Language

English

Publication Date

8-6-2026

Journal

The Oncologist

DOI

10.1093/oncolo/oyag249

PMID

42371780

PMCID

PMC13503030

PubMedCentral® Posted Date

6-29-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: OBI-999 is an antibody-drug conjugate consisting of the Globo H-targeting antibody OBI-888 linked to the cytotoxic payload monomethyl auristatin E. In a dose-escalation study, the OBI-999 recommended phase 2 dose (RP2D) was 1.2 mg/kg every 3 weeks. This dose-expansion study evaluated the efficacy and safety of OBI-999 in patients with pancreatic cancer, colorectal cancer (CRC), or other tumor types ("basket cohort") and tumoral Globo H H-scores ≥100 (NCT04084366).

Patients and methods: Patients were treated at RP2D of OBI-999. We assessed response, progression-free survival (PFS), treatment-emergent adverse events (TEAEs), and pharmacokinetics of OBI-999.

Results: Of 29 patients treated, 23 were evaluable for response. Eight (34.8%) had stable disease): pancreatic cancer, 4 of 7; CRC, 2 of 8; basket cohort, 2 of 8. No objective response was noted. The median time on treatment was 22 days. No association between H-score and tumor size reduction was noted. Median PFS was 3.3 months, 1.3 months, and 1.4 months in the pancreatic, CRC, and basket cohorts, respectively. One patient (3.4%) experienced a serious TEAE related to OBI-999 (febrile neutropenia) that led to discontinuation of OBI-999; the TEAE resolved 3 days after onset. OBI‑999 showed consistent pharmacokinetics with comparable exposure at RP2D across cohorts.

Conclusions: OBI-999 had a favorable safety profile. Although 34.8% of patients had disease stabilization, no objective response was noted, likely owing to inefficient antigen binding, suboptimal systemic exposure at the tolerated dose, and complex tumor biology.

Keywords

Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Antibodies, Monoclonal, Humanized, Immunoconjugates, Neoplasms, Oligopeptides

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.