YS110, an anti-CD26 monoclonal antibody, was found to be safe in a Phase 1 clinical trial of 33 patients with CD26-positive solid tumors. Though these are very early results, the drug appears to have stabilized tumors in 13 of the patients.
CD26 is a protein usually found on the surface of normal white blood cells called lymphocytes, and it normally plays a role in immune reactions. However, it is also found on some malignant tumors that are not growing from lymphocytes. CD26 appears to help cancer formation along in these tumors. YS110 is made with an antibody that blocks CD26.
Of the 33 patients in the trials, 22 had mesothelioma. Ranging in age from 18 to 80 years old, they had locally advanced, inoperable or refractory solid tumors — or those which do not improve with chemotherapy or radiotherapy — with CD26 on the surface of their cells. Besides mesothelioma patients, the trial also included those with non-small-cell lung carcinoma, renal cell carcinoma (RCC) or hepatocellular carcinoma (liver cancer).
All patients had one or more adverse events; the most frequently reported such events that were not necessarily caused by YS110 were abnormal physical weakness or lack of energy, and worsening of prior conditions. Researchers reported 113 adverse drug reactions (ADRs) — possibly related to YS110 — in 30 of the 33 patients. These included low-grade lack of energy (30.3% of the total), allergic reaction (27.3%), nausea (15.2%), flushing (15.2%), chills (12.1%) and fever (12.1%).
YS110 was generally found to be safe, and treatment of most ADRs was possible. Two participants with allergies could not tolerate YS110, however.
Out of 26 cases assessed for efficacy (19 cases of mesothelioma, six cases of RCC, and one case of urinary tract carcinoma), a progression-free survival of 184–399 days was seen in seven patients (five cases of mesothelioma and two cases of RCC). Progression-free survival is the length of time during and after the treatment that a patient lives with the disease but it does not get worse.
“YS110 is the first, and currently the only, CD26-directed mAb in clinical trial,” researchers stated. “This [first-in-human] study demonstrates that YS110 therapy exhibits a favorable safety profile and results in encouraging disease stabilization in heavily pretreated CD26-positive malignant pleural mesothelioma (MPM) or RCC patients who had previously progressed on conventional standard therapies.”
Researchers added that their study showed that YS110 therapy is generally well tolerated up to 6 mg kg−1 Q1W, which has been defined as the recommended Phase 2 dose. This results in encouraging disease stabilization in a number of patients with advanced/refractory CD26-expressing cancers, they said, suggesting that “further clinical development of YS110, such as its use as part of combination therapies with other antineoplastic agents, is warranted.”