Pembrolizumab + Chemotherapy for Non-Small Cell Lung Cancer

Not currently recruiting at 4 trial locations

Overseen By Clinical Trials Hotline

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: Pembrolizumab

Must not be taking: Investigational agents, Systemic steroids

Disqualifiers: EGFR, ALK, ROS1, BRAF, 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

Compensation: Varies

Number of Visits: 5

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a blood test can guide treatment decisions for individuals with advanced non-small cell lung cancer. The study examines whether the blood test can detect early responses to pembrolizumab, an immunotherapy drug, either alone or in combination with chemotherapy. Participants will begin with pembrolizumab, and their blood test results will determine whether they continue with pembrolizumab alone or add chemotherapy. Individuals with stage IV non-small cell lung cancer who have not yet received systemic anti-cancer treatment may be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on systemic steroids or other investigational agents, you may need to stop them before joining the study. It's best to discuss your current medications with the study team.

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

Previous studies have shown pembrolizumab to be safe and effective for treating several types of cancer, including non-small cell lung cancer (NSCLC). The FDA has approved it for this use, indicating it is generally well-tolerated.

When used alone, pembrolizumab has demonstrated long-term safety. Studies also show that combining pembrolizumab with platinum-based chemotherapies like carboplatin and pemetrexed is safe. This combination is a common treatment for NSCLC. Similarly, testing has shown that using pembrolizumab with paclitaxel is safe.

Side effects can occur but are often mild or manageable. Some people might feel tired, nauseous, or notice changes in their appetite. In most cases, these side effects improve over time or with treatment adjustments.

Research on pembrolizumab with different chemotherapies has shown it is generally safe for participants, with the benefits often outweighing the risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for non-small cell lung cancer because they involve pembrolizumab, an immunotherapy drug that helps the body's immune system target and destroy cancer cells more effectively. Unlike traditional chemotherapy, which directly attacks cancer cells and often affects healthy cells too, pembrolizumab works by blocking the PD-1 pathway, allowing immune cells to better recognize and attack cancer cells. Additionally, this study explores combining pembrolizumab with standard chemotherapy drugs like carboplatin, paclitaxel, and pemetrexed, potentially enhancing the overall anti-cancer effect and offering more tailored treatment options based on individual response. This innovative approach aims to improve outcomes and reduce side effects compared to existing therapies.

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

Studies have shown that pembrolizumab, when combined with chemotherapy, extends the lives of patients with advanced non-small cell lung cancer (NSCLC). Specifically, the KEYNOTE-189 and KEYNOTE-407 studies found that about 19% of patients treated with this combination survived for five years. This trial will evaluate pembrolizumab in different treatment arms. In one arm, participants will receive pembrolizumab alone, while in another, they will receive pembrolizumab with doublet chemotherapy, which may include agents like pemetrexed, carboplatin, or paclitaxel. This treatment also resulted in better response rates and longer periods without cancer progression compared to chemotherapy alone. Additionally, real-world studies confirm that the benefits observed in clinical trials also apply in everyday medical practice. These findings suggest that pembrolizumab, either alone or with chemotherapy, may effectively treat NSCLC. ^{2 6 7 8 9}

Who Is on the Research Team?

Julia Rotow, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with stage IV Non-Small Cell Lung Cancer (NSCLC) who haven't had systemic anti-cancer therapy for it. They must have normal organ/marrow function, a PD-L1 tumor score ≥1%, and be able to use contraception. Excluded are those with certain genetic mutations, recent chemo/radiotherapy, uncontrolled illnesses, other investigational drugs, active autoimmune diseases needing high-dose steroids, known allergies to similar drugs, pregnancy/breastfeeding women, HIV/AIDS patients or uncontrolled brain metastases.

Inclusion Criteria

My lung cancer is confirmed to be at stage IV.

Ability to understand and the willingness to sign a written informed consent document.

I haven't had systemic anti-cancer therapy for stage IV NSCLC, but treatments for earlier stages are okay if they were over 6 months ago.

Exclusion Criteria

I have not had chemotherapy or radiotherapy in the last week.

I have stable brain metastases and am not on high-dose steroids.

I do not have any serious illnesses that would stop me from following the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab for the first two cycles, with plasma genotyping to guide adaptive treatment

6 weeks

2 visits (in-person) for plasma draw and treatment

Adaptive Treatment

Based on plasma genotyping results, participants continue with pembrolizumab alone or switch to pembrolizumab with chemotherapy

Up to 12 months

Visits every 3 weeks for treatment and evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• InVision
• Paclitaxel
• Pembrolizumab
• Pemetrexed

Trial Overview The trial is testing if a blood test called InVision can predict early response in NSCLC treated with pembrolizumab alone or combined with chemotherapy (carboplatin plus pemetrexed or paclitaxel). The goal is to see if the blood test results can guide whether to continue pembrolizumab alone or add chemotherapy.

How Is the Trial Designed?

