Immunotherapy + Chemotherapy for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+848 other locations
Overseen ByJacob M Sands
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: National Cancer Institute (NCI)
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.
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.
567910What 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.
6781011Is 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.
12347Will 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.
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
I haven't needed treatment for an autoimmune disease in the last 2 years.
I have not had a transplant of tissue or an organ from another person.
My lung cancer was surgically removed with clear margins.
I am a woman who can still have children and have not been through menopause for 12 months.
I am not pregnant or breastfeeding.
My cancer has been tested for PD-L1 using specific methods.
I have never had hepatitis B or C.
I have not received initial treatment for my current lung cancer.
I don't have any serious ongoing illnesses or heart problems.
I have never needed steroids for lung inflammation.
I am fully active or can carry out light work.
I am 18 years old or older.
I don't have an active, progressing second cancer that needed treatment in the last 3 years.
Exclusion Criteria
I have a history of cancer.
I have had a condition where lymphocytes are produced in excessive amounts.
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: Arm C (platinum doublet, combination pembrolizumab)Experimental Treatment11 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 Treatment11 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 Control11 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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Baptist Health HamburgLexington, KY
Corewell Health Dearborn HospitalDearborn, MI
Corewell Health Farmington Hills HospitalFarmington Hills, MI
LSU Health Baton Rouge-North ClinicBaton Rouge, LA
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46. [2015]Based on their good activity and minimal toxicity in non-small cell lung cancer and other cancers, we initiated a phase II trial of carboplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with previously untreated stage IIIB and IV non-small cell lung cancer. Among 51 patients treated, the overall response rate was 27.5% (14 partial responses). Seventeen patients had stable disease, while 16 patients experienced disease progression after two cycles of treatment. Apart from myelosuppression, toxicity has been modest, with fewer than 5% of patients experiencing grade 3 or greater nonhematologic toxicity. Objective response and survival rates were modestly improved among patients given the higher of two paclitaxel doses (175 mg/m2 v 135 mg/m2). These data suggest that paclitaxel plus carboplatin warrants further study in metastatic non-small cell lung cancer.
Pemetrexed disodium for the treatment of NSCLC: an update. [2017]Pemetrexed disodium is a multitargeted antifolate cytotoxic chemotherapy agent approved by the U.S. Food and Drug Administration (FDA) initially for the treatment of malignant pleural mesothelioma, and in August 2004 for second-line treatment of non-small cell lung cancer (NSCLC). In September 2008, the FDA also approved pemetrexed and cisplatin as first-line therapy for NSCLC. Pemetrexed is also no longer recommended for treatment of NSCLC with squamous cell carcinoma histology. Pemetrexed is currently being tested in clinical trials as part of second-line combination, first-line, adjuvant and maintenance therapies.
A randomized phase 3 trial comparing pemetrexed/carboplatin and docetaxel/carboplatin as first-line treatment for advanced, nonsquamous non-small cell lung cancer. [2018]This study compared survival without toxicity in patients with advanced, nonsquamous non-small cell lung cancer who were treated with first-line pemetrexed/carboplatin or docetaxel/carboplatin.
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]PRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC).
Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]Platinum-based chemotherapy has long been the first-line treatment of choice for metastatic non-small-cell lung cancer (NSCLC) patients who lack targetable gene mutations. The arrival of checkpoint blockade has led to a vast shift in the treatment landscape of NSCLC. Among NSCLC patients with PD-L1 expression in ≥50% of tumor cells, treatment with pembrolizumab leads to a superior progression-free and overall survival compared to platinum-doublet chemotherapy in the first-line setting. Furthermore, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significant longer progression-free survival and overall survival irrespective to PD-L1 expression. In this review, we focus on the molecular rationale for the combination therapy and the results of completed clinical studies.
Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. [2021]In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous non‒small-cell lung cancer (NSCLC), irrespective of tumor programmed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680).
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
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]Before the approval of first-line immune checkpoint inhibitors, platinum doublets were the standard of care in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. Pemetrexed-platinum combinations are preferred in non-squamous NSCLC. However, there has been no direct comparison to paclitaxel-carboplatin.
Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. [2022]In the phase III KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed-platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) versus placebo plus pemetrexed-platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed-platinum and in patients who completed 35 cycles (∼2 years) of pembrolizumab.
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]Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.
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]For patients with advanced nonsquamous non-small cell lung cancer (NSCLC), immunotherapy or antiangiogenic therapy combined with pemetrexed and cisplatin/carboplatin have both shown significant efficacy at programmed cell death ligand 1 (PD-L1) levels of