Pembrolizumab + Chemotherapy for Lung Cancer

Recruiting at 39 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Antiarrhythmics, Topoisomerase inhibitors

Disqualifiers: Small cell lung cancer, Severe pulmonary compromise, Active CNS metastases, 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

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with advanced non-small cell lung cancer (NSCLC) that remains untreated. Researchers aim to determine if adding a drug called patritumab deruxtecan to the standard treatment of pembrolizumab (an immunotherapy drug), with or without chemotherapy, is safe and effective. It targets those whose lung cancer has spread and cannot be surgically removed. Individuals diagnosed with Stage IV NSCLC who have not received prior treatment for their metastatic lung cancer may be suitable candidates for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions an 'inadequate washout period' from prior therapy as an exclusion criterion, suggesting that some medications might need to be stopped before participating. It's best to discuss your specific medications with the trial team.

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

Research has shown that pembrolizumab, a common treatment for lung cancer, is usually well-tolerated by patients. It is often used in standard treatments for non-small cell lung cancer (NSCLC) and has a good safety record. Some patients might experience side effects like tiredness, nausea, or skin rash, but these are generally manageable.

For the new treatment combining pembrolizumab with HER3-DXd (patritumab deruxtecan), studies in patients with various types of lung cancer have reported similar results. This combination treatment appears safe, with side effects similar to those of other treatments.

Although complete data is not yet available, the trial's Phase 2 status suggests that earlier tests (Phase 1) did not reveal major safety issues. Phase 2 trials further assess safety and begin evaluating treatment efficacy. This phase includes more participants, which helps identify any rare side effects.

Overall, while both treatments are still under study, current data suggests they are generally well-tolerated. Participants should discuss any concerns with their healthcare providers to receive tailored advice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they combine pembrolizumab with innovative approaches. Pembrolizumab, an immune checkpoint inhibitor, helps the immune system target cancer cells more effectively. The study also explores the combination of pembrolizumab with HER3-DXd, which is an antibody-drug conjugate targeting the HER3 protein often overexpressed in cancers, offering a novel mechanism of action. Additionally, combining pembrolizumab with standard chemotherapy regimens may enhance the treatment's effectiveness against various types of non-small cell lung cancer (NSCLC) by attacking the cancer on multiple fronts. These combinations hold the potential to improve outcomes compared to current treatments like chemotherapy alone.

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

Studies have shown that pembrolizumab, a type of immunotherapy, effectively treats advanced non-small cell lung cancer (NSCLC) by helping the immune system find and attack cancer cells. In this trial, some participants will receive pembrolizumab combined with HER3-DXd, a drug that targets and kills cancer cells. Research suggests that this combination may lead to improved responses compared to pembrolizumab alone. The study aims to determine if this combination can enhance the body's ability to fight lung cancer. ^{1 2 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 Stage IV NSCLC, who are in good physical condition (ECOG 0 or 1) and have a confirmed diagnosis. Participants can be HIV-positive if their virus is well controlled on ART, and those with hepatitis B must be on antiviral therapy with an undetectable viral load.

Inclusion Criteria

My HIV is well controlled with antiretroviral therapy.

My lung cancer is confirmed to be stage IV NSCLC.

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

Exclusion Criteria

I had a heart or leg artery bypass surgery in the last 6 months.

Has severe hypersensitivity to any of the study interventions and/or any of their excipients

I have not had a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab with or without chemotherapy, and potentially HER3-DXd, for up to 35 cycles (~2 years)

Up to 2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab
• Pemetrexed

Trial Overview

The study tests the effectiveness of adding HER3-DXd to pembrolizumab, with or without chemotherapy drugs like Paclitaxel, Pemetrexed, Nab-paclitaxel, and Carboplatin in treating advanced NSCLC. It aims to assess safety and how well these combinations work.

How Is the Trial Designed?

Group I: Pembrolizumab and HER3-DXd Experimental Treatment 2 Interventions

Pembrolizumab will be administered as a 200mg IV infusion on Day 1 Q3W for up to 35 cycles (\~ 2 years). HER3-Dxd will be administered as 5.6mg/kg IV infusion on Day 1 Q3W until discontinuation criteria is met.

