“With additional follow-up time, these updated findings from the TRUST studies show notable progression-free survival results and demonstrate that responses with IBTROZI remain durable, with a well-characterized, manageable safety profile,” said Geoffrey Liu, M.D., Princess Margaret Cancer Centre, Temerty School of Medicine, University of Toronto. “The results further support the recent approval of IBTROZI in the U.S., which has added an important new option for a range of patients with this form of lung cancer, regardless of prior exposure to tyrosine kinase inhibitor therapy.”
“Disease progression remains one of the greatest threats to people with advanced ROS1+ non-small cell lung cancer, especially those being treated in the first-line setting,” said David Hung, M.D., Founder, President and Chief Executive Officer of Nuvation Bio. “These long-term data emphasize impressive PFS and durability of response, with a tolerable and manageable safety profile that helps patients stay on therapy so they can continue to benefit. We remain excited about the promise of IBTROZI and look forward to further data generation from continued follow up in the TRUST studies.”
For patients in TRUST-II who had not previously been treated with a ROS1 tyrosine kinase inhibitor (TKI-naïve; n=54), confirmed objective response rate (cORR) was 85.2% at a median follow-up of 20.5 months. Median progression-free survival (PFS) was not yet reached, meaning more than half of patients had not progressed, and the longest PFS was observed at 31.6 months and ongoing. Median duration of response (DOR) was also not yet reached; the longest DOR was observed at 30.4 months and ongoing. A DOR of at least 12 months was achieved by 74.0% of patients and of at least 18 months by 68% of patients based on Kaplan-Meier estimates. An intracranial response was achieved by 66.7% (6/9) of patients with brain metastases.
In TKI-pretreated patients (n=47), cORR was 61.7% at a median follow-up of 20.4 months. Median PFS was 11.8 months, and median DOR was 19.4 months. An intracranial response was achieved by 56.3% (9/16) of patients with brain metastases.
Updated TRUST-I Study Results
For TKI-naïve patients in TRUST-I (n=103), cORR was 90.3% at a median follow-up of 40.9 months. Median PFS was 44.6 months. Median DOR was not yet reached; the longest DOR was observed at 46.9 months and ongoing. An intracranial response was achieved by 87.5% (7/8) of patients with brain metastases.
In TKI-pretreated patients (n=66), cORR was 51.5% at a median follow-up of 35.1 months. Median PFS was 7.6 months, and median DOR was 13.2 months. An intracranial response was achieved by 75.0% (12/16) of patients with brain metastases.
Pooled Safety Data from TRUST-I and TRUST-II
Safety characterization in the integrated analysis from across trials (N=337) included in the poster presentation demonstrated a favorable safety and tolerability profile for IBTROZI with manageable adverse events (AEs). AEs of clinical interest (diarrhea, nausea, vomiting and dizziness) were transient and resolved quickly (median resolution range 1-3 days). No treatment discontinuations occurred due to these AEs of clinical interest. AST and ALT elevations occurred in 76% of patients and led to one patient discontinuing treatment.
About ROS1+ NSCLC:
Each year, more than one million people globally are diagnosed with non-small cell lung cancer (NSCLC), the most common form of lung cancer. It is estimated that approximately 2% of patients with NSCLC have ROS1+ disease. About 35% of patients newly diagnosed with metastatic ROS1+ NSCLC have tumors that have spread to their brain. The brain is also the most common site of disease progression, with about 50% of previously treated patients developing central nervous system (CNS) metastases.
About IBTROZI:
IBTROZI is an oral, potent, CNS-active, selective, next-generation ROS1 inhibitor therapy. On June 11, following Priority Review and Breakthrough Therapy Designations for both first- and second-line or later, the U.S. Food and Drug Administration (FDA) approved IBTROZI for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC. Learn more at IBTROZI.com.
About the TRUST Clinical Program:
The TRUST clinical program evaluating IBTROZI for the treatment of adult patients with advanced ROS1+ NSCLC included two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, which enrolled 173 patients, and TRUST-II (NCT04919811), a global study, which enrolled 189 patients. The primary endpoint of these registrational studies is confirmed objective response rate (cORR) as assessed by an independent review committee (IRC). Secondary endpoints include intracranial cORR, duration of response, progression-free survival, and safety.
About Nuvation Bio:
Nuvation Bio is a global oncology company focused on tackling some of the toughest challenges in cancer treatment with the goal of developing therapies that create a profound, positive impact on patients’ lives. Our diverse pipeline includes taletrectinib (IBTROZI™), a next-generation ROS1 inhibitor; safusidenib, a brain-penetrant IDH1 inhibitor; NUV-1511, an innovative drug-drug conjugate (DDC) designed for targeted cancer treatment; and NUV-868, a BD2-selective BET inhibitor.
Nuvation Bio was founded in 2018 by biopharma industry veteran David Hung, M.D., who previously founded Medivation, Inc., which brought to patients one of the world’s leading prostate cancer medicines. Nuvation Bio has offices in New York, San Francisco, Boston, and Shanghai.
For more information, please visit www.nuvationbio.com
