Immunotherapy + Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 851 trial locations

Overseen By Eric C. McGary

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Steroids, Immunosuppressives

Disqualifiers: Auto-immune disease, Pneumonitis, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase III ALCHEMIST trial tests the addition of pembrolizumab to usual chemotherapy for the treatment of stage IIA, IIB, IIIA or IIIB non-small cell lung cancer that has been removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as cisplatin, pemetrexed, carboplatin, gemcitabine hydrochloride, and paclitaxel, 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. Giving pembrolizumab with usual chemotherapy may help increase survival times in patients with stage IIA, IIB, IIIA or IIIB non-small cell lung cancer.

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.

What data supports the effectiveness of the drug combination of immunotherapy and chemotherapy for non-small cell lung cancer?

Research shows that combining pembrolizumab (an immunotherapy drug) with chemotherapy drugs like pemetrexed and carboplatin significantly improves survival rates in patients with advanced non-small cell lung cancer. This combination has been shown to help patients live longer and delay the progression of the disease, regardless of certain tumor characteristics. ^{1 2 3 4 5}

Is the combination of immunotherapy and chemotherapy safe for treating non-small cell lung cancer?

The combination of immunotherapy and chemotherapy, including drugs like pembrolizumab, carboplatin, paclitaxel, and pemetrexed, has been studied in clinical trials for non-small cell lung cancer. These studies generally show that the treatments have manageable safety profiles, with some patients experiencing mild to moderate side effects. Serious side effects are less common, but they can occur, so it's important to discuss potential risks with your doctor. ^{1 6 7 8 9}

What makes the combination of immunotherapy and chemotherapy unique for treating non-small cell lung cancer?

This treatment combines pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with chemotherapy drugs like carboplatin and pemetrexed, which kill cancer cells directly. This combination has shown improved survival rates compared to chemotherapy alone, making it a more effective first-line treatment for advanced non-small cell lung cancer. ^{1 2 5 10 11}

Research Team

Jacob M Sands

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Carboplatin (Alkylating agents)
• Gemcitabine Hydrochloride (Anti-tumor antibiotic)
• Paclitaxel (Anti-tumor antibiotic)
• Pembrolizumab (Monoclonal Antibodies)
• Pemetrexed Disodium (Anti-tumor antibiotic)

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.

Participant Groups

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 Canada for the following indications:

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+

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 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 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 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]

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]

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]

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]

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. 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]

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

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]

4. England 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. [2022]

5. United States 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. [2021]

6. United States 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. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Pemetrexed disodium for the treatment of NSCLC: an update. [2017]

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

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. [2015]

9. United States 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. [2018]

10. Switzerland 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. [2021]

11. United States 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. [2023]