60O - A phase Ia study of DNP002, a monoclonal antibody that binds to tumor-associated CEACAM family proteins, in patients with advanced solid tumors: Interim results from dose escalation study

Background

DNP002 is a humanized IgG1 antibody that can kill tumor cells overexpressing CEACAM1/5/6 by antibody-dependent cellular cytotoxicity. CEACAM6 is overexpressed in tumor-associated neutrophils (TANs) including MDSCs, which allows DNP002 to restore the immunosuppressive effect in the tumor microenvironment. We present the preliminary efficacy and safety findings from the interim phase Ia in patients with advanced cancer.

Methods

Eligible patients were aged 18 or older with an ECOG performance status of 0-1 and a history of prior anticancer treatment. Dose escalation cohorts ranged from 0.01 to 1.0 mg/kg and were administered every two weeks using a traditional 3+3 design. The study objectives were to assess safety, preliminary efficacy, pharmacokinetics, immunogenicity, and identifying pharmacodynamic markers.

Results

As of June 26th, 2024, 16 Korean subjects with advanced solid cancer were assigned to four cohorts. At cohort 4 (0.25 mg/kg), two dose-limiting toxicities (DLTs) were observed, leading to the discontinuation of treatment due to grade 5 neutropenic sepsis. Serious adverse drug reactions were neutropenia (12.5%), pneumonia (6.25%), periorbital cellulitis (6.25%), and sepsis (6.25%), which were suspected to be linked to decreased neutrophil count. Tumor assessment was feasible in 12 patients. Regarding the best response, one subject achieved partial response while seven had stable disease. In cohort 2 (0.03 mg/kg), a heavily pre-treated esophageal cancer patient whose tumor had progressed through anti PD-1 inhibitor treatment was enrolled. This patient received 17 doses of DNP002 and experienced a 69% reduction in the sum of tumor sizes compared to baseline, maintaining a partial response for 30 weeks. Additionally, target lesion shrinkage was noted in two patients, and there was a significant increase of activated cytotoxic T cells.

Conclusions

In the first-in-human Phase Ia trial, DLT was observed at 0.25 mg/kg, attributed to neutropenia. However, DNP002 demonstrated tolerability with limited and manageable toxicity and a partial response observed at 0.03 mg/kg. This study is still ongoing to determine the maximal tolerated dose.

Clinical trial identification

NCT06466265.

Editorial acknowledgement

Legal entity responsible for the study

Kumho HT, Inc.

Funding

Kumho HT, Inc.

Disclosure

W. Choi: Financial Interests, Personal, Advisory Role: TTY Biopharm, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Dong-A ST, Bayer. S.Y. Kim: Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Invited Speaker: LG Chem; Financial Interests, Institutional, Research Grant: Roche. G. Ji, K.P. Hong, Y. Kim: Financial Interests, Personal and Institutional, Affiliate: Kumho HT. T.W. Kim: Financial Interests, Institutional, Research Grant: Genentech, Genome Insight. All other authors have declared no conflicts of interest.