NCT05845671

Amivantamab With Tyrosine Kinase Inhibitors (TKI) for Advanced NSCLC With ALK, ROS1, or RET Alterations

A Phase 1 / 2, Open Label, Study of Amivantamab (JNJ-61186372) Among Participants With Advanced NSCLC Harboring ALK, ROS1, and RET Gene Fusions in Combination With Tyrosine Kinase Inhibitors

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Lung Cancer
• Non Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Amivantamab 1050mg	Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies amivantamab was able to disrupt EGFR and MET signaling functions through blocking ligand binding and, in exon 20 insertion mutation models, degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells also allows for targeting of these cells for destruction by immune effector cells, such as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity (ADCC) and trogocytosis mechanisms, respectively.
DRUG	Amivantamab 1400mg	Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies amivantamab was able to disrupt EGFR and MET signaling functions through blocking ligand binding and, in exon 20 insertion mutation models, degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells also allows for targeting of these cells for destruction by immune effector cells, such as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity (ADCC) and trogocytosis mechanisms, respectively.
DRUG	Amivantamab (to be determined)	Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies amivantamab was able to disrupt EGFR and MET signaling functions through blocking ligand binding and, in exon 20 insertion mutation models, degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells also allows for targeting of these cells for destruction by immune effector cells, such as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity (ADCC) and trogocytosis mechanisms, respectively. Dose will be determine after the Safety Lead-In
DRUG	Amivantamab (to be determined)	Amivantamab is a bispecific antibody that binds to the extracellular domains of EGFR and MET. In in vitro and in vivo studies amivantamab was able to disrupt EGFR and MET signaling functions through blocking ligand binding and, in exon 20 insertion mutation models, degradation of EGFR and MET. The presence of EGFR and MET on the surface of tumor cells also allows for targeting of these cells for destruction by immune effector cells, such as natural killer cells and macrophages, through antibody-dependent cellular cytotoxicity (ADCC) and trogocytosis mechanisms, respectively. Dose will be determine after the Safety Lead-In

Timeline

• Start date: 2023-07-17
• Primary completion: 2027-01-01
• Completion: 2028-01-01
• First posted: 2023-05-06
• Last updated: 2026-01-14

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study