Telisotuzumab adizutecan

Table of contents

• What is telisotuzumab adizutecan?
• How does telisotuzumab adizutecan work?
• Which conditions is telisotuzumab adizutecan studied for?
• How is telisotuzumab adizutecan given?
• What do the clinical trials show?
• Who can take part in these trials?
• What are the trials measuring?

What is telisotuzumab adizutecan?

Telisotuzumab adizutecan is an investigational antibody-drug conjugate. It is a protein-based substance, not a chemically synthesised small molecule. The registry records list it as the test substance in five trials and describe it as having no marketing authorisation, meaning it is still being studied and is not yet approved as a medicine.^[1] The product is supplied by AbbVie Deutschland GmbH & Co. KG.^[1] The substance also appears under the development code ABBV-400 in several registry records.^[8]

How does telisotuzumab adizutecan work?

Telisotuzumab adizutecan is an antibody-drug conjugate. The antibody portion targets the c-Met protein, which is found at higher levels on the surface of some cancer cells. One Phase 3 trial specifically enrols participants with metastatic colorectal cancer whose tumours express c-Met protein above a defined cutoff.^[9] Another Phase 2 study enrols people with solid tumours that harbour MET amplification, a genetic change that increases c-Met signalling.^[11] The conjugate design means the drug is intended to deliver a toxic payload preferentially to cells that carry the target protein.

Which conditions is telisotuzumab adizutecan studied for?

• Metastatic colorectal cancer — studied in several trials, including Phase 2 and Phase 3 studies, alone or with bevacizumab, fluorouracil, folinic acid, and other drugs.^[1][6]
• Colorectal cancer without radiographic evidence of disease — a Phase 2 study tests the drug as monotherapy in people with circulating tumour DNA-positive disease after adjuvant treatment.^[4]
• Non-squamous non-small cell lung cancer — studied in Phase 1, Phase 4 and other trials, including EGFR-mutated disease, alone or with osimertinib or checkpoint inhibitors.^[3][5]
• Gastric, gastroesophageal junction and oesophageal adenocarcinoma — a Phase 2 study tests the drug with fluorouracil, folinic acid and budigalimab as first-line treatment.^[2]
• Metastatic pancreatic ductal adenocarcinoma — a Phase 4 trial combines the drug with FOLFOX in the first-line setting and plans to enrol 900 participants.^[7]
• Locally advanced or metastatic solid tumours with MET amplification — a Phase 2 study enrols participants aged 12 years or older across tumour types.^[11]

How is telisotuzumab adizutecan given?

Telisotuzumab adizutecan is given by intravenous infusion or intravenous injection. The registered pharmaceutical form is a solution for infusion.^[1] Across the trials, the drug is administered intravenously, either alone or in combination with other cancer medicines such as bevacizumab, osimertinib, fluorouracil, folinic acid, oxaliplatin, carboplatin, cisplatin, pemetrexed, budigalimab, pembrolizumab, panitumumab, amivantamab, trifluridine and tipiracil.^[1][2][5]

What do the clinical trials show?

The EU Clinical Trials Information System and ClinicalTrials.gov together list 11 registered trials for telisotuzumab adizutecan. The studies span Phase 1 through Phase 4. One Phase 1 study in advanced or metastatic non-squamous non-small cell lung cancer enrols 252 participants and combines the drug with the PD-1 immune checkpoint inhibitors budigalimab or pembrolizumab.^[3] Phase 2 studies cover metastatic colorectal cancer, colorectal cancer without radiographic disease, gastric and gastroesophageal junction adenocarcinoma, and MET-amplified solid tumours.^[1][2][11]Phase 3 trials compare the drug against standard treatments in refractory metastatic colorectal cancer, with the largest of these planning 698 participants.^[9][6] Two Phase 4 studies are registered, one in EGFR-mutated non-squamous non-small cell lung cancer with 224 participants and one in metastatic pancreatic ductal adenocarcinoma with 900 participants.^[10][7] One Phase 3 trial in refractory metastatic colorectal cancer is already completed.^[9]

Who can take part in these trials?

Eligibility varies by study. Most trials enrol adults with advanced or metastatic disease. One Phase 2 study in MET-amplified solid tumours accepts participants aged 12 years or older.^[11] Some trials select participants by molecular features: one Phase 3 colorectal cancer study requires c-Met protein expression above a defined cutoff,^[9] and two lung cancer studies enrol people with EGFR-mutated non-squamous non-small cell lung cancer.^[5][10] One colorectal cancer study enrols people with circulating tumour DNA-positive disease and no radiographic evidence of cancer after adjuvant treatment.^[4]

What are the trials measuring?

The most common endpoint is objective response, meaning a confirmed complete or partial shrinkage of the tumour as assessed by investigators or by blinded independent central review using RECIST version 1.1 criteria.^[1][9] Progression-free survival, the time from first dose until the cancer grows or death from any cause, is a primary endpoint in several Phase 2, Phase 3 and Phase 4 studies.^[2][5] Overall survival is a primary or key secondary endpoint in the Phase 3 and Phase 4 colorectal and pancreatic cancer studies.^[9][6][7] Two trials also measure disease-free survival or dose-limiting toxicity.^[3][4]