Immunotherapy + Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 880 trial locations

Overseen By Eric C. McGary

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Immunosuppressives

Disqualifiers: Auto-immune disease, Pneumonitis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 18

1210 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding pembrolizumab, an immunotherapy drug, to standard chemotherapy can extend the lives of people with certain types of non-small cell lung cancer after surgery. Pembrolizumab may boost the immune system to fight cancer, while chemotherapy targets and kills cancer cells. Participants will receive different combinations of treatments, including carboplatin, gemcitabine hydrochloride, paclitaxel, and pemetrexed disodium, to determine the most effective approach. This trial is for individuals who have had stage IIA, IIB, IIIA, or IIIB non-small cell lung cancer completely removed by surgery and have not received any prior treatments for this cancer. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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 have an active autoimmune disease that required treatment in the last 2 years, you may not be eligible. 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?

Earlier studies found that combining pembrolizumab with carboplatin and gemcitabine is safe and effective for treating certain cancers. Participants managed this treatment well, experiencing manageable side effects. Another study showed that carboplatin, paclitaxel, and pembrolizumab were safe for patients with non-small cell lung cancer. Research also shows that combining carboplatin and pemetrexed with pembrolizumab is safe, with side effects similar to standard treatments.

The FDA has already approved pembrolizumab for other cancer types, indicating it is generally well-tolerated. This suggests that while side effects can occur, they are usually not severe. Overall, these studies indicate that the treatments tested in the trial are safe for people, based on past research and current approvals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine immunotherapy with chemotherapy to target non-small cell lung cancer effectively. Unlike traditional treatments that rely solely on chemotherapy, this approach uses pembrolizumab, an immunotherapy drug that helps the immune system recognize and attack cancer cells. This combination could enhance the effectiveness of chemotherapy drugs like carboplatin and paclitaxel, potentially leading to better patient outcomes. By integrating immunotherapy, there's hope for longer-lasting responses and improved survival rates, which sets this treatment apart from standard chemotherapy regimens.

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

Research shows that adding pembrolizumab to chemotherapy may help treat non-small cell lung cancer (NSCLC). In this trial, participants in Arm B and Arm C will receive pembrolizumab with a platinum doublet chemotherapy regimen. Studies have found that this combination can significantly increase survival time and lower the chance of the cancer spreading or worsening. For example, one study found that using pembrolizumab with chemotherapy reduced the risk of cancer by 44% compared to chemotherapy alone. Another study confirmed that pembrolizumab works well and is safe when used with different chemotherapy drugs like carboplatin and pemetrexed. Overall, these findings suggest that pembrolizumab could enhance the effectiveness of chemotherapy for treating NSCLC. ^{1 2 4 6 7}

Who Is on the Research Team?

Jacob M Sands

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for adults with stage IIA, IIB, IIIA or IIIB non-small cell lung cancer that's been surgically removed. Participants must have recovered from surgery, not had prior lung cancer treatments, and have no active infections or serious illnesses. They should not be pregnant/nursing and must agree to contraception due to potential risks of the treatment.

Inclusion Criteria

Negative pregnancy test done =< 7 days prior to registration for women of childbearing potential

I haven't needed treatment for an autoimmune disease in the last 2 years.

Your platelet count is at least 100,000 per cubic millimeter.

Exclusion Criteria

You do not live in the United States.

I haven't had any cancer, except for skin cancer, in the last 5 years.

I have a history of cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Initial Therapy

Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles.

12 weeks

4 visits (in-person)

Continuance Therapy

Patients receive pembrolizumab intravenously. Treatment repeats every 21 days for 13 cycles or every 6 weeks for 12 cycles.

Approximately 9-18 months

13-17 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs at 6 weeks, then every 3 months for 2 years, every 6 months for years 2-4, and then annually for up to 10 years.

Up to 10 years

Regular visits as per schedule

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Gemcitabine Hydrochloride
• Paclitaxel
• Pembrolizumab
• Pemetrexed Disodium

Trial Overview The ALCHEMIST trial is testing if adding pembrolizumab (an immunotherapy drug) to standard chemotherapy improves survival in patients who've had surgery for certain stages of non-small cell lung cancer. It explores whether this combination can better help the immune system fight remaining cancer cells.

How Is the Trial Designed?

Group I: Arm C (platinum doublet, combination pembrolizumab) Experimental Treatment 11 Interventions

INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens\* based on the treating physician's choice of each cycle and pembrolizumab IV over 25-40 minutes on day 1 of each cycle or for cycles 1 and 3 (patients enrolled after 10/14/2020). Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Treatment repeats every 21 days for 13 cycles or every 6 weeks for 12 cycles (patients enrolled after 10/14/2020) in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO as clinically indicated during screening and on the trial. Patients may undergo a MRI during screening and as clinically indicated on the trial, as well as CT and blood sample collection throughout the trial.

Group II: Arm B (platinum doublet, sequential pembrolizumab) Experimental Treatment 11 Interventions

INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens\* based on the treating physician's choice of each cycle and pembrolizumab IV over 25-40 minutes on day 1 of each cycle or for cycles 1 and 3 (patients enrolled after 10/14/2020). Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. CONTINUANCE THERAPY: Patients then receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Treatment repeats every 21 days for 13 cycles or every 6 weeks for 12 cycles (patients enrolled after 10/14/2020) in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO as clinically indicated during screening and on the trial. Patients may undergo MRI during screening and as clinically indicated on the trial, as well as CT and blood sample collection throughout the trial.

