First Phase of Recruitment Complete in Phase 2/3 Study of Targeted Therapy for Desmoid Tumors

A cohort of patients with desmoid tumor has met its target enrollment in part A of the phase 2/3 RINGSIDE clinical trial of AL102, according to an announcement by Ayala Pharmaceuticals, Inc.¹

Currently, there are no FDA-approved systemic therapies available for the treatment desmoid tumors. However, considering that desmoid tumors have the tendency to harbor mutation in the β-catenin oncogene CTNNB1 or the tumor suppressor gene adenomatous polyposis coli that activate the WNT pathway, investigators hypothesized that AL102 may be a beneficial drug.²

AL102 is a potent, selective, oral gamma-secretase inhibitor of Notch. In a 2021 case study of 2 patients, AL102 achieved a partial response in both patients with a duration of response of 8.6+ yeara in 1 patient and 2.6+ years in the other. Treatment also achieved tumor shrinkage in 1 patient. Investigators of the case study recommended further evaluation of the agent in patients with desmoid tumors who are ineligible for surgery or are refractory to or recurred after prior therapies.^1,2

RINGSIDE (NCT04871282) is a randomized, multicenter study, which had a target enrollment of 192 patients split between the dose-finding phase (part A) and the dose-expansion phase (part B). During part A, arms will be administered AL102 at 1.2 mg to 4 mg daily. Patients in part B will receive the recommended phase 2 dose of the agent in the experimental arm or matching placebo in the comparator arm.³

The primary end point of the study is progression-free survival, and the secondary end points include overall response rate, duration of response, and patient-reported outcomes. With the primary and secondary end points, the goal of RINGSIDE is to evaluate the safety, tolerability, and tumor volume by MRI at 16 weeks in patients with desmoid tumors.

Patients are eligible to enroll in part A given they are 18 years of age or older with histologically. Confirmed disease, at least 1 measurable lesion per RECIST v1.1. patients are also required to have disease progress assessed locally by an investigator.

Those excluded from the part A of the study are patients diagnosed with a malignancy in the past 2 years, as well as those with an ECOG performance of 2 or higher, abnormal organ and morrow function, abnormal electrocardiogram, active infection, or select gastrointestinal and cardiac comorbidities that may interfere with treatment.

Patients ages 12 or older may be included in part B of the study given they have a histologically confirmed desmoid tumor, and measurable disease per RECIST v1.1.

“Completion of enrollment in Part A of the RINGSIDE trial is an important milestone in our AL102 clinical program for desmoid tumors,” said Roni Mamluk, PhD, chief executive officer of Ayala, in a press release.¹ “Part A will help us determine the optimal dose for the randomized portion of the study, we will be looking for safety and signs of anti-tumor activity based on MRI. We are extremely grateful to the patients who are participating, and we look forward to sharing top line data around mid-year.”

_References:

_{1. Ayala Pharmaceuticals announces completion of enrollment in part A of RINGSIDE, a pivotal phase 2/3 study of al102 in desmoid tumors. News release. February 23, 2022. Accessed February 24, 2022. https://bit.ly/3JLYhIS}

_{2. Chan D, Kaplan J, Gordon G, et al. Activity of the gamma secretase inhibitor al101 in desmoid tumors: a case report of 2 adult cases. Curr Oncol. 2021;28(5):3659-3667. doi: 10.3390/curroncol28050312.}

_{3. A study of AL102 in patients with progressing desmoid tumors (RINGSIDE). Clinicaltrials.gov. Accessed February 24, 2022. https://bit.ly/3t8i4f1}