A first patient has been dosed in a Phase 1 clinical trial evaluating ADCT-901, targeting kidney-associated antigen 1 (KAAG1), in patients with selected advanced solid tumors with high unmet medical needs. The investigational drug is being developed by ADC Therapeutics.
Research has shown that KAAG1, a novel tumor target for ADC development, is an attractive, novel tumor target for ADCs expressed on the membrane of tumor cells, while its expression on healthy tissue is very limited.[1][2]
KAAG1 is expressed on the surface of cancer cells and rapidly internalizes and co-localizes with lysosomal-associated membrane protein 1 (LAMP-1), a lysosomal marker. This confirms that the target is efficiently transported to the cellular compartment where efficient release of the cytotoxin, the PBD dimer cytotoxin SG3199, is expected. This is followed by apoptosis of the target tumor cell.
“With the FDA’s clearance of the IND application for ADCT-901, we are pleased to quickly move this promising new antibody-drug conjugate into clinical development,” said Joseph Camardo, MD, Chief Medical Officer of ADC Therapeutics.
“There is high expression of KAAG1 in tumors that have few new medicines, such as ovarian and triple-negative breast cancer. We look forward to further evaluating the safety, antitumor activity, and optimal dosing for ADCT-901 in this Phase 1 trial.”
ADCT-901 includes a humanized monoclonal antibody (3A4) directed against human KAAG1 conjugated through a cathepsin-cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD)-dimer cytotoxic alkylating agent.
The cytotoxic included in this investigational ADC is the same as the one included in the same cytotoxin used in loncastuximab tesirine (Zynlonta®; ADC Therapeutics) which is approved by the FDA for the treatment of relapsed or refractory diffuse large b-cell lymphoma after two or more lines of systemic therapy.
The open-label, dose-escalation, and dose-expansion clinical trial will evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of ADCT-901 as monotherapy in patients with selected advanced solid tumors. For more information about the Phase 1 trial.
Clinical trial
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-901 in Participants With Selected Advanced Solid Tumors – NCT04972981
Highlights of Prescribing Information
Loncastuximab tesirine (Zynlonta®; ADC Therapeutics)[Prescribing Information]
References
[1] Van Den Eynde BJ, Gaugler B, Probst-Kepper M, Michaux L, Devuyst O, Lorge F, Weynants P, Boon T. A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription. J Exp Med. 1999 Dec 20;190(12):1793-800. doi: 10.1084/jem.190.12.1793. PMID: 10601354; PMCID: PMC2195717.
[2] Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, et al. The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. doi: 10.1038/nature02055. PMID: 14574404.
