Taletrectinib Shows Consistent Efficacy Across ROS1+ NSCLC Subgroups Regardless of Prior Chemotherapy or Fusion Partner
核心洞察
Nuvation Bio presented new subgroup analyses from the pivotal TRUST-I and TRUST-II studies at the IASLC 2026 World Conference on Lung Cancer in Seoul.
In TKI-naive patients, objective response rates were 90.0% with prior chemotherapy versus 89.8% without, with median durations of response of 48.3 and 54.3 months.
Efficacy was also consistent by ROS1 (搜索) fusion partner, with ORRs of 89.5% for CD74 fusions and 88.9% for non-CD74 fusions in TKI-naive patients.
Nuvation Bio Inc. (NYSE: NUVB) reported new subgroup analyses from the pivotal TRUST-I and TRUST-II studies showing that IBTROZI (搜索) (taletrectinib) delivered consistent efficacy in both TKI-naive and TKI-pretreated patients with advanced ROS1 (搜索)-positive (ROS1+) non-small cell lung cancer (NSCLC), regardless of prior chemotherapy exposure or ROS1 fusion partner. The data were presented at the IASLC 2026 World Conference on Lung Cancer (WCLC) in Seoul, Republic of Korea.
The analyses address a practical clinical question: whether patients who begin chemotherapy before a ROS1 (搜索) fusion is identified can still benefit from targeted therapy once testing confirms the driver alteration.
Consistent Response Regardless of Prior Chemotherapy
Among TKI-naive patients, the confirmed objective response rate (ORR) was 90.0% in those with prior chemotherapy (n=30) and 89.8% in those with no prior chemotherapy (n=127). Median duration of response (DOR) was 48.3 months and 54.3 months, respectively.
The company noted that while the analysis shows patients can respond to IBTROZI (搜索) following prior chemotherapy, treatment guidelines continue to recommend waiting to begin treatment until biomarker results come back and initiating targeted therapy as soon as a ROS1 (搜索) fusion is confirmed. These findings reinforce the importance of early biomarker testing and prompt transition to targeted therapy.
"The most important step for a patient with newly diagnosed non-small cell lung cancer is to conduct comprehensive biomarker testing to identify a targetable driver and start the right targeted therapy as early as possible," said Jorge Nieva, M.D., medical oncologist at USC Norris Comprehensive Cancer Center. "Guidelines recommend holding treatment until biomarker testing comes back, which can create pressure to begin chemotherapy first. These analyses offer reassurance that patients who do start chemotherapy before a ROS1 (搜索) fusion is identified can still respond well once they transition to taletrectinib. We hope this gives clinicians added confidence to move promptly to targeted therapy as soon as biomarker testing confirms a ROS1 fusion."
Fusion Partner Does Not Appear to Affect Benefit
Both TKI-naive and TKI-pretreated patients consistently benefited from IBTROZI (搜索) regardless of ROS1 (搜索) fusion partner. A fusion partner is the gene that merges with ROS1, resulting in a hybrid, cancer-driving protein that fuels tumor growth. The most common partner is CD74, which accounts for up to half of all ROS1 fusions in NSCLC.
Among TKI-naive patients, ORR was 89.5% in those with CD74 fusions (n=19) and 88.9% in those with non-CD74 fusions (n=18). Median DOR was comparable between the two groups at 44.8 and 43.3 months, respectively, as was median progression-free survival (PFS) at 46.1 and 44.6 months.
"We've already been impressed by the durable efficacy of IBTROZI (搜索), with many responses lasting over four years, and now these new data answer critical questions about its consistency," said David Hung, M.D., Founder, President and Chief Executive Officer of Nuvation Bio. "These analyses show that patients derive a similar, powerful benefit from IBTROZI across multiple subgroups, which we hope gives clinicians even greater confidence in selecting IBTROZI for any patient with advanced ROS1 (搜索)+ NSCLC."
Previously at AACR 2026, the pooled analysis of all TKI-naive patients in the TRUST-I and TRUST-II studies showed a confirmed ORR of 89.8% and a median DOR of 49.7 months.
Long-Term Safety Profile Unchanged
With long-term follow-up, IBTROZI (搜索) continued to demonstrate a manageable safety profile consistent with previous reports, with no new safety signals identified. The most common adverse events in the overall TRUST-I and TRUST-II pooled safety analyses were increased AST and ALT, diarrhea, nausea and vomiting, which were mostly low grade.
The prescribing information lists hepatotoxicity as a warning, with 88% of patients experiencing increased AST (including 10% Grade 3/4) and 85% experiencing increased ALT (including 13% Grade 3/4); fatal liver events occurred in 0.6% of patients. Interstitial lung disease/pneumonitis occurred in 2.3% of patients, including 1.1% Grade 3/4. QTcF increases of >60 msec from baseline and QTcF >500 msec occurred in 13% and 2.6% of patients, respectively. Among adverse reactions reported in at least 20% of patients were diarrhea (64%), nausea (47%), vomiting (43%), dizziness (22%), rash (22%), constipation (21%) and fatigue (20%).
Trial Program and Regulatory Status
IBTROZI (搜索) is an oral, potent, CNS-active, selective, next-generation ROS1 (搜索)-inhibitor therapy. On June 11, 2025, following Priority Review and Breakthrough Therapy designations for both TKI-naive and TKI-pretreated disease, the U.S. Food and Drug Administration approved taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1+ NSCLC.
The TRUST clinical program comprises three registrational studies. TRUST-I (NCT04395677) and TRUST-II (NCT04919811) are Phase 2 single-arm studies evaluating IBTROZI (搜索) in adults with advanced ROS1 (搜索)+ NSCLC in China (N=173) and globally (N=189), respectively; the primary endpoint of both is confirmed objective response rate as assessed by an independent review committee. TRUST-IV (NCT07154706) is a Phase 3 placebo-controlled study evaluating IBTROZI for the adjuvant treatment of adults with resected early-stage ROS1+ NSCLC, enrolling approximately 180 patients in the U.S., Canada, Europe, Japan and China, with disease-free survival by investigator as the primary endpoint and an estimated primary completion date in 2030. Nuvation Bio is also sponsoring TRUST-III (NCT06564324), a confirmatory randomized Phase 3 study evaluating IBTROZI versus crizotinib in 194 patients in China with advanced ROS1+ NSCLC who have not previously received ROS1 TKIs.
Disease Burden
Each year, more than one million people globally are diagnosed with NSCLC, the most common form of lung cancer. Approximately 2% of patients with NSCLC are estimated to have ROS1 (搜索)+ disease. About 35% of patients newly diagnosed with metastatic ROS1+ NSCLC have tumors that have spread to the brain, and the brain is the most common site of disease progression, with about 50% of previously treated patients developing central nervous system metastases.