Ibtrozi (taletrectinib) / Daiichi Sankyo, Innovent Biologics, NewG Lab Pharma, Nippon Kayaku, Nuvation Bio - LARVOL DELTA

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the NCCN Drugs & Biologics Compendium (NCCN Compendium) for Non-Small Cell Lung Cancer, Version 5.2025. (NCCN)

NCCN guideline • Non Small Cell Lung Cancer

Onco360 Has Been Selected as a National Specialty Pharmacy Partner for IBTROZI (taletrectinib), Manufactured by Nuvation Bio Inc. (The Manila Times) - "Onco360, the nation's leading independent Specialty Pharmacy, has been selected as a pharmacy partner by Nuvation Bio Inc. for IBTROZI (taletrectinib), a kinase inhibitor approved for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC)."

Commercial • Non Small Cell Lung Cancer

FDA approves taletrectinib for ROS1-positive non-small cell lung cancer (FDA) - "On June 11, 2025, the Food and Drug Administration approved taletrectinib (Ibtrozi, Nuvation Bio Inc.), a kinase inhibitor, for adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). Efficacy was evaluated in patients with locally advanced or metastatic, ROS1-positive NSCLC enrolled in two multicenter, single-arm, open-label clinical trials, TRUST-I (NCT04395677) and TRUST-II (NCT04919811)."

Evidence highlight • FDA approval • Non Small Cell Lung Cancer • ROS1

Novel Targeted Treatment for NSCLC Effective Across Multiple Regions and Populations (Cleveland Clinic) - "Pooled analysis of TRUST-I and TRUST-II revealed that taletrectinib elicited a confirmed overall response rate (cORR) of 85.2% in TKI- naive patients and 57.1% in TKI-pretreated patients. In a comparison of response rates between TRUST-I and TRUST-II, cORRs were consistent for TKI-naive (91% vs. 85%; RR: 0.94 [95% CI: 0.83, 1.07]) and TKI-pretreated patients (52% vs. 62%; RR: 1.20 [95% CI: 0.87, 1.66]). In a pooled analysis stratified by race, Asian and non-Asian patients had similar cORRs in both TKI-naive (89% vs. 84%; RR: 0.94 [95% CI: 0.77, 1.15]) and TKI-pretreated (52% vs. 68%; RR: 1.30 [95% CI: 0.93, 1.82]) groups. Within the TRUST-II study, cORRs were high in TKI-naive patients regardless of region (Western: 81%; Asia: 88%), prior chemotherapy (yes: 90%; no: 84%) and race (Caucasian: 83%, Asian: 86%, other races: 86%)."

Retrospective data • Non Small Cell Lung Cancer

Comparable efficacy and safety of taletrectinib for advanced ROS1+ non–small cell lung cancer across pivotal studies and between races and world regions. (ASCO 2025) - P2 | "Taletrectinib showed comparable efficacy and safety that were not impacted by geographic and racial factors. Therefore, the clinical benefit of taletrectinib is broadly applicable to ROS1+ NSCLC patients globally."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Real-world Study of Taletrectinib for Advanced ROS1+ NSCLC With Brain Metastases (clinicaltrials.gov) - P=N/A | N=100 | Not yet recruiting | Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

New trial • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Taletrectinib promotes pyroptosis in colorectal carcinoma via SRC/AKT/mTOR axis inhibition. (PubMed, Sci Rep) - "Moreover, the effect of taletrectinib in promoting pyroptosis was reversed by treatment with the SRC agonist, tolimidone, both in vitro and in vivo. Overall, our findings suggest that taletrectinib suppresses tumor growth by inducing GSDME-mediated pyroptosis via the SRC/AKT/mTOR signaling pathway, indicating that taletrectinib shows potential as a promising therapeutic agent against CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ANXA5 • CASP3 • GSDME • NTRK

Nuvation Bio To Present New Data from Pivotal Clinical Studies of Taletrectinib in Advanced ROS1-Positive Non-Small Cell Lung Cancer at ASCO 2025 Annual Meeting (Businesswire) - "Nuvation Bio...announced that additional results from TRUST-I and TRUST-II, its pivotal Phase 2 clinical studies on the efficacy and safety of taletrectinib for the treatment of advanced ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC), will be presented at the upcoming American Society of Clinical Oncology (ASCO) 2025 Annual Meeting..."

