The ALCHEMIST Lung Cancer Trials

The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials, or ALCHEMIST, are a group of randomized clinical trials for patients with early-stage non-small cell lung cancer (NSCLC) whose tumors have been completely removed by surgery. For patients with early-stage NSCLC, there is a 50% chance that the cancer will come back, even after patients receive standard treatment. The ALCHEMIST trials test to see if adding targeted therapy based on patients' tumor genetics will help prevent the cancer from returning and therefore increase the number of people who may live longer. The targeted therapy would be in addition to and after the patient completes the usual standard of care treatment.

The ALCHEMIST trials are testing therapies that target two types of genetic changes that are thought to drive lung cancer growth: mutations in the EGFR gene and a rearrangement of the ALK gene. These changes are relatively rare: EGFR mutations are found in about 10% to 15%, and ALK rearrangement in 5% to 6%, of lung cancer patients. The FDA has already approved the use of erlotinib (Tarceva®) for patients with advanced lung cancer who test positive for an EGFR mutation and crizotinib (Xalkori®) for patients with advanced lung cancer who test positive for the ALK rearrangement. ALCHEMIST is testing whether these drugs will also help patients with early-stage NSCLC who test positive for ALK or EGFRchanges in their tumor.

Patients whose tumors do not have the EGFR or ALK gene change may be able to enroll in a third ALCHEMIST treatment trial that is comparing the immunotherapy drug nivolumab(Opdivo®) with observation. This immunotherapy drug may help patients’ immune system prevent cancer from coming back by blocking a protein called PD-L1.

Before enrolling in any ALCHEMIST treatment trial, patients must first complete their standard treatment regimen as prescribed by their doctors (post-surgical chemotherapy with or without radiation therapy). Approximately 6,000-8,000 patients will have their tumor tissue tested for the ALCHEMIST trials.

ALCHEMIST - Screening Trial [A151216]:

To determine which trial is best for patients, doctors will screen patients by examining a small sample of their tumor and testing it for the presence of EGFR mutations and the ALKrearrangement. Patients who have either of these alterations will then be referred to one of two treatment trials that are testing the drugs erlotinib (for EGFR mutations) or crizotinib (for the ALK rearrangement) versus placebo. Patients who are negative for both EGFR and ALK alterations will be referred to the immunotherapy trial testing nivolumab. All patients screened on A151216 will be monitored for 5 years. See the patient handout for the ALCHEMIST Screening Trial.

The screening trial is answering the following research questions:

How many early-stage NSCLC patients will have an EGFR or ALK gene alteration and thus have the possibility to participate in one of the ALCHEMIST targeted treatment clinical trials?
More broadly, what is the genomic landscape of resected lung cancer and how do gene alterations affect clinical outcome?

ALCHEMIST - EGFR Treatment Trial [A081105]:

Mutations in EGFR are found in about 10% to 15% of non-Asian patients with NSCLC and up to 50% of Asian patients. Patients whose tumors test positive for an EGFR mutation will be referred to the ALCHEMIST EGFR treatment trial. In this trial, eligible patients will be randomly assigned to take the drug erlotinib or a matching placebo pill for up to 2 years, or until they experience unacceptable toxicity or a recurrence of their cancer. After treatment participants’ health will be monitored for up to 10 years. See the patient handout for the ALCHEMIST EGFR Trial.

The EGFR Treatment Trial is answering the following research question:

Will adding erlotinib improve overall survival versus a placebo for patients with early-stage EGFR-positive NSCLC who have completed the usual treatment after surgery (chemotherapy, with or without radiation therapy)?

ALCHEMIST - ALK Treatment Trial [E4512]:

Approximately 5% to 6% of people with adenocarcinoma or related types of NSCLC have the ALK genetic rearrangement. Patients whose tumors test positive for this rearrangement, known as an ALK-EML4 fusion, will be referred to the ALCHEMIST ALK treatment trial. In this trial, eligible patients will be randomly assigned to receive the drug crizotinib or a matching placebo pill for 2 years, or until they experience unacceptable toxicity or disease recurrence. After treatment, participants’ health will be monitored for up to 10 years. See the patient handout for the ALCHEMIST ALK Trial.

The ALK Treatment Trial is answering the following research question:

Will adding crizotinib improve overall survival versus a placebo for patients with early-stage ALK-positive NSCLC who have completed the usual treatment after surgery (chemotherapy, with or without radiation therapy)?

ALCHEMIST – Immunotherapy Treatment Trial [ANVIL; EA5142]:

The ALCHEMIST immunotherapy trial was created for patients with early-stage NSCLC whose tumors do not contain the ALK or EGFR gene changes. In addition, patients with early-stage squamous-type NSCLC may also be eligible for the immunotherapy trial. Nivolumab is approved for patients with more advanced stages of NSCLC who have progressed after platinum chemotherapy. This ALCHEMIST treatment trial is testing nivolumab in patients with early-stage lung cancer. In this trial, eligible patients will be randomly assigned to receive the drug nivolumab or be observed. After treatment, participants’ health will be monitored for up to 10 years. See the patient handout for the ALCHEMIST Immunotherapy Trial.

The Immunotherapy Treatment Trial is answering the following research question:

Will additional therapy with immunotherapy (nivolumab) improve overall survival and/or disease-free survival for patients with early-stage NSCLC who have completed the usual treatment after surgery (chemotherapy, with or without radiation therapy)?

The ALCHEMIST studies are being coordinated by the Alliance for Clinical Trials in Oncology and the ECOG-ACRIN Cancer Research Group, members of the NCI-sponsored National Clinical Trials Network (NCTN), as part of the institute’s national strategy for precision medicine.

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