advanced lung cancer. The goal is to see if this method works as well as the traditional IV method. The study will also check if it is safe and effective when used with standard chemotherapy.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with Stage IV squamous or nonsquamous NSCLC who haven't had systemic treatment for metastatic disease. They must have good organ function, an ECOG score of 0 or 1, and agree to use contraception. Exclusions include severe drug hypersensitivity, recent investigational drug use, certain psychiatric disorders, active infections requiring therapy, specific lung conditions like pneumonitis, other active cancers within the last 3 years, known brain metastases unless treated under certain conditions, HIV/Hepatitis B/C infections.

Inclusion Criteria

I can provide a sample of my tumor for PD-L1 testing.

You have a measurable disease according to specific medical assessment guidelines.

My organs are functioning well.

Exclusion Criteria

Has severe hypersensitivity to study intervention and/or any of its excipients

I have another cancer that is getting worse or was treated in the last 3 years.

I've had lung radiation of more than 30 Gray in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab (SC or IV) with platinum doublet chemotherapy for up to 35 cycles (approximately 2 years)

Up to 2 years

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Second Course Treatment (optional)

Participants may receive a second course of pembrolizumab for up to 1 additional year if they experience disease progression after the first course

Up to 1 year

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Nab-Paclitaxel
• Paclitaxel
• Pembrolizumab IV
• Pembrolizumab SC
• Pemetrexed

Trial Overview The study tests pembrolizumab administered subcutaneously versus intravenously in combination with standard chemotherapy (Paclitaxel/Nab-Paclitaxel/Carboplatin/Cisplatin/Pemetrexed) as first-line treatment for metastatic NSCLC. It aims to compare the safety and effectiveness between the two methods of pembrolizumab administration.

Participant Groups

Group I: Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Experimental Treatment 6 Interventions

Participants receive pembrolizumab subcutaneous (SC) administration on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to \~2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for squamous non-small cell lung cancer (NSCLC); PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for non-squamous NSCLC.

Group II: Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy Active Control 6 Interventions

Participants receive pembrolizumab intravenous (IV) administration on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to \~2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for squamous non-small cell lung cancer (NSCLC); PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for non-squamous NSCLC.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

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

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. 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 a study of 40 patients with stage III/IV squamous non-small-cell lung cancer, the combination of nab-paclitaxel and a platinum agent (cisplatin or carboplatin) resulted in a high overall response rate of 62.5% and a disease control rate of 92.5%, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse effects being mild to moderate (grade 1 to 2), including myelosuppression and gastrointestinal issues, suggesting that nab-paclitaxel combined with platinum agents is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. Fang, Y., Wang, L., Xia, GH., et al.[2022]

In a phase III trial involving 1,052 patients with advanced non-small-cell lung cancer, nab-paclitaxel plus carboplatin showed a significantly higher overall response rate (33%) compared to solvent-based paclitaxel plus carboplatin (25%), indicating greater efficacy in treatment.

Nab-paclitaxel was associated with fewer severe side effects, such as neuropathy and neutropenia, compared to solvent-based paclitaxel, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. Socinski, MA., Bondarenko, I., Karaseva, NA., et al.[2022]

Nab-paclitaxel significantly improves overall response (OR) and partial response (PR) rates in advanced non-small cell lung cancer (NSCLC), especially in squamous cell carcinoma and as a second-line treatment, based on a meta-analysis of 35 studies involving various trial designs.

While nab-paclitaxel shows marginal improvements in overall survival (OS) and progression-free survival (PFS), the evidence regarding its safety profile and reduction of adverse events remains inconclusive, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials and observational studies. Suwannasom, N., Sriaksorn, N., Thepmalee, C., et al.[2023]

A phase 3 study (J-AXEL) is underway to compare the efficacy and safety of nab-paclitaxel to docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC), involving randomization of patients to receive either treatment until disease progression or unacceptable toxicity.

The primary goal of the study is to demonstrate that nab-paclitaxel is noninferior to docetaxel in terms of overall survival, which could establish nab-paclitaxel as a new treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Rationale and Design for J-AXEL: A Randomized Phase 3 Study Comparing Nab-Paclitaxel With Docetaxel in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. Yoneshima, Y., Morita, S., Ando, M., et al.[2018]

In a trial involving 84 patients with advanced non-small-cell lung cancer, the efficacy of weekly nab-paclitaxel plus cisplatin was found to be similar to that of gemcitabine plus cisplatin, with median progression-free survival of 4.8 months for nab-TP and 5.2 months for GP.

Nab-paclitaxel showed improved overall survival in patients with EGFR mutations (26.7 months) and those with a performance status of 0 (23.5 months) compared to gemcitabine, indicating potential benefits in specific patient subgroups while maintaining comparable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer: A phase II open-label clinical study. Qin, S., Yu, H., Wu, X., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

This study is the first to evaluate the combination of necitumumab with pembrolizumab and platinum-based chemotherapy in patients with untreated squamous cell lung cancer (SqCLC), aiming to enhance tumor immunity and therapeutic effects.

The trial will assess safety and efficacy, with 42 patients enrolled in phase II to determine the overall response rate and other important outcomes like progression-free survival and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/II Study of Necitumumab Plus Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non-Small Cell Lung Cancer Study: (NEJ048A/NEXUS). Miyanaga, A., Asahina, H., Watanabe, S., et al.[2023]

In a phase II study involving 71 chemotherapy-naïve patients with squamous cell carcinoma of the lung, the overall response rate for carboplatin plus weekly albumin-bound paclitaxel (CnP) was 47%, which is comparable to 43% for cisplatin plus gemcitabine (CG).

While both treatment regimens showed similar efficacy, they differed in toxicity profiles: the CG arm experienced more hematologic toxicities, while the CnP arm had higher rates of anemia and sensory neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of carboplatin + nab-paclitaxel versus cisplatin + gemcitabine for chemotherapy-naïve squamous cell carcinoma: North Japan lung cancer study group 1302. Kawashima, Y., Harada, T., Fujita, Y., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

The efficacy of carboplatin plus nanoparticle albumin-bound paclitaxel after cisplatin plus pemetrexed in non-squamous non-small-cell lung cancer patients. [2020]

2. Thailand pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. [2022]

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

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. [2022]

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

Clinical roundtable monograph: Recent advances in taxanes for the first-line treatment of advanced non-small cell lung cancer. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials and observational studies. [2023]

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

Treatment Rationale and Design for J-AXEL: A Randomized Phase 3 Study Comparing Nab-Paclitaxel With Docetaxel in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. [2018]

7. China pubmed.ncbi.nlm.nih.gov

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer: A phase II open-label clinical study. [2022]

8. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]

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

A Phase I/II Study of Necitumumab Plus Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non-Small Cell Lung Cancer Study: (NEJ048A/NEXUS). [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of carboplatin + nab-paclitaxel versus cisplatin + gemcitabine for chemotherapy-naïve squamous cell carcinoma: North Japan lung cancer study group 1302. [2022]