Pembrolizumab + Chemotherapy + Radiation for Lung Cancer

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active TB, CNS metastases, others

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

Compensation: Varies

Number of Visits: 35

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects, best dose, and best way to give pembrolizumab when given together with paclitaxel, carboplatin, and radiation therapy in treating patients with stage II-IIIB non-small cell lung cancer. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving pembrolizumab together with paclitaxel, carboplatin, and radiation therapy may kill more tumor cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any immunosuppressive therapy, you must stop these at least 7 days before starting the trial treatment.

What data supports the effectiveness of the treatment Pembrolizumab + Chemotherapy + Radiation for Lung Cancer?

Research shows that combining pembrolizumab with chemotherapy and radiation may benefit patients with advanced non-small cell lung cancer, as seen in trials where this combination improved treatment outcomes. Additionally, using paclitaxel and carboplatin with radiation has been effective for locally advanced lung cancer. ^{1 2 3 4 5}

Is the combination of pembrolizumab, chemotherapy, and radiation generally safe for humans?

The combination of pembrolizumab with radiation and chemotherapy has been studied for safety in lung cancer patients. Some studies report that it can cause immune-related side effects, such as pneumonitis (lung inflammation) and immune thrombocytopenia (low platelet count), which can be serious. However, other studies suggest that the combination can be safe with careful monitoring. ^{1 3 6 7 8}

What makes the treatment of pembrolizumab with chemotherapy and radiation unique for lung cancer?

This treatment combines pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with chemotherapy and advanced radiation techniques, offering a potentially more effective approach for patients with advanced lung cancer compared to traditional treatments. ^{1 2 3 9 10}

Research Team

Salma Jabbour, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Eligibility Criteria

This trial is for adults with stage II-IIIB non-small cell lung cancer who haven't had prior treatments that conflict with the study. They must have good organ function, no active infections or autoimmune diseases, not be pregnant or breastfeeding, and agree to use contraception. People with certain medical conditions or those who've received specific treatments recently are excluded.

Inclusion Criteria

My kidney function, measured by creatinine or GFR, is within the normal range.

I agree to use birth control during and for 4 months after the study.

Absolute neutrophil count (ANC) >= 1,500/mcL

Exclusion Criteria

I have another cancer, but it's either being treated or not worsening, except for certain skin cancers or cervical cancer.

You are allergic to pembrolizumab or any of the ingredients in it.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Patients receive paclitaxel and carboplatin intravenously and undergo radiation therapy for 6 weeks

6 weeks

5 visits per week (in-person)

Pembrolizumab Treatment

Patients receive pembrolizumab intravenously every 21 days for up to 18 courses

Up to 54 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

30 days post-treatment, then every 12 weeks for 1 year, every 16 weeks for 1 year, every 6 months for 3 years, and annually thereafter

Treatment Details

Interventions

• 3-Dimensional Conformal Radiation Therapy
• Carboplatin
• Intensity-Modulated Radiation Therapy
• Paclitaxel
• Pembrolizumab

Trial Overview The trial tests pembrolizumab (an antibody therapy) combined with chemotherapy drugs paclitaxel and carboplatin, alongside radiation therapy. It aims to find the safest doses and how well they work together in treating patients by stopping tumor growth and spread.

Participant Groups

Group I: Treatment (paclitaxel, carboplatin, radiation, pembrolizumab) Experimental Treatment 6 Interventions

Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Patients undergo 3D CRT or IMRT QD 5 days a week for 6 weeks. Beginning 2-6 weeks after, 2 weeks before the end, or at the start of chemotherapy and radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.

3-Dimensional Conformal Radiation Therapy is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in European Union as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Canada as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Japan as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in China as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Switzerland as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Merck Sharp & Dohme LLC

Industry 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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Rutgers Cancer Institute of New Jersey

Collaborator

Trials

72

Recruited

22,200+

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a phase 2 study involving 216 patients with stage III non-small cell lung cancer (NSCLC), the combination of pembrolizumab and concurrent chemoradiation therapy (cCRT) showed a high objective response rate of approximately 70.5% in cohort A and 70.6% in cohort B, indicating strong antitumor activity.

