AL102 Monotherapy Demonstrates Early Antitumor Activity in Desmoid Tumors

Roni Mamluk, PhD

Interim findings from part A of the phase 2/3 RINGSIDE trial (NCT04871282) indicated that the selective oral gamma-secretase inhibitor, AL102, was found to have favorable tolerability and early antitumor activity in patients with desmoid tumors.¹

MRI scans showed that the majority of the 13 patients who received AL102 at varying doses and had reached the 16-week time point experienced reductions in tumor size with the agent. Moreover, at week 16, 1 patient experienced an unconfirmed partial response per RECIST v1.1 criteria.

Additionally, AL102 was found to be well tolerated at all dose levels examined. Notably, no dose-limiting toxicities were reported with the agent, and no grade 4 or 5 toxicities occurred. The most common adverse effects experienced with AL102 included diarrhea, fatigue, skin rash, and nausea and they were grade 1 or 2 in severity.

“We are very excited with the interim data from par A of the RINGSIDE study, although early, demonstrating initial substantial antitumor activity for AL102 as a single agent as measured by MRI scans,” Roni Mamluk, PhD, chief executive officer of Ayala Pharmaceuticals, Inc., stated in a 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.”

For the RINGSIDE trial, investigators set out to examine the safety, tolerability, and efficacy of AL102 in adult and adolescent patients with desmoid tumors. Part 1 of the trial utilized an open-label design, and up to 42 patients were enrolled.

To be eligible for enrollment, patients were required to be at least 18 years of age, have a histologically confirmed desmoid tumor by local pathologist, disease progression per investigator assessment, and at least 1 measurable lesion.² They also needed to meet 1 of the following criteria: be treatment naïve or have recurrent or refractory disease following at least 1 line of therapy including surgery, radiation, or systemic treatment.

Enrollment to part A was completed in February 2022, and participants received single-agent AL102 at 1 of the following 3 doses: 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. The activity of the agent was examined by change in tumor volume and response per RECIST v1.1 criteria and investigator assessment.

Those in part A of the trial will be eligible to participate on the open-label extension study at the selected dose, and investigators will evaluate for long-term safety and efficacy. “The results from part A will be used to determine the dose of AL102 to be evaluated in part B of RINGSIDE, the randomized portion of the study, which Ayala is on track to initiate in the third quarter of 2022,” Mamluk added in the press release.

Part B of the trial will be double-blin d and placebo-controlled and is expected to begin immediately after a dose for the agent has been selected in part A. This portion of the research is anticipated to enroll up to 156 patients with progressive desmoid tumors.

These patients will be randomized to receive either AL102 or placebo. Furthermore, the primary end point will be progression-free survival, and key secondary end points will comprise objective response rate, duration of response, and patient-reported quality of life measures.

“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,” 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.”

References

1. Ayala Pharmaceuticals announces interim data from part A of the phase 2/3 RINGSIDE trial of AL102 in desmoid tumors. News release. Ayala Pharmaceuticals, Inc. July 5, 2022. Accessed July 6, 2022. https://bit.ly/3ura76c
2. A study of AL102 in patients with progressing desmoid tumors (RINGSIDE). ClinicalTrials.gov. Updated June 10, 2022. Accessed July 6, 2022. https://clinicaltrials.gov/ct2/show/NCT04871282