Group I: Pembrolizumab Cycles 1-2 Experimental Treatment 2 Interventions

* For the first two cycles, Pembrolizumab will be administered at a predetermined dose every 3 weeks. * InVision plasma draw will take place at Cycle 1 Day 1 and Cycle 2 Day 1, with return of results to the treating oncologist prior to Cycle 3 Day 1. * At Cycle 3, patients will be re-registered per the inclusion criteria into 3 arms; * PEMBROLIZUMAB Alone * PEMBROLIZUMAB + Doublet Chemotherapy

Group II: Pembrolizumab Alone, Cycle 3+ Experimental Treatment 1 Intervention

\- Following imaging assessment at Cycle 3, participants will continue pembrolizumab alone if the following responses are observed: * Response of Partial Response/Complete Response * Response of Stable Disease with plasma response * Response of Progressive Disease without worsening cancer symptoms AND plasma response

Group III: Pembrolizumab + Doublet Chemotherapy, Cycles 3+ Experimental Treatment 4 Interventions

* Following imaging assessment at Cycle 3, participants will receive pembrolizumab in combination with platinum doublet chemotherapy if they have a response of stable disease without plasma response, OR no plasma response and response of progressive disease without worsening cancer systems. Platinum doublet should be histology-appropriate and will be given on-label, per treating oncologist. * PEMBROLIZUMAB * Chemotherapy multiple agents systemic * PEMETREXED * CARBOPLATIN * PACLITAXEL

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Julia K. Rotow, MD

Lead Sponsor

Trials

1

Recruited

40+

Inivata

Industry Sponsor

Trials

5

Recruited

700+

Published Research Related to This Trial

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 patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

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]

The combination of pemetrexed, platinum, and pembrolizumab shows manageable toxicity, with most severe adverse events occurring early in treatment and resolving within two weeks, indicating a favorable safety profile for long-term use.

While there was a slightly higher incidence of renal toxicity in patients receiving the pembrolizumab combination compared to those on pemetrexed alone, this did not increase with longer treatment durations, supporting the regimen's safety in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of KEYNOTE-189. Garon, EB., Aerts, J., Kim, JS., 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]

Pemetrexed, when combined with cisplatin, significantly improves median survival in patients with malignant pleural mesothelioma, with a median survival of 12.1 months compared to 9.3 months for cisplatin alone, based on a phase III trial involving 448 patients.

The drug works by inhibiting key enzymes involved in DNA synthesis, but it can cause side effects like myelosuppression, neutropenia, and fatigue, necessitating supportive care with folic acid, vitamin B12, and corticosteroids during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summaries: pemetrexed (Alimta). Hazarika, M., White, RM., Johnson, JR., et al.[2022]

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 systematic review and network meta-analysis of first-line treatments for metastatic nonsquamous non-small-cell lung cancer (NSq-NSCLC), the combination of pembrolizumab, pemetrexed, and platinum showed a statistically significant improvement in overall survival compared to various other regimens, with hazard ratios ranging from 0.42 to 0.62.

This combination therapy had a 95.6% probability of being the most effective treatment option for overall survival in patients without known targetable mutations, indicating its strong potential as a first-line treatment for this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. Frederickson, AM., Arndorfer, S., Zhang, I., et al.[2022]

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 the KEYNOTE-189 study, first-line treatment with pembrolizumab combined with pemetrexed-platinum significantly improved overall survival (OS) to a median of 22.0 months compared to 10.7 months for the placebo group, indicating a strong efficacy in treating metastatic nonsquamous non-small-cell lung cancer (NSCLC).

The combination therapy also resulted in a median progression-free survival (PFS) of 9.0 months versus 4.9 months for placebo, with benefits observed regardless of tumor PD-L1 expression or the presence of liver/brain metastases, while maintaining a similar incidence of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. Gadgeel, S., Rodríguez-Abreu, D., Speranza, G., et al.[2021]

Citations

1. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39952082/

Five-year efficacy and safety of pembrolizumab as first-line ... The real-world 5-year survival rate of NSCLC cases with PD-L1 ≥ 50 % treated with first-line pembrolizumab was comparable to that in a clinical trial.

3. nature.com nature.com/articles/s41416-024-02895-1

Real-world evidence for pembrolizumab in non-small cell ... Our nationwide study demonstrated a survival benefit over conventional chemotherapy of a similar magnitude as observed in clinical trials.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925005337

Timing of first pembrolizumab infusion and long-term ... We aimed to evaluate whether the timing of the first pembrolizumab infusion affects outcomes in unresectable non-small cell lung cancer (NSCLC).

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1801005

Pembrolizumab plus Chemotherapy in Metastatic Non– ... The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone ...

6. keytruda.com keytruda.com/

KEYTRUDA® (pembrolizumab) - Official Site TREATS 18 TYPES OF CANCER, INCLUDING CERTAIN EARLY-STAGE AND ADVANCED CANCERS. ONE OF THOSE CANCERS IS EARLY-STAGE NON—SMALL CELL LUNG CANCER (NSCLC).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02142738

NCT02142738 | Study of Pembrolizumab (MK-3475) ... This is a study to assess the efficacy and safety of pembrolizumab (MK-3475/SCH 900475) compared to standard of care (SOC) platinum-based chemotherapies.

8. merck.com merck.com/news/keytruda-pembrolizumab-demonstrates-long-term-survival-benefit-in-certain-patients-with-earlier-or-advanced-stages-of-non-small-cell-lung-cancer-nsclc/

KEYTRUDA® (pembrolizumab) Demonstrates Long-Term ... KEYTRUDA® (pembrolizumab) Demonstrates Long-Term Survival Benefit in Certain Patients With Earlier or Advanced Stages of Non-Small Cell Lung ...

9. keytruda.com keytruda.com/non-small-cell-lung-cancer/treatment-options/advanced-nsclc/

Advanced Non–Small Cell Lung Cancer - Treatment Option KEYTRUDA may be your first treatment for advanced NSCLC, either in combination with chemotherapy or used alone as a chemotherapy-free option.