Investigational anti-CD137 monoclonal IgG4 antibody ADG106 showed no concerning safety signals in the phase 1, open-label, dose-escalation, multicenter trial recently reported at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. A preliminary result from a single patient suggests the agent may also have clinical activity.

“ADG106 targets a unique epitope of CD137 with novel mechanism of actions for CD137 agonism, CD137 antagonism, and potent cross-linking via FcgRIIb,” the study authors wrote. “The broad cross-reactivity of ADG106 with mouse, rats, monkey, and human enables robust translational studies using syngeneic tumor models with intact immune system.”

The trial (ClinicalTrials.gov Identifier: NCT03707093) is enrolling patients with advanced or metastatic solid tumors and/or relapsed/refractory non-Hodgkin lymphoma, and 10 patients have been enrolled so far as of July 11, 2019. Patients were enrolled across 5 dosing cohorts for ADG106 (0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg) and evaluated for safety.

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At the time of study analysis, safety evaluations were available for only 7 patients: 1 patient at dose 0.03 mg/kg, 1 patient at dose 0.1 mg/kg, 1 patient at dose 0.3 mg/kg, and 4 patients at 1 mg/kg. The 7 patients received between 1 and 8 cycles (median, 3 cycles).  

The following were the most frequently reported treatment-emergent adverse events (TEAEs): arthralgia (43%), decreased appetite (29%), diarrhea (29%), hypothyroidism (29%), and vomiting (29%).

No drug-related serious adverse events (SAEs) or dose-limiting toxicities (DLTs) were reported. However, 4 patients had at least 1 grade 3 TEAEs, one of which was grade 3 anorexia that occurred in a patient who received the lowest dose; the event was believed to be related to ADG106. One patient who received the 1 mg/kg dose had grade 3 tachycardia, which was considered a SAE but unrelated to ADG106. No grade 4 TEAEs were reported.

One patient with refractory stage IV follicular lymphoma who was refractory to multiple prior therapies had tumor shrinkage and lower standardized uptake value scores, suggesting possible clinical activity with ADG106.

“ADG106 demonstrated excellent safety and tolerability profiles at doses up to 1 mg/kg and currently 3 mg/kg is being explored,” the study authors wrote. 

Disclosure: The trial was sponsored by Adagene Inc, a biotech company. 

Reference

  1. Tolcher A, Karim R, Rosas C, et al. A phase 1, first-in-human, dose-escalation study of ADG106, a fully human anti-CD137 agonistic antibody, in subjects with advanced or metastatic solid tumors and/or relapsed/refractory non-Hodgkin lymphoma. Presented at: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; October 26–30, 2019: Boston, Massachusetts. Abstract A082.