Group III: Arm A (platinum doublet, observation) Active Control 11 Interventions

INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens based on the treating physician's choice of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. CONTINUANCE THERAPY: Patients then undergo observation. Patients also undergo ECHO as clinically indicated during screening and on the trial. Patients may undergo MRI during screening and as clinically indicated on the trial, as well as CT and blood sample collection throughout the trial. (CLOSED AS OF UPDATE #7)

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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]

In the phase III KEYNOTE-189 study, pembrolizumab combined with pemetrexed and platinum-based chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) in patients with untreated metastatic nonsquamous non-small-cell lung cancer, with a hazard ratio of 0.56 for OS and 0.49 for PFS after a median follow-up of 31 months.

The treatment was associated with a high objective response rate (ORR) of 48.3% compared to 19.9% for the placebo group, and among patients who completed 35 cycles of pembrolizumab, the ORR was even higher at 85.7%, indicating strong efficacy with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Rodríguez-Abreu, D., Powell, SF., Hochmair, MJ., et al.[2022]

In a phase II trial involving 51 patients with untreated stage IIIB and IV non-small cell lung cancer, the combination of carboplatin and paclitaxel showed an overall response rate of 27.5%, indicating some effectiveness in treating this aggressive cancer.

The treatment was generally well-tolerated, with modest toxicity levels; only 5% of patients experienced severe nonhematologic side effects, suggesting that this combination therapy could be a safe option for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. Johnson, DH., Paul, DM., Hande, KR., et al.[2015]

In a study involving 361 patients with advanced nonsquamous non-small-cell lung cancer, the combination of pemetrexed and carboplatin (Pem+Cb) did not show a significant advantage in progression-free survival without grade 4 toxicity compared to paclitaxel, carboplatin, and bevacizumab (Pac+Cb+Bev).

While both treatment regimens were generally well tolerated, Pem+Cb was associated with higher rates of grade 3/4 anemia and thrombocytopenia, whereas Pac+Cb+Bev had more cases of grade 3/4 neutropenia and alopecia, indicating differing toxicity profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. Zinner, RG., Obasaju, CK., Spigel, DR., et al.[2022]

Pemetrexed disodium is an FDA-approved chemotherapy drug effective for treating malignant pleural mesothelioma and non-small cell lung cancer (NSCLC), particularly in combination with cisplatin as a first-line therapy.

Current guidelines indicate that pemetrexed is not recommended for NSCLC with squamous cell carcinoma histology, and it is being explored in various clinical trials for additional treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed disodium for the treatment of NSCLC: an update. Hsu, JY., Wakelee, H.[2017]

Patients with advanced nonsquamous non-small cell lung cancer treated with pemetrexed/carboplatin experienced significantly longer survival without severe toxicity compared to those treated with docetaxel/carboplatin, with a median of 3.2 months versus 0.7 months.

Overall survival rates were similar for both treatment groups, indicating that while pemetrexed/carboplatin is associated with fewer severe side effects, it does not compromise overall survival compared to docetaxel/carboplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase 3 trial comparing pemetrexed/carboplatin and docetaxel/carboplatin as first-line treatment for advanced, nonsquamous non-small cell lung cancer. Rodrigues-Pereira, J., Kim, JH., Magallanes, M., et al.[2018]

In a study involving 180 patients with advanced non-small cell lung cancer (NSCLC), pemetrexed-carboplatin did not show superior efficacy compared to paclitaxel-carboplatin, with similar progression-free survival (PFS) rates and overall survival after a median follow-up of 17 months.

While both treatment regimens had comparable overall toxicities, the paclitaxel-carboplatin group experienced higher rates of alopecia and peripheral neuropathy, indicating a difference in side effects between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer. Yadav, A., Malik, PS., Khurana, S., et al.[2021]

In a study of 114 patients with advanced nonsquamous non-small cell lung cancer (NSCLC) negative for PD-L1, the combination of antiangiogenic therapy (bevacizumab) and chemotherapy resulted in a longer median progression-free survival (PFS) of 9.8 months compared to 6.7 months for those receiving anti-PD-L1 monoclonal antibodies plus chemotherapy.

Overall survival (OS) also favored the antiangiogenic group, although not statistically significant, indicating that bevacizumab plus chemotherapy may be a more effective first-line treatment for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy or antiangiogenic therapy plus chemotherapy as first-line treatment of patients with PD-L1(-) advanced non-squamous non-small cell lung cancer in a Chinese cohort. Xia, R., Li, Y., Yang, L., 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

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Pembrolizumab (MK-3475) plus platinum and gemcitabine as ... Treatment combination of pembrolizumab plus platinum and 5-fluorouracil (PF) has increased the survival of recurrent or metastatic (R/M) ...

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A Study of Pembrolizumab With Carboplatin and ... The main purpose of this study is to see if Pembrolizumab in combination with chemotherapy (carboplatin and gemcitabine) is safe and effective in treating ...

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the phase III 3475A-D77 trial Conclusions: Overall exposure and trough concentrations of pembrolizumab s.c. 790 mg q6w were noninferior to those of pembrolizumab i.v. 400 mg q6w given with ...

5. medrxiv.org medrxiv.org/content/medrxiv/early/2024/12/21/2024.12.20.24317919/DC12/embed/media-12.pdf?download=true

A Phase I/II Study of Pembrolizumab With Gemcitabine in ... (1) Objective: Correlative analysis of outcomes retrospectively compared with tumor PD-. L1 expression, tumor immune score, and immune response ...

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Gemcitabine, Paclitaxel, and Carboplatin for Advanced ... The purpose of this study was to evaluate the combination of gemcitabine (Gemzar), paclitaxel (Taxol), and carboplatin (Paraplatin) in patients with advanced ...

7. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/non-small-cell-lung-cancer

Non-Small Cell Lung Cancer Clinical Trials The purpose of this study is to compare the effectiveness and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin ...