Pembrolizumab + Chemotherapy for Non-Small Cell Lung Cancer

Overseen By Megan Baumgart

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Rochester

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune, Cardiovascular, Renal, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

28 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to understand if treatment with one chemotherapy medication combined with immune therapy (pembrolizumab) is tolerable and effective for patients with lung cancer and performance status of 2 (PS2), which means you have limitations in carrying out certain activities or spend up to half of your day resting.

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on immunosuppressive medications, including high doses of steroids, during the study.

What data supports the effectiveness of the drug combination of Pembrolizumab and Chemotherapy for Non-Small Cell Lung Cancer?

Research shows that nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has shown promising activity and acceptable safety in treating advanced non-small cell lung cancer (NSCLC). Additionally, combining pemetrexed and nab-paclitaxel has been evaluated for safety and effectiveness, suggesting potential benefits for NSCLC patients. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Chemotherapy safe for humans?

The safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has been evaluated in several studies for non-small cell lung cancer, showing acceptable safety and avoiding some toxicities associated with other formulations. These studies suggest that nab-paclitaxel is generally safe for use in humans. ^{1 2 3 4 6}

How is the drug combination of Pembrolizumab, Nab-paclitaxel, and Pemetrexed unique for treating non-small cell lung cancer?

This drug combination is unique because it combines immunotherapy (Pembrolizumab) with chemotherapy agents (Nab-paclitaxel and Pemetrexed) to enhance the immune system's ability to fight cancer while also directly targeting cancer cells, potentially improving survival rates compared to chemotherapy alone. ^{1 7 8 9 10}

Research Team

Megan Baumgart

Principal Investigator

University of Rochester

Eligibility Criteria

This trial is for adults over 18 with advanced non-small cell lung cancer and an ECOG performance status of 2, meaning limited activity or significant rest needed. Eligible patients have specific blood count levels, can't be on high-dose steroids or other trials, and must not have severe untreated brain metastases or certain autoimmune diseases.

Inclusion Criteria

- AST and ALT ≤ 2.5 x ULN

Histologically confirmed non-small cell lung cancer

ECOG PS 2

Exclusion Criteria

Patients with history of autoimmune conditions with the following exceptions, which are allowed: alopecia, vitiligo, rheumatoid arthritis, psoriasis/psoriatic arthritis, Hashimoto's thyroiditis

Patients on immunosuppressive medication, including steroids (if doses exceed equivalent of prednisone 10 mg daily). Short courses of steroids which are discontinued prior to start of treatment are acceptable.

The patient must not be on any clinical trials involving other experimental therapies during study treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab and chemotherapy every 21 days. For non-squamous, pembrolizumab 200 mg and Pemetrexed 500 mg/m2 on day 1 of a 21-day cycle. For others, pembrolizumab 200 mg and Nab-paclitaxel 100 mg/m2 on days 1 and 8 of a 21-day cycle for 4 cycles, followed by pembrolizumab alone.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Treatment Details

Interventions

• Nab-paclitaxel
• Pembrolizumab
• Pemetrexed

Trial Overview The study tests the combination of Pembrolizumab (an immune therapy) with a single chemotherapy agent (Pemetrexed or Nab-paclitaxel) in patients who are unsuitable for standard treatments. It aims to assess the tolerability and effectiveness of this regimen in those with reduced physical function.

Participant Groups

Group I: Experimental 2: pembrolizumab and Nab-paclitaxel Experimental Treatment 2 Interventions

Treatment includes administration of pembrolizumab and chemotherapy, which are administered every 21 days Pembrolizumab 200 mg and Nab-paclitaxel 100 mg/m2 days 1,8 of 21 day cycle x 4 cycles followed by pembrolizumab alone

Group II: Experimental 1: pembrolizumab and Pemetrexed Experimental Treatment 2 Interventions

Treatment includes administration of pembrolizumab and chemotherapy, which are administered every 21 days Pembrolizumab 200 mg and Pemetrexed 500 mg/m2 day 1 of 21 day cycle (for non-squamous only)

Nab-paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Abraxane for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Adenocarcinoma of the pancreas

Approved in European Union as Abraxane for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Adenocarcinoma of the pancreas

Approved in Canada as Abraxane for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Adenocarcinoma of the pancreas

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Findings from Research

The combination of pemetrexed and nab-paclitaxel was found to be feasible and well tolerated in patients with advanced non-small cell lung cancer (NSCLC), with a recommended phase II dose established at pemetrexed 500 mg/m² and nab-paclitaxel 260 mg/m².

In a phase II trial involving 37 patients, the treatment showed a response rate of 14% and a disease control rate of 46%, with a median overall survival of 8.8 months, indicating some efficacy in second and third-line therapy despite the early closure of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. Ho, C., Davies, AM., Sangha, RS., et al.[2023]

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]

In a study of 101 patients with advanced non-small-cell lung cancer (NSCLC), nab-paclitaxel demonstrated an overall response rate of 32.9% and a disease control rate of 89.9%, indicating its efficacy in treating this condition.

The treatment was associated with manageable side effects, with the most common severe adverse events being peripheral neuropathy (5.9%) and leukopenia (5.0%), suggesting that nab-paclitaxel is a viable option for patients despite some risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the clinical outcome of nab-paclitaxel in Chinese patients with advanced non-small-cell lung cancer. Zeng, J., Yin, J., Yuan, D., et al.[2022]

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]

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, an immune checkpoint inhibitor used for treating non-small cell lung carcinoma, has been associated with improved overall survival compared to traditional chemotherapy, but it can also lead to serious side effects.

This case report highlights a rare but critical complication: a 62-year-old man experienced small intestinal perforation due to metastatic lung adenocarcinoma after receiving pembrolizumab, emphasizing the need for careful monitoring of patients for potential autoimmune side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. Sato, S., Senmaru, N., Ishido, K., et al.[2020]

Pembrolizumab, an immunotherapy for advanced non-small-cell lung cancer (NSCLC), significantly improves progression-free and overall survival compared to traditional chemotherapy, with fewer side effects, particularly in patients with high PD-L1 expression (≥50%).

In combination with pemetrexed and carboplatin, pembrolizumab also enhances treatment effectiveness and maintains manageable toxicity, leading to a shift in first-line treatment strategies for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. Reck, M.[2018]

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]

References

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

Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. [2023]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Assessing the clinical outcome of nab-paclitaxel in Chinese patients with advanced non-small-cell lung cancer. [2022]

4. 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]

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

Nanoparticle Albumin-bound Paclitaxel Plus Carboplatin Induction Followed by Nanoparticle Albumin-bound Paclitaxel Maintenance in Squamous Non-Small-cell Lung Cancer (ABOUND.sqm): A Phase III Randomized Clinical Trial. [2021]

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

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy as second-line therapy of cytotoxic anticancer drugs in patients with advanced non-small cell lung cancer. [2022]

7. 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]

8. Germany pubmed.ncbi.nlm.nih.gov

Perforation of small intestinal metastasis of lung adenocarcinoma treated with pembrolizumab: a case report. [2020]

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

Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. [2018]

10. 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]