The first participant has been dosed in the Phase 2 clinical trial TENACITY, which is evaluating Ayala Pharmaceuticals‘ investigational therapy AL101 as a treatment for Notch-activated recurrent or metastatic triple negative breast cancer (TNBC).

AL101 is an investigational small molecule that inhibits Notch proteins. This family of cellular proteins plays important roles in governing cell growth during development. In some cancers, however, abnormal Notch signaling helps to facilitate cancer growth and survival.

“We believe the need for a novel therapeutic option is critical as Notch-activated TNBC correlates with a poorer prognosis and higher rates of potential relapse,” Roni Mamluk, PhD, CEO of Ayala, said in a press release.

In its first phase, TENACITY (NCT04461600) intends to enroll up to 26 people with TNBC whose tumors have abnormal Notch signaling, as assessed by biopsy of the tumor. Of note, TNBC refers to breast cancer that is not driven by hormone receptors (i.e., estrogen and progesterone receptors) or by abnormal HER2 levels. The study is specifically enrolling individuals whose cancer has recurred or progressed after three or fewer lines of prior therapy.

An additional 41 participants with Notch-activated, recurrent or metastatic TNBC are sought to be enrolled in the second phase of the study, which is sponsored by Alaya. Recruitment for TENACITY is ongoing at several locations in the U.S. and Israel; additional information is available here.

All of the participants in the open-label trial will be treated with AL101. The trial’s main goal is to determine the overall response rate — that is, the number of individuals whose tumors get smaller after treatment. Duration of response, quality of life measurements, and survival-related endpoints (goals) also will be measured.

Results from TENACITY are expected by the end of this year, according to Ayala.

Alaya also is evaluating AL101 as a potential treatment for adenoid cystic carcinoma (ACC) — a rare type of cancer that affects secretory glands, like the salivary glands — in an ongoing Phase 2 clinical trial called ACCURACY (NCT03691207). The U.S. Food and Drug Administration has granted AL101 both fast track and orphan drug designations for the treatment of ACC.

“The dosing of the first patient in our Phase 2 TENACITY trial is an important step for Ayala as we now have two ongoing Phase 2 clinical trials for AL101 monotherapy in heavily pre-treated patient populations, further building its safety and efficacy profile across these difficult to treat, Notch-activated cancers,” Mamluk said.

“We are confident that TNBC is a logical second indication for AL101 based on extensive preclinical work and we look forward to further advancing the TENACITY trial,” she added.