Dr. Schulte on the PRECISION 1 Trial of Nab-Sirolimus in TSC1/2-Mutated Solid Tumors

Brian Schulte, MD, sarcoma medical oncologist, the University of California San Francisco (UCSF) Health, discusses the ongoing phase 2 PRECISION 1 basket trial (NCT05103358) evaluating the use of nab-sirolimus (ABI-009) for adult and adolescent patients with malignant solid tumors harboring TSC1/2 mutations.

The multicenter, open-label phase 2 study is enrolling patients with pathogenic inactivating TSC1 or TSC2 mutations that are confirmed by central evaluation of next-generation sequencing. Patients are required to have received all standard therapies appropriate for their tumor type and stage of disease, or be unlikely to tolerate or derive benefit from standard-of-care therapy. Prior treatment with an mTOR inhibitor, including nab-sirolimus, is not permitted.

The trial features 2 arms: arm A will include patients with TSC1 mutations, and arm B will feature patients with TSC2mutations. The primary end point of PRECISION 1 is overall response rate (ORR), and secondary end points include duration of response, disease control rate, time to response, progression-free survival, overall survival, and safety. Regarding ORR, investigators hope to observe improved responses compared with historical outcomes in this setting for patients with tumors harboring TSC1/2 mutations, Schulte adds.

Although the trial is stratifying patients by TSC1 and TSC2 mutations, it is difficult to predict whether investigators will observe a significant difference in outcomes or toxicities between the two arms, Schulte explains. Previously published data from the phase 2 AMPECT trial (NCT02494570), which led to the FDA approval of nab-sirolimus for adult patients with unresectable or metastatic, malignant perivascular epithelioid cell tumor, also showed that the presence of TSC2 alterations was associated with responses. Response were not as higher in patients with TSC1mutations; however, since such a small number of patients with TSC1 or TSC2 mutations were included in this exploratory analysis of AMPECT, it was difficult to draw firm conclusion about outcomes for patients with either mutation, Schulte adds.

Given the results of the exploratory analysis of AMPECT, PRECISION 1 will aim to investigate to potential benefit of nab-sirolimus in patients with TSC1 or TSC2 mutations on a larger scale, Schulte concludes.