Izalontamab brengitecan

Izalontamab brengitecan, also known as BL-B01D1 or iza-bren, is an investigational antibody-drug conjugate being studied in several advanced cancers. It is a protein-based substance supplied as a powder for solution for infusion and given by intravenous use.^[4] The substance appears as the test medicine in three of the four registered trials.^[4][1][2]

Table of contents

• What is izalontamab brengitecan?
• How does izalontamab brengitecan work?
• Which conditions is it studied for?
• How is izalontamab brengitecan given?
• What do the clinical trials show?
• Who can take part in these trials?
• What are the trials measuring?
• What side effects are known?

What is izalontamab brengitecan?

Izalontamab brengitecan is a first-in-class bispecific antibody-drug conjugate targeting EGFR and human epidermal growth factor receptor 3 (HER3).^[5] It is an investigational substance with no marketing authorisation in the product records.^[4] The substance is a protein-based medicine, specifically a protein of the "Protein - Other" category, and is supplied by Systimmune Inc.^[4] In the registry it also appears under the product name BL-B01D1.^[4]

How does izalontamab brengitecan work?

Izalontamab brengitecan is an antibody-drug conjugate, a type of medicine that links an antibody to a cancer-killing drug. The antibody part is designed to recognise and attach to two targets on cancer cells: EGFR and HER3.^[5] This dual targeting is intended to deliver the attached drug directly to cancer cells, which may help to spare healthy cells. The exact mechanism by which blocking or activating these receptors affects tumour growth is described in the source as targeting EGFR and HER3 with preclinical and early clinical activity.^[5]

Which conditions is it studied for?

The authorised trials cover four disease areas:

• Triple-negative breast cancer — a form of breast cancer that lacks three common receptors and is being studied in a Phase 4 trial.^[4]
• EGFR-mutated non-small cell lung cancer — a type of lung cancer with a specific genetic change, studied in a Phase 4 trial.^[2]
• Metastatic urothelial cancer — cancer of the urinary tract that has spread, studied in a Phase 4 trial.^[3]
• Advanced solid tumours — a broad category of cancers, studied in a Phase 1 trial that includes lung cancer groups.^[1]

A published pooled analysis also reports activity in EGFR-mutated non-small cell lung cancer after progression on EGFR tyrosine kinase inhibitors.^[5]

How is izalontamab brengitecan given?

Izalontamab brengitecan is supplied as a powder for solution for infusion and is given by intravenous use, meaning it is administered directly into a vein.^[4] The published pooled analysis describes a recommended Phase 2 dose of 2.5 mg/kg given on days 1 and 8 of a 3-week cycle.^[5] The registry records do not report a dose for the substance in the authorised trials, where the dose is listed as 9999 mg or 9999 mg/kg, indicating that the dose was not reported in the register.^[4][2][3]

What do the clinical trials show?

Four trials are currently authorised. One is a Phase 1 trial in advanced solid tumours with 276 participants, and three are Phase 4 trials: one in triple-negative breast cancer with 500 participants, one in EGFR-mutated non-small cell lung cancer with 510 participants, and one in metastatic urothelial cancer with 461 participants.^[1]–[4]

A published pooled analysis of earlier Phase I and Phase II trials in EGFR-mutated NSCLC reported a confirmed objective response rate of 47.4% and a disease control rate of 81.3% in 171 patients.^[5] In that analysis, median progression-free survival was 6.9 months and median overall survival was 24.8 months.^[5]

Who can take part in these trials?

The Phase 1 trial enrols adult participants with advanced solid tumours, including two groups of lung cancer patients: those with EGFR-mutated non-small cell lung cancer and those with EGFR wild-type non-small cell lung cancer.^[1] The Phase 4 breast cancer trial enrols patients with previously untreated, locally advanced, recurrent inoperable, or metastatic triple-negative breast cancer who are ineligible for anti-PD(L)1-based treatments.^[4] The Phase 4 lung cancer trial enrols patients with EGFR-mutated non-small cell lung cancer whose disease has progressed after third-generation EGFR tyrosine kinase inhibitor therapy.^[2] The Phase 4 urothelial cancer trial enrols patients with metastatic urothelial cancer whose disease has progressed on or after immunotherapy.^[3]

What are the trials measuring?

The Phase 1 trial measures safety, including the number of participants with adverse events, serious adverse events, dose-limiting toxicities, and adverse events leading to discontinuation or death.^[1] The Phase 4 breast cancer trial measures progression-free survival by blinded independent central review, which shows how long it takes for the disease to get worse on imaging such as CT scans.^[4] The Phase 4 lung cancer trial also measures progression-free survival by RECIST v1.1 per blinded independent central review.^[2] The Phase 4 urothelial cancer trial measures progression-free survival and overall survival in Phase 3, and reviews efficacy, safety, tolerability, and pharmacokinetic data in Phase 2.^[3]

What side effects are known?

The published pooled analysis reports safety data but the abstract provided does not list specific side effects by name.^[5] The Phase 1 trial is designed to measure adverse events, serious adverse events, and dose-limiting toxicities, but the registry records do not report the specific side effects observed.^[1]