P2 data • Non Small Cell Lung Cancer

Taletrectinib vs Entrectinib in ROS1-Positive (ROS1+) Non-Small Cell Lung Cancer (NSCLC): A Matching-Adjusted Indirect Comparison (MAIC) (ISPOR 2025) - P1, P2 | "Taletrectinib showed significantly improved outcomes vs entrectinib in TKI-naive patients with ROS1+ NSCLC in the cross-trial MAIC analysis, including higher ORR and substantially reduced rate of progression. Additional analyses with more mature DOR and PFS data, along with a comparative analysis of safety outcomes, will provide a comprehensive benefit-risk assessment."

CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Nuvation Bio to Present Matching-adjusted Indirect Comparison Data for Taletrectinib vs. Entrectinib at ISPOR 2025 (Businesswire) - "Nuvation Bio...announced that new data from a matching-adjusted indirect comparison study evaluating taletrectinib versus entrectinib in ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC) will be presented in a poster session at ISPOR 2025, the Professional Society for Health Economics and Outcomes Research’s annual conference, taking place May 13-16, 2025 in Montreal, QC, Canada."

Clinical data • Non Small Cell Lung Cancer

Nuvation Bio Reports First Quarter 2025 Financial Results and Provides Business Update (Businesswire) - "Recent Pipeline Updates: (i) Taletrectinib, ROS1 inhibitor: Advanced ROS1+ NSCLC: The Priority Review of the Company’s NDA for taletrectinib for advanced ROS1+ NSCLC (line agnostic, full approval) is progressing on time with all planned inspections now completed. The PDUFA goal date of June 23, 2025, positions Nuvation Bio to commercialize taletrectinib in the U.S., if approved, in mid-2025...; (ii) Safusidenib, mIDH1 inhibitor: Diffuse IDH1-mutant glioma: The Company expects to provide an update on the pivotal study design for the safusidenib program in the second half of 2025; (iii) NUV-1511, drug-drug conjugate (DDC): Advanced solid tumors: The Company expects to provide an update from the Phase 1/2 dose escalation study of NUV-1511 in the second half of 2025."

Clinical protocol • Launch • P1/2 data • PDUFA • Glioma • Non Small Cell Lung Cancer

Zidesamtinib Selective Targeting of Diverse ROS1 Drug-Resistant Mutations. (PubMed, Mol Cancer Ther) - "At clinically relevant concentrations, zidesamtinib robustly inhibited >1,500 pooled ROS1 mutants with virtually no resistance emerging (≤1%), outperforming comparators crizotinib, entrectinib, and repotrectinib. Zidesamtinib also induced more durable responses than repotrectinib and taletrectinib in an aggressive intracranial ROS1 G2032R xenograft model. A 2.2 Å co-crystal structure with ROS1 G2032R, the most frequently identified ROS1 resistance mutation, reveals that zidesamtinib uniquely accommodates the mutated residue while potentially clashing with TRK, consistent with its selective ROS1-targeting design and supported by computational modeling. Taken together, these data support zidesamtinib's potential as a novel best-in-class ROS1 inhibitor."

Journal • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

New drugs approved by the NMPA in 2024: Synthesis and clinical applications. (PubMed, Eur J Med Chem) - "This group included 9 chemical drugs and 9 biological products, with notable breakthrough therapies such as taletrectinib, lutetium monoclonal antibodies, and donanemab receiving special recognition. The 2024 data reflect China's growing capabilities in drug innovation and its commitment to addressing critical medical needs through accelerated regulatory pathways."

