Amivantamab With Tyrosine Kinase Inhibitors (TKI) for Advanced NSCLC With ALK, ROS1, or RET Alter… (NCT05845671) | Clinical Trial Compass
Active — Not RecruitingPhase 1/2
Amivantamab With Tyrosine Kinase Inhibitors (TKI) for Advanced NSCLC With ALK, ROS1, or RET Alterations
United States12 participantsStarted 2023-07-17
Plain-language summary
Although non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK), c-ros oncogene 1(ROS1), and ret proto-oncogene (RET) gene fusions initially respond well to tyrosine kinase inhibitor (TKI) therapies, acquired resistance is inevitable. In many of these cases, increased activation of the erythroblastic leukemia viral oncogene homologue (ERBB) or cMet pathways appears to be a bypass signaling mechanism that allows these cancer cells to circumvent the selective pressure from TKIs. Recent data have suggested that these pathways compensate for each other in situations where one pathway is inhibited, leading to "kinase switch" drug resistance. Thus, the expected inhibition of both pathways via treatment with the amivantamab and combination TKI combination may improve overall efficacy by limiting the compensatory pathway activation.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Provision to sign and date the informed consent form.
. Stated willingness to comply with all study procedures and be available for the duration of the study.
. Participant is ≥ 18 years of age.
. Participant has histologic or cytologic confirmation of locally advanced (unresectable) or metastatic NSCLC with a known (and documented) ALK, ROS1, or RET fusion based on approved diagnostic testing methods specified below. Not that NGS testing is required for all participants, but screening if any of the test below are positive.
. Participants must have clinical progression on at least one prior FDA-approved TKI. They must be on a TKI at the same dose for at least 8 weeks without radiographic progression or clinical intolerance of the TKI prior to enrolling on this study. TKIs that will be considered include (but not limited to):
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Determine the MTD in adult participants with advanced NSCLC
Timeframe: 18 months
2
Determine the recommended phase 2 dose in adult participants with advanced NSCLC
Timeframe: 20 months
3
Estimate the objective response rate (ORR) of amivantamab in combination with common TKIs used in ALK, ROS1, and RET advanced NSCLC progressing on TKIs
. Participant has received an investigational drug within a 28-day period (or within 5 half-lives, whichever is shorter) before the first dose of study drug or is currently participating in another interventional clinical trial, unless in the opinion of the Sponsor-Investigator, the medication will not interfere with the study procedures or compromise subject safety.
. The participant cannot have ever received an EGFR TKI (e.g. osimertinib), EGFR- directed monoclonal antibody (e.g. cetuximab), MET TKI (e.g. capmatinib, tepotinib), MET-directed monoclonal antibody (e.g. amivantamab) or MET-directed antibody-drug conjugate (e.g. telisotuzumab vedotin) prior to study entry. For patients with ALK or ROS1 NSCLC, crizotinib cannot be used within 3 months of screening.
. Participants who have progressed on a TKI in less than 8 weeks
. The participant has evidence of neuroendocrine differentiation or small cell transformation on the screening biopsy.
. The patient has no evidence of an ALK, ROS1, and RET gene fusion as determined by molecular testing. Acquired resistance mechanisms detected through NGS (or FISH) testing for which alternative therapies exist may potentially be eligible after consultation with the PI.
. Participants with active, symptomatic, central nervous system disease defined as follows:
. Leptomeningeal disease.
. Symptomatic cord compression from metastatic disease.