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

Conditions

• Lung Cancer
• Non Small Cell Lung Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Amivantamab 1050mg — DRUG
  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.
• Amivantamab 1400mg — DRUG
  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.
• Amivantamab (to be determined) — DRUG
  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
• Amivantamab (to be determined) — DRUG
  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

Study Details

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.

Key Dates

Start date

Jul 17, 2023

Status verified

Jan 2026

Primary completion

Jan 31, 2027

Completion

Jan 31, 2028

Study Design

Enrollment

12 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Dose Finding (Safety Lead-In) Cohort (<80 kg)
  To estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in adult participants with advanced NSCLC with ALK, ROS1, and RET gene fusions.
• Experimental: Dose Finding (Safety Lead-In) Cohort (≥80 kg)
  To estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in adult participants with advanced NSCLC with ALK, ROS1, and RET gene fusions.
• Experimental: Dose Expansion Cohort (<80 kg)
  To estimate the objective response rate (ORR) of amivantamab in combination with common TKIs used in ALK, ROS1, and RET advanced NSCLC progressing on TKIs.
• Experimental: Dose Expansion Cohort (≥80 kg)
  To estimate the objective response rate (ORR) of amivantamab in combination with common TKIs used in ALK, ROS1, and RET advanced NSCLC progressing on TKIs.

Primary Outcome Measure

Determine the MTD in adult participants with advanced NSCLC [ Time Frame: 18 months ]

Locations (4)

Find similar trials in Duarte, CA

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