A MYC inhibitor appears tolerable and active in patients with advanced solid tumors that progressed on standard care, a first-in-human trial suggests.
The pan-MYC inhibitor OMO-103 was associated with mild adverse events. Although the drug did not produce any responses, 47% of evaluable patients maintained stable disease.
These results were presented at the 2022 EORTC-NCI-AACR Symposium by Elena Garralda, MD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain.
Dr Garralda said OMO-103 is the first direct MYC inhibitor, it acts against the whole MYC family, and it has cell-penetrating properties. The aim of this first-in-human trial (ClinicalTrials.gov Identifier: NCT04808362) was to evaluate the tolerability of OMO-13 and establish the recommended phase 2 dose.
The study included 22 patients with advanced solid tumors that had progressed after standard care. The most common cancer types were pancreatic ductal adenocarcinoma (n=8) and colorectal cancer (n=7). One patient each had sarcoma, small-cell lung cancer, non-small cell lung cancer, pleuromesothelioma, salivary gland carcinoma, triple-negative breast cancer, and ovarian cancer.
At baseline, the median age was 60.5 years, and 50% of patients were women. Patients had an ECOG performance status of 0 or 1, and they had received a median of 4 (range, 2-12) prior lines of therapy.
The patients received OMO-103 at 6 doses ranging from 0.48 mg/kg to 9.72 mg/kg. OMO-103 was administered as a weekly intravenous infusion.
OMO-103 was tolerable, according to Dr Garralda. There was 1 grade 3 treatment-related adverse event (TRAE), which was an infusion-related reaction. The most common TRAEs were infusion-related reactions, back pain, anemia, and asthenia.
The 6.48 mg/kg dose was established as the recommended phase 2 dose. There was 1 dose-limiting toxicity, which was grade 2 pancreatitis.
There were 17 patients evaluable for efficacy, and none experienced a partial or complete response. However, 8 had stable disease.
There were several cases of long-term stable disease in patients who had not responded well to previous treatments, Dr Garralda said. She highlighted 1 patient with pancreatic cancer who was on OMO-103 for 4 months and 1 patient with sarcoma who was on OMO-103 for more than 6 months, both of whom had derived little benefit from prior therapy. In addition, 1 patient with salivary gland carcinoma is still on OMO-103 after 15 months.
A biomarker analysis suggested that low levels of 4 cytokines — CD26E, IL-8, MIP-1β, and GM-CSF — could potentially predict response to OMO-103. Patients with stable disease tended to have lower levels of these cytokines at baseline, when compared with patients who had progressive disease.
Dr Garralda noted that part 2a of this study is currently being planned.
Disclosures: This study was supported by Peptomyc S.L. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Garralda E, Moreno V, Alonso G, et al. Dose escalation study of OMO-103, a first in class pan-MYC-inhibitor in patients (pts) with advanced solid tumors. EORTC-NCI-AACR Symposium 2022. October 26-28, 2022. Abstract 7.