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Published on: August 15, 2019
First-in-Human Study of OBI-999, a Globo H-Targeting Antibody-Drug Conjugate, in Patients With Advanced Solid Tumors
Apostolia Maria Tsimberidou1, Henry Hiep Vo1, Jennifer Beck1
1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX.
Purpose:
OBI-999 is a novel antibody-drug conjugate comprising the Globo H-targeting antibody (OBI-888) linked to the cytotoxic payload monomethyl auristatin E. OBI-999 demonstrated excellent dose-dependent tumor growth inhibition in breast, gastric, and pancreatic cancer xenograft models as well as a lung cancer patient-derived xenograft model. We conducted a phase I study of OBI-999 monotherapy in patients with advanced cancer (ClinicalTrials.gov identifier: NCT04084366).
Patients And Methods:
OBI-999 was administered intravenously at doses of 0.4, 0.8, 1.2, and 1.6 mg/kg every 21 days as part of a 3 + 3 trial design. Primary end points were the incidence of dose-limiting toxicities and adverse events and determination of the maximum tolerated dose (MTD)/recommended phase II dose.
Results:
Fifteen adult patients were treated. OBI-999 was well tolerated up to 1.2 mg/kg, the maximum tolerated dose. The most common treatment-emergent adverse events were neutropenia and anemia. OBI-999 exhibited nonlinear pharmacokinetics at all doses, with lower clearance at higher doses. The three patients treated at the 1.6 mg/kg dose level developed grade 4 neutropenia during cycles 1 and 2. Five (33.3%) patients had stable disease (SD) including one patient with adenoid cystic carcinoma of the oropharynx with SD for 13 cycles and one patient with gastroesophageal junction adenocarcinoma with SD for eight cycles. OBI-999 was well tolerated; however, dose-dependent, noncumulative neutropenia was dose-limiting.
Conclusion:
The recommended phase II dose was determined to be 1.2 mg/kg once every 3 weeks. A phase II cohort-expansion study is now enrolling patients with pancreatic, colorectal, and other cancers expressing high levels of Globo H.
Insights
OBI-999, a novel antibody-drug conjugate, showed promising results in advanced cancer patients. The recommended Phase II dose is 1.2 mg/kg, with neutropenia as the dose-limiting toxicity.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- OBI-999 is a novel antibody-drug conjugate targeting Globo H, linking OBI-888 to monomethyl auristatin E.
- Preclinical studies demonstrated OBI-999's dose-dependent tumor growth inhibition in various cancer models.
Purpose of the Study:
- To evaluate the safety, tolerability, and maximum tolerated dose (MTD) of OBI-999 monotherapy in patients with advanced cancer.
- To determine the recommended Phase II dose for OBI-999.
Main Methods:
- A Phase I, 3+3 trial design was used, administering OBI-999 intravenously at doses of 0.4, 0.8, 1.2, and 1.6 mg/kg every 21 days.
- Primary endpoints included dose-limiting toxicities, adverse events, and MTD determination.
Main Results:
- OBI-999 was well tolerated up to 1.2 mg/kg (MTD). Common adverse events included neutropenia and anemia.
- Five patients (33.3%) achieved stable disease, with some experiencing prolonged stability.
- Dose-dependent neutropenia was identified as the dose-limiting toxicity.
Conclusions:
- The recommended Phase II dose for OBI-999 is 1.2 mg/kg every 3 weeks.
- A Phase II study is ongoing to evaluate OBI-999 in patients with Globo H-expressing pancreatic, colorectal, and other cancers.
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