Journal • Gastrointestinal Disorder • Oncology

Taletrectinib, a next generation selective ROS1 inhibitor, inhibits growth of ROS1 wild-type and ROS1-G2032R xenografts (AACR 2025) - P2 | "While several inhibitors for ROS1 have been FDA approved, including crizotinib, entrectinib and, more recently, repotrectinib, each present unique challenges. Taletrectinib is being evaluated in patients with locally advanced or metastatic ROS1-positive NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global study. Based on the integrated analysis of the TRUST-I and TRUST-II clinical studies, an NDA has been submitted for taletrectinib to the U.S. FDA for the treatment of patients with locally advanced or metastatic ROS1-positive NSCLC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD74 • NTRK2 • SLC34A2

Taletrectinib in ROS1 mutated Non–Small Cell Lung Cancer (2 Minute Medicine) - "This study is a pooled analysis of two prospective studies of Taletrectinib in the ROS1+ NSCLC population....For TKI-naïve patients (n=160) compared to TKI-pretreated patients (n = 113), the ORR was 88.8% (8 CR and 134 PR) with DCR 95.0% for TKI-naïve patients compared to ORR 55.8% (5 CR and 58 PR), with DCR 87.6% for TKI-pretreated patients. Median DoR in patients with ORR was 44.2 months, with an estimated 36-month DoR rate being 57.7% for TKI-naïve patients compared to a median DoR of 16.6 months with a 12-month DoR of 61.1% for TKI-pretreated patients. Median TtR was 1.4 months in both populations. Median PFS was 45.6 months with an estimated 36-month PFS rate being 52.6% in TKI-naïve patients, compared to a median PFS was 9.7 months with a 12-month PFS rate being 39.7% for TKI-pretreated patients. Median OS was NA in both populations, with an estimated 36-month OS rate being 66.3% for TKI-naïve patients..."

Retrospective data • Non Small Cell Lung Cancer

Nuvation Bio to Present Matching-adjusted Indirect Comparison Data for Taletrectinib vs. Crizotinib During Mini Oral Presentation at the European Lung Cancer Congress 2025 (Businesswire) - "Nuvation Bio Inc....announced that new data from a matching-adjusted indirect comparison study evaluating taletrectinib versus crizotinib in ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC) will be reported in a mini oral presentation at the European Lung Cancer Congress taking place March 26–29, 2025 in Paris, France."

P3 data • Non Small Cell Lung Cancer

Nuvation Bio to Present New Nonclinical Data for Taletrectinib at the American Association for Cancer Research Annual Meeting 2025 (Businesswire) - "Nuvation Bio...announced that new nonclinical data for taletrectinib in ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC) will be presented at the American Association for Cancer Research (AACR) Annual Meeting....Presentation Overview: Title: Taletrectinib, a next generation selective ROS1 inhibitor, inhibits growth of ROS1 wild-type and ROS1-G2032R xenografts....Abstract Number: 5612."

Preclinical • Non Small Cell Lung Cancer

Efficacy and safety of taletrectinib for treatment of ROS1 positive non-small cell lung cancer: a systematic review. (PubMed, Expert Opin Pharmacother) - "Crizotinib and entrectinib are the preferred first line therapy for treating ROS1 fusion-positive NSCLC (ROS1+NSCLC). Taletrectinib shows significant efficacy and favorable safety profile for ROS1-positive NSCLC, particularly in treatment-naïve or TKI-resistant patients. Further large-scale trials are warranted to confirm its long-term safety and efficacy."

