AVZO-1418/DB-1418 Earns FDA Fast Track Designation For EGFR-Mutated NSCLC

The FDA has granted fast track designation to AVZO-1418/DB-1418, an investigational EGFR/HER3 bispecific antibody drug conjugate (ADC), for the treatment of patients with EGFR-mutated, unresectable, locally advanced, or metastatic non–small cell lung cancer (NSCLC) who experienced disease progression on or after receipt of an EGFR tyrosine kinase inhibitor (TKI), according to a news release from the developer, Duality Biotherapeutics.¹

Additionally, the developers entered an exclusive license agreement with Avenzo Therapeutics in January 2025.² Within this partnership, Avenzo is tasked with developing, manufacturing, and commercializing the investigational therapy as a potential best-in-class EGFR/HER3 bispecific ADC.

The investigational ADC is being evaluated in an open-label phase 1/2 study (NCT07038343) to assess its safety, tolerability, and preliminary activity in advanced solid tumors. The phase 1 dose-escalation portion of the trial was established to determine the maximum tolerated dose (MTD) and preliminary recommended phase 2 dose (RP2D) of the agent as a monotherapy.³ The antitumor activity of AVZO-1418 alone and potentially as part of a combination regimen was assessed in the phase 2 dose-expansion portion of the trial.

In May 2025, the FDA cleared the investigational new drug (IND) application for AVZO-1418, according to a news release from Avenzo.⁴ Under the IND, the developers initiated the phase 1/2 trial.

“The clearance of our [investigational NDA] 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, co-founder and chief medical officer of Avenzo Therapeutics, expressed in the news release on the IND.³ “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 this year and working closely with our partner, Duality Biotherapeutics.”

According to preclinical data presented at the American Association for Cancer Research Annual Meeting (AACR), the agent exhibited additive binding in EGFR and HER3 co-expressing tumor cells, in addition to demonstrating efficacy in in vivo xenograft models in an EGFR TKI-resistant NSCLC model, among other tumor models.

Patients in the phase 1/2 trial 18 to 75 years old received intravenous AVZO-1418 as a treatment for locally advanced or metastatic epithelial solid tumors.

The primary end points of the phase 1 trial included dose-limiting toxicities in the first cycle of study treatment, MTD or R2PD, and treatment-emergent adverse effects. In the phase 2 portion of the trial, the primary end point was objective response rate. Secondary end points included duration of response, disease control rate, progression-free survival, overall survival, and pharmacokinetics.

Those eligible for trial enrollment had an ECOG performance status of 0 or 1, a life expectancy of more than 3 months, histological or cytological confirmation of locally advanced or metastatic epithelial solid tumors, and measurable disease per RECIST v1.1 criteria. Additionally, patients must have consented to provide molecular test results, archival tumor samples, and/or fresh biopsies when applicable.

Those ineligible for trial enrollment included those with uncontrolled hypertension, those with active central nervous system metastases, and those with a history of drug-induced interstitial lung disease (ILD). Additionally, those with a history of serious cardiovascular conditions; infections requiring intravenous antibiotics, antivirals, or antifungals within 2 weeks prior to first study dose; and those with a history of solid organ transplant were excluded from trial enrollment.

References

1. Fast track designation granted for AVZO-1418/DB-1418, a potential best-in-class EGFR/HER3 bispecific antibody-drug conjugate, for the treatment of patients with EGFR-mutated TKI-pretreated NSCLC. News release. DualityBio. November 10, 2025. Accessed November 13, 2025. https://tinyurl.com/2erppzpr
2. Avenzo Therapeutics and DualityBio announce exclusive global license for potential best-in-class EGFR/HER3 antibody-drug conjugate. News release. Avenzo Therapeutics. January 7, 2025. Accessed November 13, 2025. https://tinyurl.com/y3v388rt
3. Study of AVZO-1418 as a single agent and in combination therapy in patients with locally advanced or metastatic solid tumors (AVZO-1418-1001). Clinicaltrials.gov. Updated September 19, 2025. Accessed November 13, 2025. https://tinyurl.com/4zkcv5m7
4. Avenzo Therapeutics announces FDA clearance of investigational new drug application for AVZO-1418, a potential best-in-class, novel EGFR/HER3 bispecific