The U.S. Food & Drug Administration (FDA) has provided clearance of the Investigational New Drug (IND) application for a Phase 1 Tiffany-01 study (NCT06597721) evaluating ADCE-T02 (previously known as AMT 754; see Drugmap), a novel antibody-drug conjugate (ADC) being developed by Adcendo.*
Tiffany-01 is an ongoing first-in-human (FIH) Phase I multicenter, open-label, dose escalation study of ADCE-T02 as a monotherapy in patients with advanced or metastatic solid tumors. The primary objectives of the study are to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) and schedule of ADCE-T02 monotherapy in addition to assessing ADCE-T02 safety and tolerability.
The secondary objectives are to characterize the pharmacokinetics and to evaluate the preliminary efficacy of ADCE-T02. The study is currently recruiting in Australia and will start recruiting in the U.S. in the next few months.
ADCE-T02 is a highly differentiated anti-TF ADC, and the first ADC with a Topoisomerase I (TOP1) inhibitor-based linker/payload,** clinically developed in Australia and the U.S. Its unique antibody design minimizes the impact on the coagulation pathway, while the T1000-exatecan linker-payload technology platform, which has played a significant role in multiple successful ADC pipelines, has been shown to amplify the bystander effect, improve linker stability, and has the potential to overcome emerging resistance mechanisms.
The differentiated features are expected to translate into a superior therapeutic window, a better safety profile, enhanced response rates and longer duration of therapy.
Validated target
Tissue Factor (TF), also called Platelet Tissue Factor or Coagulation factor III, is an initiator of the blood coagulation pathway which has been investigated regarding its relationship with cancer, has a strong over-expression in multiple tumor indications with high unmet medical need including Cervical Cancer, Head and Neck Cancer, Colorectal Cancer, Non-Small Cell Lung Cancer, and Pancreatic Ductal Adenocarcinoma. TF expression in cancer is associated with poor prognosis.[1][2]
“Tissue factor (TF) is a validated ADC target with over-expression in many high unmet need solid tumor indications, however, the currently approved TF targeting ADC has severe limitations due to a suboptimal side effect profile and a limited therapeutic window,” explained Lone Harild Ottesen, MD, Ph.D., Chief Medical Officer of Adcendo.
“The highly differentiated profile of ADCE-T02, based on the use of an improved monoclonal antibody and a next generation Topoisomerase I inhibitor linker/payload technology, could overcome those limitations and offer an enhanced therapeutic window and improved side effect profile, which may lead to better clinical outcomes for patients,” Ottesen further noted.
“The U.S. IND clearance of ADCE-T02 is an important milestone for our program and our company, and we look forward to initiating patient enrollment in the U.S. and working closely with all of our investigators to evaluate the therapeutic utility of this drug in multiple advanced solid tumor indications,” Ottesen added.
“ADCs have in the past years shown highly encouraging results and have already become Standard of Care (SoC) in quite a number of solid tumor indications. ADCE-T02 represents an attractive new option to explore in advanced solid tumors with high unmet need,” said Prof. Vinod Ganju MBBS FRACP, Director of Peninsula and Southeast Oncology (PASO), Melbourne, Australia and Principal Investigator of Tiffany-01.
“I am pleased to be working with Adcendo to develop ADCE-T02, potentially offering a broader therapeutic window and a better safety profile for our patients,” Ganju concluded
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Note: * In late August 2024 Adcendo and Multitude Therapeutics signed a licensing agreement for the development of a ADCE-T02. Under this agreement, Adcendo will obtain the exclusive development and commercialization rights, except for the Greater China region (Mainland China, Hong Kong Special Administrative Region, Macao Special Administrative Region, and Taiwan) where Multitude Therapeutics retains development and commercialization rights. Although the companies did not provide a financial breakdown of the agreement, it is understood that Multitude Therapeutics received upfront and is entitled to potential milestone payments that could be more than of US $ 1 billion as well as single-digit to low double-digit tiered royalties.
* Tisotumab vedotin (Tivdak®; Genmab/Pfizer/Seagen) was the first FDA approved ADC targeting tissue factor (TF) for the treatment of adult patients with recurrent or metastatic cervical cancer whose disease has progressed during or after chemotherapy. Other Investigational ADCs targeting TF include monomethyl auristatin E (MMAE) or deruxtecan (DXd) as a payload.
Clinical trials
ADCE-T02, a Tissue Factor Targeted Antibody-Drug Conjugate, in Patients With Selected Advanced Solid Tumours – ClinicalTrials.gov ID NCT06597721
Reference
[1] Hisada Y, Mackman N. Tissue Factor and Cancer: Regulation, Tumor Growth, and Metastasis. Semin Thromb Hemost. 2019 Jun;45(4):385-395. doi: 10.1055/s-0039-1687894. Epub 2019 May 16. PMID: 31096306; PMCID: PMC6546519.
[2] Breij EC, de Goeij BE, Verploegen S, Schuurhuis DH, Amirkhosravi A, Francis J, Miller VB, Houtkamp M, Bleeker WK, Satijn D, Parren PW. An antibody-drug conjugate that targets tissue factor exhibits potent therapeutic activity against a broad range of solid tumors. Cancer Res. 2014 Feb 15;74(4):1214-26. doi: 10.1158/0008-5472.CAN-13-2440. Epub 2013 Dec 26. PMID: 24371232.
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