The problem

KRAS is the most frequently mutated oncogenic driver in non-squamous NSCLC, found in roughly a quarter to a third of cases. The first approved KRAS drugs targeted the G12C variant. KRAS G12D, present in about 4% of NSCLC, has remained without an approved selective therapy, leaving these patients with limited targeted options.

Why it's hard

G12D is a difficult target. It lacks the reactive pocket that made G12C druggable, and any inhibitor must distinguish the mutant protein from wild-type KRAS to avoid broad toxicity.

How AVN-101 is designed

AVN-101 is an oral, brain-penetrant small molecule engineered with PenSelect™ chemistry to:

• bind the G12D mutant form of KRAS with high selectivity over wild-type,
• maintain activity against anticipated downstream resistance, and
• achieve central nervous system exposure, with the aim of addressing brain metastases, a frequent site of NSCLC spread.

Preclinical program

AVN-101 has been characterized in preclinical models of KRAS G12D-mutant cancer, with central nervous system exposure as a core design objective. Preclinical findings will be reported through peer-reviewed publications and scientific congresses.

The TRAVERSE-1 trial

TRAVERSE-1 is a first-in-human, open-label Phase 1 study evaluating the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of AVN-101 in adults with KRAS G12D-mutant advanced NSCLC and other solid tumors. The study is in dose escalation.

AVN-101 is an investigational therapy that has not been approved by the FDA, EMA, or any other regulatory authority. Its safety and efficacy have not been established.

The problem

EGFR mutations drive roughly 15% of NSCLC in Western populations and a substantially higher share in East Asian populations. Third-generation inhibitors such as osimertinib are now standard of care, yet most patients eventually relapse, frequently through C797S-class resistance mutations for which no targeted therapy is approved. When the disease returns, options narrow sharply.

How AVN-201 is designed

AVN-201 is an oral, brain-penetrant fourth-generation EGFR inhibitor engineered to:

• remain active against C797S and common compound resistance mutations that defeat earlier-generation drugs,
• preserve selectivity over wild-type EGFR, with the aim of limiting the rash and gastrointestinal toxicity associated with broad EGFR inhibition, and
• penetrate the central nervous system, a common site of EGFR-mutant relapse.

Preclinical program

AVN-201 has been characterized in preclinical resistance models, with activity against C797S-class resistance and CNS exposure as design objectives. Preclinical findings will be reported through peer-reviewed publications and scientific congresses.

The RECLAIM-1 trial

RECLAIM-1 is a first-in-human, open-label Phase 1 study of AVN-201 in adults with EGFR-mutant advanced NSCLC whose disease has progressed on prior EGFR tyrosine kinase inhibitor therapy. The study is in dose escalation.

AVN-201 is an investigational therapy that has not been approved by the FDA, EMA, or any other regulatory authority. Its safety and efficacy have not been established.

The problem

HER2 (ERBB2) alterations occur in roughly 2 to 4% of NSCLC, most commonly as exon 20 insertions. Available approaches can be limited by toxicity driven by off-target inhibition of wild-type EGFR, and by inadequate control of disease in the brain.

How AVN-301 is designed

AVN-301 is an oral, brain-penetrant small molecule engineered to:

• selectively target HER2 exon 20 insertion variants,
• spare wild-type EGFR, with the aim of improving tolerability, and
• reach the central nervous system.

Preclinical program

AVN-301 has been characterized in preclinical models of HER2 exon 20-insertion NSCLC, with selective target engagement and CNS exposure as design objectives. Preclinical findings will be reported through peer-reviewed publications and scientific congresses.

The MERIDIAN-1 trial

MERIDIAN-1 is a first-in-human, open-label Phase 1 study evaluating AVN-301 in adults with HER2-altered advanced NSCLC. The first patient has been dosed and the study is enrolling.

AVN-301 is an investigational therapy that has not been approved by the FDA, EMA, or any other regulatory authority. Its safety and efficacy have not been established.

Patients & clinical trials

Finding a trial.

If you or a loved one has advanced lung cancer, the best first step is to talk with your own cancer doctor. They can tell you whether a study might be a fit. You can also look up our studies on ClinicalTrials.gov, a free public website run by the U.S. National Institutes of Health.

A few terms, in plain language

Reporting a side effect

To report a suspected side effect related to an Aerivon medicine, contact our medical information team at medinfo@aerivon.eu. If you are in a trial, also tell your study doctor right away.