FDA Grants Fast Track Designation to AL102 for Progressing Desmoid Tumors

FDA

The FDA has granted a fast track designation to AL102 for the treatment of patients with progressing desmoid tumors, according to an announcement from Ayala Pharmaceuticals.¹

Interim data from part A of the pivotal phase 2/3 RINGSIDE trial (NCT04871282) presented at the 2022 ESMO Congress showed that AL102 elicited responses and tumor shrinkage in patients with desmoid tumors.^2,3 Among patients treated at all doses who underwent 2 or more MRIs (n = 12), 1 patient had a partial response (PR) at week 16 that was confirmed at week 28, 2 patients had unconfirmed PRs at week 28, and 1 patient experienced an unconfirmed PR at week 40.² Continuous volume reduction was observed over time in all patients who underwent 2 or more MRIs.³

Specifically at week 16 for evaluable patients treated at the selected dose of 1.2 mg of AL102 once daily (n = 9), 1 patient achieved a confirmed PR at week 28, 8 patients had stable disease, and 7 experienced tumor reduction.³

“We are pleased to receive FDA fast track designation for AL102 in progressing desmoid tumors, which we believe reinforces the large unmet medical need for patients with this serious disease. This designation holds important advantages that may expedite the development and regulatory review of AL102,” Roni Mamluk, PhD, chief executive officer of Ayala, stated in a press release. “We are very encouraged by the emerging body of clinical data supporting AL102 and, if approved, believe that this product could have a meaningful impact on patients’ lives.”

AL102 is a potent, selective, oral gamma-secretase inhibitor that could represent a potential treatment option for patients with unresectable, recurrent or progressive desmoid tumors, who currently have no FDA-approved systemic therapies.

The global, multicenter, randomized RINGSIDE trial is evaluating the efficacy, safety, and tolerability of AL102 in patients with desmoid tumors. Thus far, 42 patients have been enrolled to receive 3 different doses of AL102. Patients who enrolled in part A will be eligible to participate in an open-label extension study in part B at the selected dose of 1.2 mg of AL102 daily.

The study is enrolling patients who are at least 18 years old with relapsed/refractory or treatment-naïve desmoid tumors who experienced disease progression defined as at least a 10% unidimensional growth within 18 months or desmoid tumor–related pain requiring non-opioid medication.²

In part A of the trial, patients are randomly assigned to 1.2 mg of AL102 per day, 4 mg of AL102 twice per week on a 2-days-on, 5-days-off schedule, or 2 mg of AL102 twice per week on a 2-days-on, 5-days-off schedule.

Enrolled patients also receive an MRI scan at week 16 and every 12 weeks thereafter. The primary end point of part A is safety, and tumor volume reduction is a secondary end point.

In part B of the trial, patients will be randomly assigned to receive 1.2 mg of AL102 per day or placebo.

Regarding safety reported for evaluable patients at all 3 doses in part A (n = 42), most adverse effects (AEs) were grade 1 or 2, grade 3 AEs were uncommon, and no grade 4/5 AEs were reported.² Four serious AEs were observed in 3 patients, though they were deemed unrelated to AL102. AEs leading to treatment discontinuation included diarrhea, stomatitis, elevated alanine aminotransferase, and rash.

References

1. Ayala Pharmaceuticals announces fast track designation granted by US FDA for AL102 in progressing desmoid tumors. News release. Ayala Pharmaceuticals. September 27, 2022. Accessed September 27, 2022. https://bit.ly/3LKp9LI
2. Gounder MM, Jones RL, Chugh R, et al. Initial results of phase II/III trial of AL102 for treatment of desmoid tumors (DT). Ann Oncol. 2022;33(suppl 7):S681-S700. doi:10.1016/annonc/annonc1073
3. Ayala Pharmaceuticals presents positive interim data from RINGSIDE pivotal phase 2/3 trial of AL102 in desmoid tumors at ESMO Congress 2022. News release. Ayala Pharmaceuticals. September 12, 2022. Accessed September 27, 2022. https://bit.ly/3UKl79Y