The treatment was associated with manageable safety, with grade 3 or higher pneumonitis occurring in 8.0% of cohort A and 6.9% of cohort B, suggesting that while there are risks, the benefits of this treatment approach may outweigh them for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. Jabbour, SK., Lee, KH., Frost, N., et al.[2022]

In a phase I trial involving 38 patients with extensive-stage small cell lung cancer, the combination of pembrolizumab and thoracic radiotherapy was found to be safe, with no dose-limiting toxicities observed in the first 35 days of treatment.

The median progression-free survival was 6.1 months and overall survival was 8.4 months, suggesting that while the safety profile is promising, further studies are needed to fully understand the efficacy of this combined treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Pembrolizumab and Radiation Therapy after Induction Chemotherapy for Extensive-Stage Small Cell Lung Cancer. Welsh, JW., Heymach, JV., Chen, D., et al.[2023]

The combination of carboplatin and dose-dense pemetrexed with involved field radiotherapy is feasible for treating locally advanced and oligometastatic non-small cell lung cancer (NSCLC), as shown in a phase I study with 18 enrolled patients.

Despite some dose-limiting toxicities observed, the treatment resulted in a median survival time of 28.6 months, with 13 out of 16 evaluable patients showing a local regional response, indicating promising efficacy for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. Shen, X., Denittis, A., Werner-Wasik, M., et al.[2021]

A 74-year-old woman with lung adenocarcinoma developed fatal immune thrombocytopenia after receiving pembrolizumab following radiotherapy, highlighting a potential risk of severe immune-related adverse events (irAEs) when combining these treatments.

Flow cytometry analysis showed increased PD-1 and Ki-67 expression in T cells post-radiotherapy, suggesting that radiotherapy may enhance immune activation and contribute to the development of irAEs in patients undergoing anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. Tamanoi, D., Saruwatari, K., Imamura, K., et al.[2022]

The study successfully developed and validated methods for delivering ultra-high doses of radiation (BED10 > 300 Gy) using volumetric modulated arc therapy (VMAT) in a safe manner, achieving high coverage of tumor subvolumes while protecting surrounding organs at risk.

Out of 30 treatment plans evaluated, 12 out of 15 plans using 6FFF beams and 13 out of 15 using 10FFF beams met the primary goal of delivering over 95% of the prescribed dose to the target area, demonstrating the feasibility of this approach for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation treatment planning study to investigate feasibility of delivering Immunotherapy in Combination with Ablative Radiosurgery to Ultra-High DoSes (ICARUS). Rokni, MB., Pointer, KB., George, J., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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]

In a study of 98 patients with advanced non-small-cell lung cancer (NSCLC), those who had previously received radiotherapy experienced significantly longer progression-free survival (4.4 months) and overall survival (10.7 months) when treated with pembrolizumab compared to those without prior radiotherapy.

The safety profile was acceptable, with similar rates of severe pulmonary toxicity between patients who had and had not received thoracic radiotherapy, suggesting that combining radiotherapy with pembrolizumab may be a beneficial treatment strategy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Shaverdian, N., Lisberg, AE., Bornazyan, K., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. [2022]

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

Phase I Trial of Pembrolizumab and Radiation Therapy after Induction Chemotherapy for Extensive-Stage Small Cell Lung Cancer. [2023]

4. China pubmed.ncbi.nlm.nih.gov

[Weekly paclitaxel and carboplatin with concurrent three dimensional conformal radiotherapy for locally advanced non small cell lung cancer]. [2015]

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

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. [2021]

6. Japan pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. [2022]

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

Radiation treatment planning study to investigate feasibility of delivering Immunotherapy in Combination with Ablative Radiosurgery to Ultra-High DoSes (ICARUS). [2021]

8. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. [2022]