Pembrolizumab + Chemotherapy for Lung Cancer

Recruiting at 6 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

Trial Summary

What is the purpose of this trial?

Researchers are investigating new treatments for untreated advanced non-small cell lung cancer (NSCLC), which is the most common form of lung cancer and lung cancer that has spread beyond surgical removal. Standard treatments include immunotherapy, such as pembrolizumab, and chemotherapy. This study aims to determine the effectiveness of adding other treatments, including the human epidermal growth factor receptor 3-directed antibody-drug conjugate (HER3-DXd) patritumab deruxtecan, to pembrolizumab, with or without chemotherapy. The primary goals are to assess safety and efficacy of the treatments.

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.

What data supports the effectiveness of the drug combination of Pembrolizumab, Carboplatin, Paclitaxel, and Pemetrexed for lung cancer?

Research shows that Pembrolizumab, when combined with chemotherapy, can improve survival rates in patients with advanced non-small cell lung cancer. In one study, patients receiving this combination had a 12-month survival rate of 69.2%, compared to 49.4% for those receiving chemotherapy alone. ^{1 2 3 4 5}

Is the combination of pembrolizumab and chemotherapy safe for lung cancer patients?

Pembrolizumab, when used alone, has been shown to be generally safe for patients with advanced non-small cell lung cancer (NSCLC). Ongoing studies are exploring its safety when combined with other treatments, including chemotherapy, for lung cancer and other conditions. ^{2 6 7 8 9}

How is the drug pembrolizumab plus chemotherapy different from other treatments for lung cancer?

Pembrolizumab, when combined with chemotherapy, enhances the immune system's ability to fight cancer by targeting a specific protein (PD-1) on immune cells, leading to improved survival rates in patients with advanced non-small cell lung cancer compared to chemotherapy alone. ^{4 10 11 12 13}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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.

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

I have active brain metastases or cancer in my brain's lining.

Timeline

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

Treatment Details

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.

Participant Groups

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 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

Findings from Research

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]

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]

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]

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]

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 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]

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 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]

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 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 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]

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]

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]

References

1. England 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. [2022]

2. England 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. [2022]

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

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]

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

Combo Therapy for Lung Cancer Extends Survival. [2019]

5. India pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of nonsmall cell lung cancer: Current status and future directions. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of pembrolizumab monotherapy in patients with locally advanced or metastatic non-small-cell lung cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab. [2022]

8. Singapore 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. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

11. England 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. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC. [2022]

13. Switzerland 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. [2022]