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 

The multicenter, open-label phase 2 study is enrolling patients with pathogenic inactivating 

 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 

 mutations, and arm B will feature patients with 

mutations. 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 

Although the trial is stratifying patients by 

 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 

 alterations was associated with responses. Response were not as higher in patients with 

mutations; however, since such a small number of patients with 

 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 

 mutations on a larger scale, Schulte concludes.

Videos

Brian Schulte, MD, discusses the ongoing phase 2 PRECISION 1 basket trial evaluating the use of nab-sirolimus for adult and adolescent patients with malignant solid tumors harboring TSC1/2 mutations.

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 prevalence of 

 mutations are pathogenic mutations that are seen in a variety of histologic subtypes and malignancies, but the prevalence of the mutation varies depending on the type of cancers, Schulte explains. For example, the mutation is as frequent as 8% in types of bladder cancer vs 3% in types of sarcomas, Schulte adds. Altogether, the 

 mutations can be seen in thousands of patients across the country, Schulte says.

 mutations are tumor suppressors by their nature, with the purpose of abrogating proteins that are downstream, such as mTOR, Schulte continues. The thought is that these mechanisms will lead to further tumor growth through an alternate pathway, Shulte adds. Whether those specific mutations alone can impact prognosis is not known, although previous studies revealed that inhibition of the mTOR pathway leads to high response rates and durable responses in patients, Schulte concludes.

Brian Schulte, MD, discusses the prevalence of TSC1/TSC2 mutations in cancer.


Brian Schulte, MD

Articles

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

Dr. Schulte on the Prevalence of TSC1/TSC2 Mutations in Cancer