Event Details

Abstracts and poster presentation details are below:

Title: "Phase 2, multicenter, open-label basket trial of nab-sirolimus for patients with inactivating alterations in TSC1 or TSC2 (PRECISION I)"
Date and Time: Monday, April 17, 2023, 9:00 AM - 12:30 PM
Session Title: Phase II and Phase III Clinical Trials in Progress 
Presentation Number: CT057

Abstract highlights:

• nab-Sirolimus is a novel albumin-bound mTOR inhibitor (mTORi) approved in the US for adult patients with advanced malignant PEComa.
• Eligible patients are ≥12 years old and mTORi-naïve, possess malignant solid tumors with TSC1 or TSC2 inactivating alterations (confirmed by central review of sequencing reports), and have received appropriate standard treatments, as determined by the investigator.
• Available data from the AMPECT exploratory analysis and an expanded access program suggest acceptable efficacy and safety of nab-sirolimus, an mTORi with enhanced antitumor activity, in patients with solid tumors harboring inactivating alterations in TSC1 and/or TSC2.
• nab-Sirolimus 100 mg/m2 will be given weekly intravenously over 30 minutes on Days 1 and 8 of each 21-day cycle. The primary endpoint is overall response rate per independent radiographic review (IRR) using RECIST v1.1. Other endpoints include duration of response, time to response, progression-free survival by IRR, overall survival, patient-reported quality of life, and safety.
• Enrollment began in March 2022. Collaboration with leading next-generation sequencing vendors will expedite the identification of patients with qualifying TSC1 or TSC2 mutations; study access will be facilitated through a "just-in-time" approach to trial location activation.
• Based on the prevalence of TSC1 or TSC2 inactivating alterations, the most frequent tumor types expected are bladder, hepatobiliary, endometrial, soft tissue sarcoma, ovarian, and esophagogastric.

Title: "Synergistic anti-tumor activity of nab-sirolimus in combination with KRAS inhibitors (KRASis) sotorasib and adagrasib in KRAS G12C NSCLC and bladder cancer xenografts"
Date and Time: Tuesday, April 18, 2023, 1:30 - 5:00 PM
Session Category: Clinical Research Excluding Trials
Session Title: Combination Therapies for Cancer
Presentation Number: 5484

Abstract highlights:

• KRAS is frequently mutated in non-small cell lung cancer (NSCLC) and other tumor types, with KRAS G12C mutation representing ~12% of patients with NSCLC. Sotorasib and adagrasib are approved for the treatment of KRAS­ G12C NSCLC. Mutations in KRAS may lead to mTORC1 activation, and mTOR may contribute to adaptive resistance to KRASis.
• This study investigated the antitumor activity of nab-sirolimus in combination with KRASis in KRAS G12C NSCLC and bladder xenograft models.
• nab-sirolimus in combination with either sotorasib or adagrasib showed greater tumor growth inhibition, a higher meaningful tumor regression rate and synergistic antitumor activity vs single agent therapy.
• A multicenter, single-arm, open-label Phase 1/2 clinical study is planned to determine the recommended Phase 2 dose, safety, tolerability, and efficacy for the combination of adagrasib and nab-sirolimus in patients with KRAS G12C tumors.

Title: "Biomarker analysis from AMPECT correlating response to nab-sirolimus with TSC1 and TSC2 inactivating alterations"
Date and Time: Wednesday, April 19, 2023, 9:00 AM - 12:30 PM
Session Category: Clinical Research Excluding Trials
Session Title: Late-Breaking Research: Clinical Research 3
Presentation Number: LB288

Abstract Highlights:

• An exploratory biomarker analysis was performed on samples from patients enrolled in the AMPECT study, a Phase 2, multicenter, open-label trial in advanced malignant PEComa (NCT02494570).
• A variety of pathogenic inactivating alterations were observed in TSC1 and TSC2 genes, though TSC2 mutations were most commonly frameshift mutations; no recurring mutations were observed.
• A tumor-agnostic study (PRECISION 1: NCT05103358) is now recruiting patients with pathogenic inactivating TSC1 or TSC2 alterations to further examine these biomarker findings.