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

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

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 | "Clinical Trial Registration Number: NCT04395677, NCT04919811 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

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

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

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

Nuvation Bio Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (Businesswire) - "Recent Pipeline Updates: Taletrectinib, ROS1 inhibitor: Advanced ROS1+ NSCLC:...In March 2025, Nippon Kayaku completed submission of a MAA for taletrectinib for advanced ROS1+ NSCLC to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). As part of an exclusive license agreement, Nippon Kayaku will commercialize taletrectinib in Japan."

Commercial • Non Small Cell Lung Cancer

Nuvation Bio Secures Up to $250 Million in Non-Dilutive Financings from Sagard Healthcare Partners (Businesswire) - "Nuvation Bio...announced non-dilutive financings of up to $250 million with Sagard Healthcare Partners (Sagard). The transaction comprises a royalty interest financing of $150 million and a senior term loan of up to $100 million...The transaction also provides Nuvation Bio with a path to potential profitability without the need to raise additional capital...Subject to the approval of taletrectinib by the U.S. Food and Drug Administration (FDA) on or prior to September 30, 2025, Sagard will provide Nuvation Bio with an upfront cash payment of $150 million. In return, Sagard will receive tiered royalties on U.S. net sales of taletrectinib, including 5.5% of annual U.S. net sales up to $600 million and 3.0% of annual U.S. net sales between $600 million and $1 billion. Nuvation Bio will retain all annual U.S. net sales above $1 billion....In addition to the royalty financing, Sagard has committed to a 5-year, senior secured term loan of up to $100 million..."

Financing • Non Small Cell Lung Cancer

Tale EAP: Expanded Access Program of Taletrectinib in Patients with Advanced or Metastatic ROS1-Positive NSCLC (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Nuvation Bio Inc.

New trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thoracic Cancer

Pooled efficacy and safety from 2 pivotal phase II trials of taletrectinib in patients with advanced ROS1+ NSCLC (JSMO 2025) - No abstract available

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ROS1

Taletrectinib: “Taletrectinib has the highest overall response rate and median progression free survival of any ROS1 inhibitor in the first line (TKI-naïve) setting”; Non-small cell lung cancer (43rd Annual J.P. Morgan Healthcare Conference, Nuvation Bio) - “Taletrectinib has the highest overall response rate and median progressionfree survival of any ROS1 inhibitor in the second line (TKI-pretreated) setting”

Clinical data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Taletrectinib: “Taletrectinib has the highest overall response rate and median progression free survival of any ROS1 inhibitor in the first line (TKI-naïve) setting”; Non-small cell lung cancer (43rd Annual J.P. Morgan Healthcare Conference, Nuvation Bio) - “Taletrectinib has the highest overall response rate and median progressionfree survival of any ROS1 inhibitor in the second line (TKI-pretreated) setting”

Clinical data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Nuvation Bio Announces Expanded Access Program in the U.S. for Taletrectinib in Advanced ROS1-positive Non-Small Cell Lung Cancer (Businesswire) - "Nuvation Bio Inc...today announced it has initiated an Expanded Access Program (EAP) for taletrectinib in the U.S. for the treatment of patients with locally advanced or metastatic ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC) when no comparable or satisfactory alternative therapy options are available....The EAP, as authorized by the U.S. Food and Drug Administration (FDA), allows patients with serious or immediately life-threatening ROS1+ NSCLC to access taletrectinib outside of the ongoing pivotal Phase 2 TRUST-II study."

Commercial • Non Small Cell Lung Cancer • ROS1

Innovent Announces Second New Drug Application of DOVBLERON (Taletrectinib Adipate Capsule, ROS1 Inhibitor) was Approved by China’s National Medical Products Administration (PRNewswire) - "Innovent Biologics, Inc...announced that China's National Medical Products Administration (NMPA) has approved the second New Drug Application (NDA) of DOVBLERON (taletrectinib adipate capsule), a next-generation ROS1 tyrosine kinase inhibitor (TKI), for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC. The approval is based on positive results from the pivotal Phase 2 TRUST-I trial (NCT04395677), a multicenter, open-label, single-arm trial that evaluated the safety, tolerability and efficiency of taletrectinib in Chinese patients with advanced ROS1-positive NSCLC....'We recently just launched the first batch of DOVBLERON to market, rapidly bringing this precision therapy to NSCLC patients who need novel treatment options'."

China approval • Evidence highlight • Launch non-US • Non Small Cell Lung Cancer • ROS1

Taletrectinib vs repotrectinib in ROS1-positive (ROS1+) non–small cell lung cancer (NSCLC): A matching-adjusted indirect comparison (MAIC) (ESMO Asia 2024) - P1/2, P2 | "Further analyses with more mature DOR and PFS data are needed to confirm our findings Table: 637P MAIC: Outcomes comparison in TKI-naive and TKI-pretreated cohorts Outcomes TKI naive TKI pretreated Taletrectinib after matching (N=152) Repotrectinib (N=71) Taletrectinib after matching (N=104) Repotrectinib (N=56) ORR, % 95% CI 88.8% 82.7%–93.3% 78.9% 67.6%–87.7% 55.8% 45.7%–65.5% 37.5% 24.9%–51.5% DOR, hazard ratio 95% CI 0.76 0.404–1.438 0.86 0.419–1.776 PFS, hazard ratio 95% CI 0.93 0.656–1.311 0.97 0.578–1.612 DOR, duration of response; MAIC, matching adjusted indirect comparison; ORR, objective response rate; PFS, progression-free survival; TKI, tyrosine kinase inhibitor. ."

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

Innovent Receives Approval of DOVBLERON (Taletrectinib Adipate Capsule, ROS1 Inhibitor) by China's National Medical Products Administration (PRNewswire) - "Innovent Biologics, Inc...today announced that China's National Medical Products Administration (NMPA) has approved a New Drug Application (NDA) of DOVBLERON (taletrectinib adipate capsule), a next-generation ROS1 tyrosine kinase inhibitor (TKI), for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who have been previously treated with ROS1 TKIs....The approval is based on positive results from the pivotal Phase 2 TRUST-I trial (NCT04395677)..."

China approval • Non Small Cell Lung Cancer

U.S. Food and Drug Administration Accepts for Priority Review Nuvation Bio’s New Drug Application for Taletrectinib for the Treatment of Advanced ROS1-positive Non-Small Cell Lung Cancer (Businesswire) - "Nuvation Bio Inc...today announced that the U.S. FDA has accepted the company’s NDA for taletrectinib, an investigational next-generation ROS1 tyrosine kinase inhibitor (TKI), for the treatment of advanced ROS1+ NSCLC (line agnostic). The U.S. FDA has granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 23, 2025. Priority Review designation underscores the significant advancement taletrectinib may offer patients with ROS1+ NSCLC, for which there remains a high unmet need for new treatment options...'As we prepare for a launch as early as mid-2025, we’re taking critical steps to establish Nuvation Bio as a commercial oncology organization'....The NDA is based on the pooled results from the pivotal Phase 2 TRUST-I and TRUST-II studies of taletrectinib..."

FDA filing • Launch US • PDUFA • Priority review • Non Small Cell Lung Cancer