Group II: Pembrolizumab and Chemotherapy Active Control 5 Interventions

Pembrolizumab will be administered as a 200mg IV infusion on Day 1 of every three weeks (Q3W) for up to 35 cycles (\~ 2 years). The doublet platinum-based chemotherapy treatments used in this substudy are standard-of care regimens for squamous (paclitaxel/Nab-paclitaxel and carboplatin) and nonsquamous (pemetrexed and carboplatin) NSCLC. Pemetrexed is administered as a 500mg/m\^2 IV infusion Q3W until discontinuation criterion is met. Nab-paclitaxel will be administered as a 100mg/m\^2 IV infusion on Days 1, 8, and 15 Q3W for up to 4 cycles. Paclitaxel will be administered as a 200 mg/m\^2 IV infusion on Day 1 Q3W for up to 4 cycles. Carboplatin will be administered as an IV infusion area under the time x concentration curve (AUC) for 4 cycles as per local practice and labels. The dose will be AUC5 or 6 mg/mL•min Q3W and will not exceed 900mg.

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

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Published Research Related to This Trial

In a clinical trial, the combination of the PD-1 inhibitor pembrolizumab with chemotherapy showed a significant improvement in overall survival for patients with newly diagnosed advanced non-squamous non-small cell lung cancer, with a 12-month survival rate of 69.2%.

This survival rate was notably higher compared to the 49.4% survival rate in patients who received chemotherapy alone, indicating that pembrolizumab may enhance the effectiveness of standard chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combo Therapy for Lung Cancer Extends Survival. [2019]

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 1 study involving Japanese patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab combined with chemotherapy demonstrated a feasible safety profile, with only one dose-limiting toxicity reported in part B and two in part C, indicating that this treatment can be safely administered.

The overall response rates were promising, with 73% in the nonsquamous group and 50% in the squamous group, showing significant antitumor activity regardless of PD-L1 status, which aligns with findings from international trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC. Kurata, T., Nakagawa, K., Satouchi, M., et al.[2022]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

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 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]

In a study of 62 patients with advanced non-small-cell lung cancer, pembrolizumab monotherapy showed a median progression-free survival of 7.7 months for first-line treatment, indicating its effectiveness in real-world clinical practice.

The treatment was generally well-tolerated, with 64.51% of patients experiencing adverse events, but only 9.38% of these were severe (grade 3), suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of pembrolizumab monotherapy in patients with locally advanced or metastatic non-small-cell lung cancer. Tamayo-Bermejo, R., Del Rio-Valencia, JC., Mora-Rodriguez, B., et al.[2022]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved quality of life (QOL) compared to chemotherapy, with a notable increase in the global health status score by 6.9 points versus a decrease of 0.9 points for chemotherapy.

Patients treated with pembrolizumab experienced a longer time to deterioration in symptoms like cough and chest pain, with 31% showing deterioration compared to 39% in the chemotherapy group, indicating that pembrolizumab may be a preferable first-line treatment for patients with PD-L1-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Brahmer, JR., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

In a study involving 1034 patients with previously treated, PD-L1-positive advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival compared to docetaxel, with median survival times of 12.7 months for pembrolizumab 10 mg/kg versus 8.5 months for docetaxel.

Pembrolizumab also demonstrated a favorable safety profile, with fewer grade 3-5 treatment-related adverse events (13% for 2 mg/kg and 16% for 10 mg/kg) compared to docetaxel (35%), making it a promising treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Herbst, RS., Baas, P., Kim, DW., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, is effective as a first-line treatment for advanced nonsmall cell lung cancer (NSCLC) in patients with high PD-L1 expression (≥50%) and as a second-line option for those with lower PD-L1 expression (≥1%).

When combined with standard chemotherapy, pembrolizumab has demonstrated superior clinical outcomes compared to chemotherapy alone in patients with advanced NSCLC without targetable mutations, regardless of their PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of nonsmall cell lung cancer: Current status and future directions. Qin, Q., Li, B.[2020]

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]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

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