On January 4, 2021 Ayala Pharmaceuticals, Inc. (NASDAQ: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, reported the completion of its end-of-Phase 1 meeting with the U.S. Food and Drug Administration (FDA) on AL102, a potent, selective, oral gamma secretase inhibitor (GSI), for the treatment of desmoid tumors (Press release, Ayala Pharmaceuticals, JAN 4, 2021, View Source [SID1234573635]). The FDA has agreed, based on data from AL101 and AL102 studies including durable responses observed in patients with Desmoid tumors, to proceed with a Phase 2/3 pivotal study, which can potentially be used as a registrational study. Ayala expects to initiate the pivotal Phase 2/3 RINGSIDE study in adult and adolescent patients with desmoid tumors in the first half of 2021.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"This exciting news of entering into a potentially registration-enabling pivotal trial, earlier than expected, represents an important step for Ayala as we are able to accelerate the development of AL102 for the treatment of desmoid tumors based on positive and encouraging feedback from the FDA following our end-of-Phase 1 meeting," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "Desmoid tumors are a rare, debilitating and often disfiguring class of soft-tissue tumors for which there are currently no approved therapies. We believe AL102 is well positioned to potentially provide effective systemic treatment based on the body of data conducted by BMS in patients with desmoid tumors implicating the role of Notch pathway in activating aberrant growth pathways contributing to desmoid tumor growth."
The pivotal Phase 2/3 RINGSIDE trial is designed to evaluate the efficacy, safety and tolerability of AL102 in adult and adolescent patients with desmoid tumors. Part 1 of the study will be open label and will enroll up to 36 patients with progressive desmoid tumors in three study arms across three doses of AL102: 1.2 mg daily (QD), 2 mg twice weekly (QIW), and 4mg twice weekly (QIW) with initial follow up of safety, tolerability and tumor volume by MRI after 16 weeks in order to determine the optimal dose. At the end of part 1, all patients will be eligible to enroll into an open label extension study at the selected dose where long-term efficacy and safety will be monitored.
Part 2 of the study will start immediately after dose selection from part 1 and will be a double-blind placebo-controlled study enrolling up to 156 patients with progressive disease, randomized 2:1 between AL102 or placebo. The study’s primary endpoint will be progression free survival (PFS) with secondary endpoints including, objective response rate (ORR), duration of response (DOR) and patient reported Quality of Life (QOL) measures.
The study is expected to commence in the first half of 2021 with an initial interim data read-out from part 1 and dose selection expected by mid-2022 with part 2 of the study to commence immediately thereafter.
About AL102
AL102 is a potent, selective, oral gamma secretase inhibitor (GSI). AL102 is currently being developed for the treatment of desmoid tumors, as well as in combination with Novartis’ B-cell maturation antigen (BCMA)-targeting agents for the treatment of multiple myeloma (MM).
About Desmoid Tumors
Desmoid tumors, also called aggressive fibromatosis or desmoid-type fibromatosis, are rare connective tissue tumors that typically arise in the upper and lower extremities, abdominal wall, head and neck area, mesenteric root and chest wall with the potential to arise in additional parts of the body. Desmoid tumors do not metastasize, but often aggressively infiltrate neurovascular structures and vital organs. People living with desmoid tumors are often limited in their daily life due to chronic pain, functional deficits, general decrease in their quality of life and organ dysfunction. Desmoid tumors have an annual incidence of approximately 1,700 patients in the United States and typically occur in patients between the ages of 15 and 60 years. They are most commonly diagnosed in young adults between 30-40 years of age and are more prevalent in females. Today, surgery is no longer regarded as the cornerstone treatment of desmoid tumors due to high rate of recurrence post-surgery and there are currently no FDA-approved systemic therapies for the treatment of unresectable, recurrent or progressive desmoid tumors.