FDA Fast-Tracks Bispecific ADC AVZO-1418 for EGFR-Mutated Pretreated NSCLC

The FDA has granted fast track designation to the EGFR/HER3 bispecific antibody-drug conjugate (ADC) AVZO-1418 for treatment of patients with EGFR-mutated, tyrosine kinase inhibitor (TKI)–pretreated non–small cell lung cancer (NSCLC).¹

The FDA’s fast track program is intended to facilitate development and accelerate the regulatory process of drugs that address serious unmet needs.² EGFR-mutated lung cancer comprises 15% to 20% of patients with adenocarcinoma,³ and TKIs are the current standard of care for first-line treatment of EGFR-mutated NSCLC.⁴ However, limited options exist for patients who have progressed or acquired resistance, underscoring a critical need for novel therapies beyond the first line.

With the designation, Avenzo Therapeutics, the sponsor, is eligible for more frequent interactions with the FDA for guidance on clinical development, accelerated approval, priority review given fulfillment of criteria, and rolling review of a new drug application, all of which are efforts to expedite the delivery of AVZO-1418 to patients.

"We are excited to receive this [f]ast [t]rack designation from the FDA, underscoring the promise of AVZO-1418, especially for patients with EGFR-[m]utated TKI-[p]retreated NSCLC," said Mohammad Hirmand, MD, chief medical officer of Avenzo Therapeutics, in a news release.¹ "This designation has the potential to help expedite the development of AVZO-1418, which we continue to rapidly advance in [p]hase 1."

About AVZO-1418

AVZO-1418 is a novel bispecific ADC targeting both EGFR and HER3, intended for intravenous administration. Its mechanism of action uses a topoisomerase I payload and is designed using DualityBio’s proprietary Duality Innovative Bispecific Antibody Conjugate platform.⁵ To date, the agent has demonstrated encouraging, broad preclinical activity across multiple solid tumor models, including those that were EGFR resistant, EGFR low, or HER3 resistant.

In May 2025, the FDA cleared the investigational new drug application of AVZO-1418 for the treatment of advanced solid tumors.

AVZO-1418’s safety, tolerability, and preliminary clinical activity are currently under clinical evaluation as monotherapy in a first-in-human, open-label phase 1/2 study (NCT07038343), which launched in June 2025.⁶ The study is recruiting and aims to enroll a total of 430 adult patients with locally advanced or metastatic epithelial solid tumors.

The phase 1 portion is a dose-escalation study that aims to assess AVZO-1418’s safety and tolerability and determine the maximum tolerated dose and recommended phase 2 dose (RP2D) of the agent as monotherapy. With an established RP2D, the phase 2 dose-expansion portion aims to investigate the antitumor activity of the agent as monotherapy and potentially in combination with another agent, pending phase 1 results.

REFERENCES

1. Avenzo Therapeutics granted fast track designation for AVZO-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. Business Wire. November 10, 2025. Accessed November 11, 2025. https://tinyurl.com/2b6kn4hh

2. Fast track. FDA. Updated August 13, 2024. Accessed November 11, 2025. https://tinyurl.com/ms2695jn

3. O'Leary C, Gasper H, Sahin KB, et al. Epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Pharmaceuticals (Basel). 2020;13(10):273. doi:10.3390/ph13100273

4. Zhou F, Guo H, Xia Y, et al. The changing treatment landscape of EGFR-mutant non-small-cell lung cancer. Nature Reviews Clinical Oncology. 2024;22(2):95-116. doi:10.1038/s41571-024-00971-2

5. 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 11, 2025. https://tinyurl.com/4atuhxxx

6. 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 11, 2025. https://clinicaltrials.gov/study/NCT07038343