c-Met as a Biomarker in Gastric/GEJ Cancers

Telisotuzumab adizutecan (ABBV-400) is a novel antibody-drug conjugate (ADC) targeting the c-Met protein, which is overexpressed in several cancers, including gastroesophageal junction (GEJ) adenocarcinoma. This ADC is being investigated in a phase 1 clinical trial (NCT05029882) for patients with advanced solid tumors.

Patients with advanced GEJ cancer who had progressed after receiving up to 2 prior lines of chemotherapy were treated with telisotuzumab adizutecan at a dose of 3.0 mg/kg every three weeks. The primary objectives were to assess the safety, tolerability, pharmacokinetics, and efficacy of telisotuzumab adizutecan.

The majority of adverse events (AEs) were gastrointestinal and hematologic in nature. Anemia, nausea, thrombocytopenia, constipation, and neutropenia were the most common AEs. The unadjudicated incidence of interstitial lung disease/pneumonitis was 9.5%. Seven patients discontinued treatment due to AEs.

The overall response rate (ORR) in all enrolled patients was 28.6%. Exploratory biomarker analysis is ongoing to investigate the relationship between c-Met expression and treatment response.

Overall, telisotuzumab adizutecan demonstrated a tolerable safety profile and preliminary antitumor activity in patients with advanced GEJ adenocarcinoma. Further analysis is needed to fully evaluate the efficacy of this ADC in this patient population.

Here, John Strickler, MD, medical oncologist at Duke Cancer Center, discusses targeting c-Met in this disease state.

Transcription:

0:05 | We know that c-Met overexpression is common in many gastroesophageal cancers. And because this appears to be a relevant target, it would be natural to consider an antibody drug conjugate that can use that c-Met expression as an entry point into the cell, thereby delivering that toxic payload. Additionally, this is a disease entity with a still significant unmet need where patients still have fairly short survival times. So it's important for us to bring in new new classes of therapies to try to improve both quality of life and length of life.

0:44 | c-Met expression is interesting. It's seen, depending on which assay you use and cut points, in about 30 to 50% of patients, though that's a pretty wide range. c-Met also can be involved in driving resistance to therapies. So sometimes there will be acquisition of c-Met over over time as a mechanism of resistance. And then also a subset of c–Met-positive cells are also MET-amplified, which would speak to a an addiction to to MET signaling. And those patients are particularly sensitive to an anti–c-Met antibody-drug conjugate.