On December 14, 2023 Aadi Bioscience, Inc. (NASDAQ: AADI), a biopharmaceutical company focused on developing and commercializing precision therapies for genetically defined cancers with alterations in mTOR pathway genes, reported results from a planned interim analysis on the first third of participants in the ongoing tumor-agnostic PRECISION1 trial evaluating nab-sirolimus in patients with TSC1 or TSC2 inactivating alterations (Press release, Aadi Bioscience, DEC 14, 2023, View Source [SID1234638581]).
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"Our tumor agnostic PRECISION1 trial is designed to elucidate the impact of nab-sirolimus on cancers expressing inactivating alterations of TSC1 or TSC2, regardless of tumor type. We are encouraged by the preliminary data from this pre-planned analysis and by the responses and clinical benefit demonstrated in advanced cancer patients who have failed an average of three prior lines of therapy," said Loretta Itri, MD, CMO of Aadi Bioscience. "Full enrollment in the trial is expected by the spring of 2024 and we believe we are on track to generate compelling clinical evidence for advancing nab-sirolimus toward potential expansion of the current registration, bringing this innovative therapeutic agent to more cancer patients."
The interim analysis includes data from the first third of trial participants (n=40) with a minimum of 4.5 months of follow-up, including investigator-assessed response and safety analyzed separately in each of the TSC1 and TSC2 arms. Nine different tumor types were enrolled in the TSC1 arm and 13 tumor types were enrolled in the TSC2 arm.
Efficacy of nab-sirolimus in patients with tumors harboring pathogenic inactivating alteration in TSC1
Of the 22 patients enrolled, 19 patients received ≥ 1 post baseline scan and were evaluable for efficacy. Observations included:
A 26% Overall Response Rate (ORR) including 5 partial responses (PR) with 4 confirmed responses and 1 unconfirmed response (uPR)
All responses were ongoing at the time of data cutoff. The patient with uPR remains on treatment and is awaiting a confirmatory scan
9 patients had stable disease (SD), 3 of which were greater than or equal to six months in duration, resulting in a clinical benefit rate of 42% (5 PR + 3 SD ≥ 6 mos)
Patients were heavily pre-treated with median of 3 prior lines of therapy
Median time to response was 1.4 months
Responses were seen across four different epithelial carcinomas
60% of responders experienced > 50% tumor reduction
Efficacy of nab-sirolimus in patients with tumors harboring pathogenic inactivating alteration in TSC2
Of the 18 patients enrolled, all 18 patients received ≥ 1 post baseline scan and were evaluable for efficacy. Observations included:
An 11% ORR including 2 PRs with 1 confirmed and 1 uPR
12 patients had SD, 3 of which were greater than or equal to six months resulting in a clinical benefit rate of 28% (2 PR + 3 SD ≥ 6 mos)
Patients were heavily pre-treated with median of 3.5 prior lines of therapy; 50% had ≥ 5 prior lines of therapy
Responses were seen in one epithelial carcinoma and one sarcoma
No new safety signals were observed, and no grade four treatment-related events or deaths occurred. One patient discontinued the study due to grade two pneumonitis that completely resolved after discontinuation of therapy. Across both arms, the safety profile was consistent with the nab-sirolimus label and the mTOR inhibitor drug class.
80 patients are currently enrolled in the PRECISION1 trial, supporting the two-thirds interim analysis expected in the third quarter of 2024. The ORR analysis in this cohort will be based on independent radiological review with a minimum of six months of follow-up for all patients. The trial is expected to be completed by the end of 2024 with results anticipated in early 2025.
Conference Call Information
The Aadi management team is hosting a conference call and webcast today at 5:00 pm ET (2:00 pm PT) to discuss the interim results from the PRECISION1 trial.
Participants may access a live webcast of the call and the associated slide presentation on these data through the "Investors & News" page of the Aadi Bioscience website at aadibio.com. To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company’s website for at least 30 days.
About PRECISION1
The PRECISION1 trial is a multi-center, open-label, tumor-agnostic prospective registration intended clinical trial of nab-sirolimus. This tumor agnostic study will evaluate approximately 60 mTOR inhibitor naïve patients in each of two independent study arms, or approximately 120 in total, comprised of patients with solid tumors harboring pathogenic inactivating alterations in either TSC1 or TSC2 genes. In September 2021, the FDA designated the investigation of nab-sirolimus for the treatment of adults and adolescents with solid tumors that have a pathogenic inactivating alteration of the TSC1 or TSC2 gene as a Fast Track development program.
Nab-Sirolimus 100 mg/m2 is 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.