Taletrectinib for Non-Small Cell Lung Cancer

(TRUST-II Trial)

Not currently recruiting at 112 trial locations

Overseen By Lian Li

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Nuvation Bio Inc.

Must not be taking: CYP3A4/5 inhibitors, QT prolonging

Disqualifiers: Other malignancy, Lung disease, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of taletrectinib, a new treatment for advanced non-small cell lung cancer (NSCLC). All participants will receive taletrectinib to evaluate its effectiveness against this cancer type. The trial seeks individuals with NSCLC that tests positive for a specific gene change called ROS1 fusion, which a doctor can confirm. Suitable participants may have previously tried other treatments or might be new to treatment options. Those with advanced lung cancer and this gene change may find this trial suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically those that are potent inhibitors or inducers of CYP3A4/5 or P-glycoprotein, and those that can prolong the QT interval, at least 14 days before starting the study treatment and while on treatment.

Is there any evidence suggesting that taletrectinib is likely to be safe for humans?

Research has shown that taletrectinib is generally well-tolerated by patients with non-small cell lung cancer (NSCLC). Studies have found that taletrectinib is effective for many, with a high response rate. Most patients can handle the treatment without major issues.

One study found that taletrectinib has a good safety record, with low rates of serious side effects. While some side effects might occur, they are usually not severe. Other trials for similar conditions have also tested the drug, supporting its safety.

Overall, the research provides promising information about the safety of taletrectinib for people with NSCLC. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Taletrectinib is unique because it specifically targets alterations in the ROS1 and NTRK genes, which are known to drive the growth of certain non-small cell lung cancers. Most current treatments for this type of cancer, like chemotherapy or other targeted therapies, don't specifically address these genetic changes. Researchers are excited about taletrectinib because it has the potential to be more effective for patients whose tumors have these specific genetic profiles, possibly leading to better outcomes and fewer side effects than broader treatments.

What evidence suggests that taletrectinib might be an effective treatment for non-small cell lung cancer?

Research shows that taletrectinib has strong potential for treating non-small cell lung cancer (NSCLC) with ROS1 fusion. Studies have found that many patients experienced tumor shrinkage, resulting in a high overall response rate (ORR). Specifically, taletrectinib controlled the disease in 88.3% of cases, even among patients previously treated with crizotinib. This indicates that taletrectinib can remain effective after other treatments. Additionally, taletrectinib is generally well-tolerated, with fewer severe side effects, making it a promising option for advanced NSCLC. ^{1 2 3 6 7}

Who Is on the Research Team?

Wei Wang, MD, PhD

Principal Investigator

Nuvation Bio Inc.

Are You a Good Fit for This Trial?

Adults with advanced non-small cell lung cancer (NSCLC) that tests positive for ROS1 fusion can join this trial. They should have at least one measurable tumor, be able to follow the study plan and COVID-19 rules, and not be pregnant or breastfeeding. People who've had certain recent treatments or have serious health issues like heart disease, untreated brain metastases, active infections, or a history of significant lung problems are excluded.

Inclusion Criteria

Life expectancy ≥12 weeks

My cancer is confirmed to be advanced or has spread, through testing.

Compliance with study scheduled visits, treatment plans, and procedures

Exclusion Criteria

Presence of severe medical or mental diseases in which risk is increased by study participation

I haven't taken certain medications in the last 14 days.

I am taking medication that can affect my heart's rhythm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive taletrectinib monotherapy in 21-day cycles, with some receiving combination therapy with carboplatin and pemetrexed for 4 cycles

Until disease progression

Regular visits for tumor response evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment, including long-term survival follow-up

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Taletrectinib

Trial Overview The trial is testing Taletrectinib's safety and effectiveness as a solo treatment for NSCLC. It includes patients who may or may not have used similar drugs before. The focus is on those whose cancer has spread beyond the original site and involves assessing how well they respond to this medication.

How Is the Trial Designed?

Group I: Taletrectinib Experimental Treatment 1 Intervention

Single-arm trial whereby all consented, enrolled, eligible patients receive taletrectinib

Taletrectinib is already approved in China for the following indications:

Approved in China as DOVBLERON for:

• ROS1-positive non-small cell lung cancer (NSCLC)

Who Is Running the Clinical Trial?

Nuvation Bio Inc.

Lead Sponsor

Trials

12

Recruited

1,200+

AnHeart Therapeutics Inc.

Industry Sponsor

Trials

13

Recruited

1,900+

Published Research Related to This Trial

The combination of sitravatinib and tislelizumab was generally well-tolerated in patients with locally advanced/metastatic non-small cell lung cancer (NSCLC), with treatment-related adverse events occurring in 98.4% of patients, but no new safety concerns were identified.

