Part 1 Medical Trial NCT06225427 sponsored by The College of Colorado, Denver with Janssen Analysis and Growth, LLC
Amivantamab With Tyrosine Kinase Inhibitors (TKIs) for Superior NSCLC With ALK, ROS1, or RET Alterations
https://clinicaltrials.gov/research/NCT05845671
Principal Investigator: Dr. Tejas Patil
College of Colorado Examine Contact: Febin Elias; 303-724-9459; febin.elias@cuanschutz.edu
College of Michigan Examine Contact: Dhaman Bansal; shbansl@med.umich.edu
Who is that this trial for: This trial is for sufferers with one among three types of non-small cell lung most cancers (NSCLC) – ALK, ROS1, or RET – who’re progressing on their present TKI below sure situations, and are prepared to strive an experimental drug mixture as a way to lengthen the lifetime of their present TKI. Amivantamab is a bi-specific antibody concentrating on the cell survival pathways MET and EGFR. The trial could also be most applicable for sufferers who’re progressing and not using a targetable mutation or clearly recognized driver of their most cancers progress.
Inclusion standards: The trial will research the security, unwanted side effects, finest dose, and efficacy of amivantamab when paired with TKIs for particular oncogene-driven NSCLC, together with ALK. The goal inhabitants for this research will probably be grownup sufferers with at present progressing NSCLC harboring an ALK, ROS1, or RET fusion on an FDA-approved TKI. Sufferers will need to have been on their present TKI on the similar dose for not less than 8 weeks with out radiographic development or scientific intolerance to the TKI previous to enrolling on this research. In different phrases, previous to development, the affected person will need to have been secure on the TKI for not less than 8 weeks. Members will need to have not less than 1 measurable lesion utilizing computed tomography (CT) scan or magnetic resonance imaging (MRI). For ALK sufferers, TKIs included are alectinib, brigatinib, lorlatinib, and others. Sufferers are anticipated to remain on their present TKI with no washout, and obtain further periodic infusions of amivantamab on the trial clinics. Acceptable ages are 18-90 years.
Exclusion standards: The affected person can’t have ever obtained a previous EGFR or MET TKI or every other EGFR or MET-directed therapy as a way to take part, nonetheless prior crizotinib therapy is allowed if discontinued three months previous to trial screening. Different prior remedies together with chemotherapy, immune checkpoint inhibitors, surgical procedure, and radiotherapy will need to have been accomplished by various time durations as much as one month. Trial exclusion standards embrace a number of pre-existing medical situations: see https://clinicaltrials.gov/research/NCT05845671.
Some Particulars: Estimated enrollment within the lead-in cohort is 10-12 sufferers, with a complete of 16-35 whole sufferers anticipated to be accrued. Examine length is estimated to be a complete of 4 years, with 3 years of participant enrollment and 1 yr for evaluation. A recent pre-treatment biopsy or equal archival materials from a tumor biopsy collected prior to review therapy is required. Blood samples will probably be routinely collected for lab testing, and CT scans with distinction will probably be carried out periodically. Infusion frequency at this writing is each three weeks, however could also be modified to each two weeks.
Scientific rationale: Amivantamab (aka Rybrevant) is a bispecific antibody that targets the EGFR and MET pathways. It was accredited by the FDA in 2021 for sufferers with NSCLC harboring EGFR exon 20 insertion mutations, together with carboplatin and pemetrexed. The trial speculation is that EGFR and MET pathways are utilized by most cancers cells to avoid the selective stress from TKIs as a method of survival. Persevering with the ALK, ROS1, or RET TKI after development and including amivantamab represents a rational mixture technique, even when the affected person checks destructive for EGFR or MET amplification. It’s thought that there should be EGFR-MET signaling that normal biomarker testing isn’t discovering, even within the absence of EGFR-MET amplification. Latest information means that these pathways compensate for one another in conditions the place one pathway is inhibited, resulting in “kinase swap” drug resistance. Thus, the anticipated inhibition of a number of pathways by way of mixture therapy with amivantamab and a TKI might enhance general efficacy by limiting the compensatory pathway activation. In vitro and in vivo research confirmed that amivantamab was capable of disrupt EGFR and MET signaling capabilities by blocking ligand binding and, in exon 20 insertion mutation fashions, degradation of EGFR and MET. The presence of EGFR and MET on the floor of tumor cells additionally permits for concentrating on of those cells for destruction by immune effector cells, corresponding to pure killer cells and macrophages, by antibody-dependent mobile cytotoxicity (ADCC), and by cells ingesting one another (trogocytosis).
Availability: The trial is open at two places of the College of Colorado in Denver, the place the principal investigator is Dr. Tejas Patil, and a sub-investigator is Dr. Ross Camidge. Additionally it is open at College of Michigan, the place the principal investigator is Dr. Angel Qin. Janssen Analysis and Growth is an entirely owned subsidiary of Johnson and Johnson, an American pharmaceutical firm ranked #2 on the earth with revenues of $54.76B in 2023.
Jeffrey M. Sturm BS, MA, MBA
ALK Constructive, Inc. www.alkpositive.org
Member Medical Trials Committee
Member Board of Administrators
ALK Constructive NSCLC Survivor