Findings from part A of the phase 2/3 RINGSIDE trial reveal AL102 to demonstrate favorable safety in patients with desmoid tumors.
AL102 was found to be well tolerated with favorable safety in patients with desmoid tumors, according to interim findings from part A of the phase 2/3 RINGSIDE trial (NCT04871282).1
MRI scans showed that treatment with the selective, potent, oral gamma-secretase inhibitor AL102 at varying doses resulted in tumor shrinkage in 13 of the patients who were evaluable at 16 weeks. Additionally, 1 patient experienced an unconfirmed partial response per RECIST v1.1 criteria at week 16.
At all dose levels, AL102 was well tolerated at all of the examined dose levels with no dose-limiting toxicities observed with the agent. There were no grade 4 or 5 toxicities which occurred with AL102, and the most common grade 1 or 2 adverse effects included diarrhea, fatigue, skin rash, and nausea.
“We are very excited with the interim data from part A of the RINGSIDE study, although early, demonstrating initial substantial antitumor activity for AL102 as a single agent as measured by MRI scans,” stated Roni Mamluk, PhD, chief executive officer of Ayala Pharmaceuticals, Inc., in the press release. “We are also encouraged with the safety data showing that AL102 appears to be well tolerated. We look forward to presenting a more advanced and comprehensive data set at a medical meeting later in the year.”
RINGSIDE is a randomized, multicenter study, which examined the safety, tolerability, and efficacy of AL102 in adult and adolescent patients with desmoid tumors. The target enrollment was 192 patients split between 2 portions of the trial, the dose-finding phase (part A) and the dose-expansion phase (part B).
Enrollment for part A was completed in February 2022. This cohort of patients included 42 patients with desmoid tumors received single-agent AL102 at 1 of the following 3 doses, including 1.2 mg daily, 2 mg on a 2-days-on, 5-days-off schedule, or 4 mg on a 2-days-on, 5-days-off schedule. Activity of the AL102 was evaluated by change in tumor volume and response per RECIST v1.1 criteria according to investigator assessment.
Those enrolled in part A of the trial are eligible for enrollment in the open-label extension study at the selected dose. In this portion of the study, investigators will evaluate for long-term safety and efficacy.
The randomized, double-blind, placebo-controlled part B portion of the trial is anticipated to begin after a dose for the agent has been selected in part A. A total of 156 patients with progressive desmoid tumors are expected to be enrolled within this portion of the study. Patients will be randomized to receive either AL102 or placebo.
The primary end point is progression-free survival with secondary end points including objective response rate, duration of response, and patient-reported quality of life measures.
To be eligible for enrollment in part A of the study, patients must be 18 years of age or older with histologically, confirmed disease, at least 1 measurable lesion per RECIST v1.1. Patients must also have disease progression assessed locally by an investigator. For part B of the study, patients must be aged 12 or older with a histologically confirmed desmoid tumor, and measurable disease per RECIST v1.1.
“RINGSIDE is the first study to investigate AL102 exclusively in desmoid tumor patients and it has been designed to evaluate a range of different doses and dose schedules,” added Gary Gordon, MD, PhD, chief executive officer of Ayala, added in a release. “Successful management of this disease will likely require chronic treatment and 1 of the key goals of our development program is to understand the optimal balance between efficacy, safety, and patient acceptability. We are encouraged by the early but very promising efficacy data and emerging favorable [safety] profile for AL102 reported in these interim results.”