AVZO-1418/DB-1418 has received fast track designation from the FDA for patients with advanced, EGFR-mutant NSCLC following prior therapy with an EGFR TKI.
The FDA has granted fast track designation to the EGFR/HER3 bispecific antibody-drug conjugate (ADC) AVZO-1418/DB-1418 for the treatment of patients with unresectable, locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring an EGFR exon 19 deletion or exon 21 L858R mutation, whose disease has progressed on or after therapy with an EGFR TKI.1
In January 2025, Avenzo Therapeutics announced that it had entered into an exclusive license agreement with Duality Bio, in which Avenzo will develop, manufacture, and commercialize AVZO-1418/DB-1418 globally, barring China.2
“DualityBio and Avenzo share a common purpose in developing the next generation of oncology therapies that address underserved therapeutic areas,” John Zhu, PhD, founder and chief executive officer of DualityBio, stated at the time of the announcement. “Based on preclinical studies, we believe AVZO-1418/DB-1418 has the potential to offer enhanced therapeutic benefits over other therapies. We look forward to partnering with the Avenzo team to accelerate the development of this program and provide a potential new treatment option to cancer patients.”
AVZO-1418/DB-1418 is topoisomerase-1 inhibitor–based ADC targeting EGFR with medium affinity and HER3 with high affinity.3 In preclinical research presented at the
Moreover, AVZO-1418/DB-1418 displayed higher internalization compared with bivalent ADCs on EGFR/HER3 coexpressing cells, superior in vivo activity in cell line–derived and patient-derived xenograft models of lung cancer, colon cancer, and head and neck cancer relative to BL-B01D1 analogs, and improved efficacy compared with parental bivalent ADCs in NSCLC and renal cell carcinoma models.
In May 2025, Avenzo announced that the FDA had cleared the agent’s investigational new drug (IND) application, allowing the company to launch the first-in-human, open-label phase 1/2 AVZO-1418-1001 trial (NCT07038343).4,5
“The clearance of our IND [application] for AVZO-1418 is a significant achievement for Avenzo as this is our second IND in 3 weeks to receive clearance and our first ADC program to advance into the clinic,” Mohammad Hirmand, MD, cofounder and chief medical officer of Avenzo Therapeutics, stated at the time of the IND approval.4 “We believe AVZO-1418 has a differentiated profile with the potential to benefit patients across various solid tumors. We look forward to initiating our phase 1/2 study later [in 2025] and working closely with our partner, Duality Biotherapeutics.”
The trial is evaluating AVZO-1418/DB-1418 as monotherapy and combination therapy in patients advanced solid tumors.5
To be eligible for enrollment, patients must be between 18 and 75 years of age and have histologically or cytologically confirmed, locally advanced or metastatic epithelial solid tumors with measurable disease by investigator assessment per RECIST 1.1 criteria. Patients must also have an ECOG performance status of 0 or 1, life expectancy of greater than 3 months, and the ability to provide molecular testing results to confirm eligibility and archival tumor samples and/or fresh biopsy as needed.
The primary end points include dose-limiting toxicity (DLT) during the first cycle, maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), and treatment-emergent adverse effects (TEAEs) and lab abnormalities in phase 1. Objective response rate (ORR) will also be evaluated in phase 2. Secondary end points include the evaluation of ORR in phase 1, duration of response, disease control rate, progression-free survival, and overall survival in both phases. Pharmacokinetic parameters will also be evaluated in phase 1. Determination of the RP2D and assessment of TEAEs will also be explored in phase 2.
