October 26, 2026 | OncLive Staff
DECK: IBI3001, an EGFR/B7-H3 bispecific antibody-drug conjugate, was tolerable and elicited responses in a phase 1 trial in advanced solid tumors.
IBI3001 was tolerable and elicited responses in patients with advanced solid tumors, according to data from a first-in-human phase 1 trial (NCT06349408) presented at the 2026 ESMO Congress.¹
Among patients with at least 1 post-baseline tumor assessment (n = 53), the objective response rate (ORR) was 30.2% (95% CI, 18.3%-44.3%), and the disease control rate (DCR) was 88.7% (95% CI, 77.0%-95.7%). At a dose of 6 mg/kg (n = 27), the ORR was 25.9% (95% CI, 11.1%-46.3%), and the DCR was 81.5% (95% CI, 61.9%-93.7%); at a dose of 8 mg/kg (n = 20), the ORR was 45.0% (95% CI, 23.1%-68.5%), and the DCR was 100.0% (95% CI, 83.2%-100%). No patient experienced a complete response, and 12 of the 16 responders had their response confirmed as of the data cutoff.
Among patients with EGFR-mutant non–small cell lung cancer (NSCLC; n = 16), the ORR was 31.3% (95% CI, 11.0%-58.7%), the DCR was 93.8% (95% CI, 69.8%-99.8%), and the median progression-free survival (PFS) was 7.7 months (95% CI, 5.5-not estimable). Among patients with pancreatic ductal adenocarcinoma (PDAC; n = 15), the ORR was 15.4% (95% CI, 1.9%-45.4%), the DCR was 92.3% (95% CI, 64.0%-99.8%), and the median PFS was 6.9 months (95% CI, 2.1-11.2).
What was the design of the first-in-human phase 1 trial of IBI3001 in advanced solid tumors?
IBI3001 is a bispecific antibody-drug conjugate (ADC) that binds EGFR and B7-H3 and delivers exatecan, a topoisomerase I inhibitor, at a drug-to-antibody ratio of 4. Laboratory studies have indicated a potent bystander effect and antitumor activity in models with differing EGFR and B7-H3 levels, along with favorable stability and safety.
The phase 1 trial is multicenter, multiregional, and open label, with sites in Australia, China, and the United States.2 Across dose-escalation and backfill cohorts (backfill was limited to selected tumor types), patients received IBI3001 intravenously every 3 weeks at 1 mg/kg (n = 1), 3 mg/kg (n = 3), 6 mg/kg (n = 28), 8 mg/kg (n = 22), or 10 mg/kg (n = 3).1 Dose escalation used a modified continual reassessment method and a Bayesian logistic regression model, and dose-limiting toxicities (DLTs) were assessed during the first 21 days. Eligible adult patients had locally advanced, unresectable, or metastatic solid tumors for which standard therapy was unavailable, no longer effective, or unacceptable; at least 1 evaluable lesion per RECIST 1.1 criteria; and an ECOG performance status of 0 or 1. Treatment continued until progression, intolerance, consent withdrawal, or the completion of 24 months of therapy. The primary end points were safety; DLTs; and determining the recommended phase 2 dose for dose escalation and efficacy for dose expansion.
A total of 57 patients were treated. The median age was 63.0 years (range, 42-77), 57.9% of patients were male, 70.2% of patients were enrolled in China, 77.2% of patients had an ECOG performance status of 1, and 89.5% of patients had stage IV disease. The most common tumor types were NSCLC (36.8%) and PDAC (26.3%), followed by small cell lung cancer (SCLC; 14.0%) and colorectal cancer (10.5%). Patients had received a median of 2.0 prior lines of therapy (range, 1-7), and 78.9% of patients had received at least 2 prior lines. The median follow-up was 8.25 months (range, 0.3-17.3), and the median treatment duration was 24.0 weeks (range, 3-78).
What was the efficacy of IBI3001 in SCLC and squamous cell carcinomas?
Among patients with SCLC (n = 8), the ORR was 62.5% (95% CI, 24.5%-91.5%), and the DCR was 100.0% (95% CI, 63.1%-100%). Among patients with squamous cell carcinoma of the head and neck or esophagus (n = 5), the ORR was 60.0% (95% CI, 14.7%-94.7%), and the DCR was 100.0% (95% CI, 47.8%-100%).
What was the safety profile of IBI3001 in patients with advanced solid tumors?
Among all treated patients (n = 57), TRAEs of any grade occurred in 93.0% and grade 3 or higher TRAEs were reported in 47.4%, including 35.7% at the 6-mg/kg dose (n = 28) and 59.1% at 8-mg/kg dose (n = 22). Serious TRAEs occurred in 21.1% of patients. TRAEs led to treatment interruption in 40.4% of patients, dose reduction in 17.5% of patients, and treatment discontinuation in 1.8% of patients. Five patients (8.8%) experienced a treatment-emergent adverse effect leading to death; none were treatment related.
Four DLTs were observed. In the dose-escalation portion, 1 of 6 patients at the 8-mg/kg dose had grade 3 febrile neutropenia, and 1 of 3 patients at 10-mg/kg dose had grade 4 decreased platelet count and grade 3 hyperbilirubinemia. In the backfill portion, 2 of 20 patients at the 6-mg/kg dose had grade 4 decreased platelet count and grade 3 febrile neutropenia. The investigators noted that all DLTs were managed effectively.
The most frequent TRAEs were hematologic, which the investigators attributed mainly to the IBI3001 payload. Anemia occurred in 64.9% of patients (grade ≥ 3, 24.6%), decreased neutrophil count in 52.6% of patients (grade ≥ 3, 19.3%), decreased white blood cell count in 49.1% of patients (grade ≥ 3, 12.3%), and decreased platelet count in 33.3% of patients (grade ≥ 3, 10.5%); any-grade decreased appetite (42.1%) and nausea (40.4%) were the most frequent nonhematologic TRAEs. Premedication was not given to mitigate hematologic TRAEs. One patient had grade 2 pneumonitis.
References
- Hu Y, Zhang F, Sen S, et al. Safety and efficacy of IBI3001, an anti-EGFR/B7H3 bispecific ADC, in patients (pts) with advanced solid tumors: results of a multi-regional phase 1 study. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract 1001O.
- IBI3001 in participants with unresectable, locally advanced or metastatic solid tumors. ClinicalTrials.gov. Updated September 25, 2026. Accessed October 24, 2026. https://clinicaltrials.gov/study/NCT06349408