Objective response rates varied by cohort, with the highest response (57.1%) in patients with PD-L1-positive non-squamous histology who had not received prior systemic therapy, indicating potential efficacy in treatment-naïve populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAFFRON-103: a phase 1b study of the safety and efficacy of sitravatinib combined with tislelizumab in patients with locally advanced or metastatic non-small cell lung cancer. Zhao, J., Yu, X., Huang, D., et al.[2023]

In a phase 2 study with a minimum of 5-year follow-up, the combination of dabrafenib and trametinib showed a high overall response rate of 68.4% in pretreated patients and 63.9% in treatment-naive patients with BRAF V600E-mutant metastatic NSCLC, indicating strong efficacy.

The therapy demonstrated a manageable safety profile, with pyrexia being the most common side effect (56%), and provided substantial overall survival benefits, with median overall survival of 18.2 months for pretreated patients and 17.3 months for treatment-naive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis. Planchard, D., Besse, B., Groen, HJM., et al.[2022]

In a review of 10 studies involving 18 patients with BRAF non-V600E mutant lung cancer, targeted therapies like trametinib showed a potential clinical benefit rate of 34%, indicating some efficacy in this patient group.

There is currently no standard treatment for BRAF non-V600E mutations, as responses to therapies like vermurafenib and dabrafenib vary significantly, highlighting the need for more extensive research to establish effective treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Strategic Exploration of Targeted Therapy for BRAF Non-V600E Mutant Lung Cancer]. Zhang, H., Gao, J., Guo, W., et al.[2022]

In a retrospective study of 35 patients with advanced BRAF-mutant lung adenocarcinoma treated with BRAF inhibitors, the overall response rate was 53%, and the disease control rate was 85%, indicating significant efficacy of these targeted therapies.

Patients with the V600E mutation had a median overall survival of 25.3 months with first-line therapy, compared to 11.8 months for those with other BRAF mutations, highlighting the importance of mutation type in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the European EURAF Cohort. Gautschi, O., Milia, J., Cabarrou, B., et al.[2022]

In a study using a lung adenocarcinoma patient-derived xenograft model, the BRAFG469V mutation was identified as the only oncogenic mutation, and the model showed sensitivity to multiple EGFR tyrosine kinase inhibitors (TKIs).

The research suggests that clinically approved EGFR TKIs, such as gefitinib and osimertinib, can be repurposed to effectively target and treat non-small cell lung cancer patients with the BRAFG469V mutation, expanding treatment options for this specific genetic alteration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung Cancer Driven by BRAFG469V Mutation Is Targetable by EGFR Kinase Inhibitors. Huo, KG., Notsuda, H., Fang, Z., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.9066

Taletrectinib (AB-106; DS-6051b) in metastatic non-small ... Taletrectinib demonstrated promising clinical activity with high ORR and good tolerability in ROS1 fusion positive NSCLC patients.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8474193/

Efficacy of Taletrectinib (AB-106/DS-6051b) in ROS1+ NSCLC The confirmed ORR for crizotinib pretreated patients (N = 6) was 33.3% (95% CI: 9.7–70.0) with a disease control rate of 88.3% (95% CI: 443.6–97.0). The median ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06564324

NCT06564324 | A Phase III Study Comparing Taletrectinib ... A Phase III Study Comparing Taletrectinib With Standard Therapy in ROS1 Positive Locally Advanced or Metastatic Non-small Cell Lung Cancer Patients.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40179330/

Taletrectinib in ROS1+ Non-Small Cell Lung Cancer: TRUST Taletrectinib showed a high response rate with durable responses, robust IC activity, prolonged PFS, favorable safety, and low rates of neurologic adverse ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT503076

Comparable efficacy and safety of taletrectinib for ... Comparable efficacy and safety of taletrectinib for advanced ROS1+ non–small cell lung cancer across pivotal studies and between races and world regions.

6. investors.nuvationbio.com investors.nuvationbio.com/news/news-details/2025/Nuvation-Bio-Enrolls-First-Patient-in-TRUST-IV-Phase-3-Study-of-IBTROZI-taletrectinib-for-the-Adjuvant-Treatment-of-ROS1-Positive-Early-Stage-Non-Small-Cell-Lung-Cancer/default.aspx

Nuvation Bio Enrolls First Patient in TRUST-IV Phase 3 ... “Based on the proven efficacy and safety data supporting IBTROZI's use and approval in advanced ROS1-positive non-small cell lung cancer, we are ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2823%2903243-X/fulltext

1373P Efficacy and safety of taletrectinib in patients (Pts) ... 1373P Efficacy and safety of taletrectinib in patients (Pts) with ROS1+ non-small cell lung cancer (NSCLC): Interim analysis of global TRUST-II study.