Iambic Therapeutics has successfully completed dose escalation in its Phase 1/1b clinical trial evaluating IAM1363, a selective and brain-penetrant small molecule inhibitor of wild-type and oncogenic mutant HER2. The San Diego-based clinical-stage company announced that it is advancing two well-tolerated doses into the dose optimization phase of the study.
Study Design and Patient Population
The Phase 1/1b trial (NCT06253871) is an open-label, multi-center, dose escalation and dose optimization study designed to evaluate tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of IAM1363 in patients with advanced HER2 cancers. Patients enrolling into dose optimization include those with HER2-altered cancers and brain metastases, any advanced cancer harboring a HER2 TKD (tyrosine kinase domain) mutation, and advanced HER2-amplified non-small cell lung cancer.
The study currently has multiple sites in the US and will expand to the EU, UK and APAC regions. "We are very encouraged by the progress of the study and the pace at which we arrived at what we believe are potentially efficacious dose levels," said Neil Josephson, M.D, Iambic's Chief Medical Officer.
Addressing Unmet Medical Need
The advancement of IAM1363 addresses a significant unmet medical need, particularly for patients with brain metastases. "Patients entering this study, particularly those with brain metastases, have few available treatment options," said Andrae Vandross, M.D., who leads the Phase 1 clinical trial group at NEXT Oncology in Austin, TX, a IAM1363 study site. "Our focus is on identifying important potential advances for these individuals and to look at novel approaches that may provide a therapeutic benefit."
Preclinical Profile and Differentiation
IAM1363, designed with Iambic's AI-Drug Discovery platform, is highly differentiated by its target selectivity, brain-penetrance, pan-mutant activity, and tumor enrichment. In preclinical studies, the compound has demonstrated over 1000-fold selectivity for HER2 compared to EGFR, a promising pharmacokinetic and safety profile, preferential tumor enrichment, and penetrance of the central nervous system.
In HER2 tumor models, including intracranial tumor models, IAM1363 has demonstrated favorable efficacy and tolerability compared to benchmark tyrosine kinase inhibitors and HER2-targeted antibodies, and antibody-drug conjugates.
Therapeutic Flexibility and Future Plans
According to Dr. Josephson, "IAM1363 provides us considerable flexibility to evaluate the treatment as a monotherapy and in combination with other targeted therapies as we look to address a broad range of HER2-altered cancers."
Iambic intends to present data from the study at the European Society for Medical Oncology Congress (ESMO) in October 2025. The company has commenced the second part of the study to evaluate safety and preliminary efficacy of IAM1363 as a monotherapy against advanced HER2 cancers.
