The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ADRX-0706, for the treatment of patients with locally advanced or metastatic squamous cell cervical cancer.
ADRX-0706 is a Nectin-4 ADC is a fully proprietary antibody-drug conjugates (ADC) being developed by Adcentrx (see ADC Drugmap) and evaluated in the Phase 1b portion of an ongoing Phase 1a/b clinical trial (NCT06036121) for the treatment of select advanced solid tumors, including cervical cancer.
This first-in-human Phase 1a/b study is an open-label, two-part trial being conducted at sites in the U.S. and China.
The completed Phase 1a portion consisted of a dose escalation of ADRX-0706 to evaluate initial safety and tolerability in patients with select advanced solid tumors, and to identify the recommended dose to be used in Phase 1b. This ongoing second portion of the study aims to further evaluate ADRX-0706’s safety and tolerability, preliminary efficacy, and optimal dose in urothelial, triple-negative breast and cervical cancers.
Cervical cancer
Cervical cancer represents a significant unmet need, particularly for patients whose disease progresses following initial treatment. Nectin-4 is highly expressed in cervical cancer, making it a compelling tumor type for treatment with a Nectin-4 ADC.
A novel ADC
The antibody component is a novel fully human IgG1 targeting Nectin-4, a cell surface adhesion protein with high expression in multiple solid tumors and limited expression in normal tissues. Nectin-4 is associated with poor disease prognosis and is a validated target for ADCs. [1]
The investigational agent includes a Nectin-4 targeting antibody linked to a proprietary tubulin inhibitor payload, AP052, through Adcentrx’s innovative i-Conjugation® technology platform – a core component in the design of the company’s ADCs. The platform utilizes a cleavable linker and stable conjugation chemistry to enhance payload delivery. This novel technology enables a highly stable ADC with a drug-antibody ratio of eight (DAR 8) with a substantially expanded therapeutic window as demonstrated in preclinical studies.
ADRX-0706 has a favorable pharmacokinetic and safety profile in preclinical models and has demonstrated significant efficacy across a variety of tumor indications in vitro and in vivo.
ASCO 2025
Interim data from the completed Phase 1a dose escalation portion of the study will be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO), held May 30 – June 3, 2025) in Chicago, Illinois. Early findings demonstrated a differentiated safety and pharmacokinetic profile, including a notably lower incidence of adverse events such as peripheral neuropathy, along with preliminary efficacy signals across multiple tumor types.
Poster presentation
- Title: Preliminary results from a first-in-human phase 1 dose escalation trial of ADRX-0706, a next generation Nectin-4 ADC, in subjects with advanced solid tumors
- Abstract Number: 3018
- Session Date & Time: Monday, June 2, 1:30 p.m. – 4:30 p.m. CST
- Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Fast Track
“The Fast Track designation granted by the FDA underscores the significant unmet need in advanced cervical cancer and marks another meaningful milestone for Adcentrx,” said Hui Li, Ph.D., Founder and Chief Executive Officer of Adcentrx.
“This recognition, together with the early clinical signals observed for ADRX-0706, reinforces the best-in-class potential of our Nectin-4 ADC and provides the opportunity for enhanced regulatory dialogue as we continue advancing this important program through clinical development,” Li concluded.
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Clinical Trials
A Study of ADRX-0706 in Select Advanced Solid Tumors – ClinicalTrials.gov ID NCT06036121
Reference
[1] Maria Shahmoradgoli, Andrew Hau, Dong Jun Lee, Anna Wang, Peter P. Challita, Oscar Betancourt, Wes Sisson, Mario M. Kuo, Kris Zhang, Albert Goldson, Sam Janssen, Paul Datta, Felipe Acosta, Alexander Chu-Kung, Hui Li, Pia M. Challita-Eid, Sabine Rottmann. ADRX-0706 Nectin-4 antibody-drug conjugate PK/PD characterization elucidates its widened therapeutic window [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1902.
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