Iambic's AI-Designed HER2 Drug IAM1363 Shows Durable Responses at ESMO 2026
Iambic Therapeutics has presented updated Phase 1/1b data for IAM1363, a selective, brain-penetrant HER2 tyrosine kinase inhibitor, showing durable anti-tumor activity and intracranial responses in heavily pretreated patients. According to the company, the drug was discovered with its AI platform and reached clinical development in approximately two years.
- Iambic presented updated IAM1363 Phase 1/1b data at ESMO 2026 in Madrid on October 23, 2026.
- At ≥960 mg QD, 36% (19/53) had a partial response by RECIST v1.1, and 41% (9/22) had an intracranial partial response by modified RANO-BM.
- At 960 mg QD (n=68), grade 3 TRAEs and TRAEs leading to dose modifications were each 5.9%, with no grade 4 or 5 TRAEs.
- Three HER2-positive breast cancer participants previously treated with T-DXd and tucatinib had confirmed intracranial partial responses.
- According to Iambic, IAM1363 went from project initiation to clinical development in approximately two years.
Who was treated and what the trial covers
The data were shown in a poster at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid on October 23, 2026. Iambic (Nasdaq: IAM) announced the results on October 26. The data cutoff was August 31, 2026.
As of that date, 122 participants had received IAM1363 across Parts 1-4 of the study. Of these, 103 were treated with monotherapy at doses of ≥960 mg, and 68 received the recommended dose of 960 mg once daily (QD). The population was heavily pretreated, with a median of three prior regimens in the metastatic setting. According to Iambic, 61% had received prior trastuzumab deruxtecan (T-DXd) and 36% prior tucatinib. Breast cancer (38%) and non-small cell lung cancer (NSCLC) (19%) were the most common tumor types, and 44% of participants had central nervous system (CNS) metastases.
The trial (NCT06253871) is open-label and multicenter. It evaluates safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy in participants with HER2-altered advanced cancers. Dose escalation (Part 1) and dose optimization (Part 2) are completely enrolled. Monotherapy expansion cohorts at 960 mg (Part 3) and combination cohorts (Part 4) are open to enrollment at sites in the U.S., Europe and Asia.
Systemic and intracranial results
In participants with targetable HER2 alterations dosed at ≥960 mg QD, the best overall response by RECIST v1.1 was:
- partial response in 36% (19/53)
- stable disease in 38% (20/53)
- progressive disease in 26% (14/53)
For intracranial activity, measured by modified RANO-BM, the best overall response was partial response in 41% (9/22), stable disease in 55% (12/22) and progressive disease in 5% (1/22).
Iambic reports that more than half of participants dosed at 960 mg QD remain on study treatment. Responses are ongoing beyond 12 months in a participant with HER2-mutant NSCLC who had received prior T-DXd, and in a participant with HER2-mutant renal cell cancer. A separate participant with HER2-mutant NSCLC has maintained disease control for more than 10 months.
Responses were seen across HER2-positive, HER2-mutant and HER2-amplified cancers, including breast cancer, NSCLC, biliary tract cancer, gastroesophageal adenocarcinoma and renal cell cancer. Three participants with NGS-detected HER2-amplified cancers had durable responses.
Three participants with HER2-positive breast cancer, all previously treated with T-DXd and tucatinib, achieved confirmed intracranial partial responses per RANO-BM, and all remain on treatment. One of them had more than 50 brain metastases and had received seven different HER2-directed agents.
Tolerability profile
The company describes IAM1363 monotherapy as generally well tolerated. Among the 68 participants dosed at 960 mg QD, few experienced grade 3 treatment-related adverse events (TRAEs) or TRAEs that led to dose modifications, at 5.9% for each. None experienced a grade 4 or 5 TRAE.
Across all participants dosed at ≥960 mg QD (n=103), most treatment-emergent adverse events were low grade. The most common of any grade were diarrhea (59%), nausea (53%) and vomiting (49%). There were no Grade 4 TEAEs and no Grade 5 TRAEs.
What the company says and what comes next
"Last year at ESMO we shared the first clinical data for IAM1363," said Tom Miller, PhD, Co-Founder and CEO of Iambic, adding that the update shows the data set maturing in "durability, higher rate of best overall response, and consistent tolerability at the recommended dose."
Chief Medical Officer Neil Josephson, MD, said the data support continued development of IAM1363. He pointed to the intracranial responses in HER2-positive breast cancer patients previously treated with T-DXd and tucatinib, noting that patients with brain metastases have limited options. Iambic plans to keep evaluating IAM1363 as a monotherapy and in combination with standard of care therapies.
The results come with caveats. Iambic itself notes that data from an ongoing early-phase trial with a limited number of participants may change as the study continues and may not be predictive of results in later trials. For now, the findings are early evidence from a Phase 1/1b study, while the company positions the program as an example of its AI-driven discovery platform moving a candidate into the clinic quickly.