Journal • Review • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • NTRK2 • ROS1

Targeting ROS1 rearrangements in non-small cell lung cancer: Current insights and future directions. (PubMed, Cancer) - "First-generation inhibitors, such as crizotinib and entrectinib, have demonstrated impressive efficacy, with objective response rates exceeding 60%-70%...Next-generation TKIs, including lorlatinib, taletrectinib, and repotrectinib, have been developed to overcome these challenges...Zidesamtinib, a highly selective next-generation ROS1 inhibitor, further addresses TRK-mediated off-target neurological toxicities seen with prior agents, and is poised to offer improved tolerability...In addition, the development of novel diagnostic tools, including RNA-based next-generation sequencing, has enhanced the detection of functional ROS1 fusions by ensuring that patients with actionable mutations receive appropriate targeted therapies. These advances highlight the evolving landscape of treatment for ROS1-positive NSCLC, with the aim of maximizing long-term survival and quality of life."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Taletrectinib in ROS1+ Non-Small Cell Lung Cancer: TRUST. (PubMed, J Clin Oncol) - "Taletrectinib showed a high response rate with durable responses, robust IC activity, prolonged PFS, favorable safety, and low rates of neurologic adverse events in TKI-naïve and pretreated patients."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Taletrectinib vs crizotinib in ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC): A matching-adjusted indirect comparison (MAIC) (ELCC 2025) - P2 | "The incidence of grade 3 TRAEs was comparable between taletrectinib and crizotinib (45% [95% CI: 31.2%, 59.8%] vs 36% [95% CI: 23.1%, 50.2%], respectively). Conclusions In this cross-trial MAIC analysis, taletrectinib showed significantly improved outcomes compared with crizotinib in TKI-naive patients with ROS1+ NSCLC, including higher ORR, a significant reduction in the risk of disease progression and mortality, and with comparable grade 3 TRAEs"

Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • ROS1

Six new product launches in 2025 with growth momentum anticipated (PRNewswire) - "Three additional approved precision therapies to strengthen lung and hematological cancer franchises: Dovbleron; Limertinib; Jaypirca"

Commercial • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma

Efficacy of subsequent therapy following the progression of crizotinib in advanced ROS1+ NSCLC in real word setting (ELCC 2025) - "Next-generation ROS1-TKI (repotrectinib, taletrectinib, TL-139) demonstrated superior efficacy over non-next-generation TKI (PFS: 13.9 m vs 4.4 m, HR = 0.46, 95%CI: 0.24–0.86, p = 0.04; ORR: 70% vs 20%, p = 0.002). ORR was 66.7% for patients carrying G2032R mutation treated with next-generation TKI while non-next-generation TKI presented dismal response in another 7 patients with secondary ROS1 mutation (G2032R, D2033N, L2026M, S1986F), only 1 patient with L2026M mutation showed response to lorlatinib, the rest of them demonstrated progressive disease... Next-generation ROS1-TKI should be the preferred subsequent choice after the resistance of crizotinib especially for patients with ROS1 secondary mutation. Lolatinib should also be considered particularly in patients with CNS metastases while entrectinib should no be routinely recommended. IO-based combination treatment was no better than traditional platinum-doublet chemo plus anti-VEGF therapy."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

TRUST-III: A Phase III Study Comparing Taletrectinib With Standard Therapy in ROS1 Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients (clinicaltrials.gov) - P3 | N=138 | Recruiting | Sponsor: Nuvation Bio Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Nippon Kayaku announces completion of marketing authorization application of a novel ROS1 inhibitor, taletrectinib, for use in patients with advanced ROS1-positive Non-Small Cell Lung Cancer in Japan (Nippon Kayaku Press Release) - "Nippon Kayaku Co., Ltd...announces that it has completed submission of a marketing authorization application for taletrectinib (development code: AB-106/DS-6051b) to the Pharmaceuticals and Medical Devices Agency...This application is based on the results of a global Phase II clinical study (TRUST-II) in patients with advanced ROS1-positive non-small cell lung cancer (NSCLC), which were presented at the World Conference on Lung Cancer (WCLC 2024) held in September 2024."

Japan filing • Non Small Cell Lung Cancer