Study ID: NRG-LU003
Targeted treatment for ALK-positive patients who have previously been treated for non-squamous non-small cell lung cancer
This phase II study seeks to determine how well a combination of medications work in patients with previously treated stage 4 non-squamous non-small cell lung cancer (NSCLC) that is caused by a genetic mutation of the ALK gene. Eligible participants are those who have already been treated with a second-generation ALK inhibitor, but their disease has progressed.
Patients’ tumors are biopsied to determine the genetic mutation found in their tumor cells. If certain mutations are discovered, the patient may be eligible to participate in one of the arms of this trial.
Overall, the study is testing several FDA-approved cancer treatment options and one experimental medication.
This phase II study seeks to determine how well a combination of different biomarker/ALK inhibitors work in treating patients with stage IV ALK-positive NSCLC.
The study is comparing several ALK inhibitors, including lorlatinib, ceritinib, alectinib, brigatinib, ensartinib and crizotinib. It also is comparing pemetrexed plus cisplatin and/or carboplatin to determine if chemotherapy may work equal, better or worse in these patients. Tumors are biopsied for genetic mutations, and participants are placed into appropriate study arms as follows:
- ALK L1198F mutation (alone or in combination with another ALK mutation) receive crizotinib
- Cy1156Y mutation receives either lorlatinib, alectinib or brigatinib
- Compound mutations receive lorlatinib
- F1174 receives either lorlatinib, alectinib or brigatinib
- G1202 (including G1202del and G1202R) receives either lorlatinib or brigatinib
- I1171 mutation receives either lorlatinib, ceritinib or brigatinib
- L1196 (including L1196M) mutation receives either lorlatinib, ceritinib, alectinib, brigatinib or ensartinib
- MET amplification receives crizotinib
- no ALK-resistant mutations receive either lorlatinib, ceritinib, alectinib, brigatinib, ensartinib, or pemetrexed IV with either cisplatin or carboplatin
- V1180 mutation receives either lorlatinib, ceritinib or brigatinib
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
- Must have been diagnosed with stage 4 ALK-positive NSCLC
- Must have disease progression after treatment with one second-generation ALK inhibitor
Other inclusion and exclusion criteria apply