Dr Bazhenova on Taletrectinib Label Update and Subgroup Data in ROS1+ NSCLC

The FDA has approved a supplemental new drug application (sNDA) updating the label for taletrectinib (Ibtrozi), a next-generation, CNS-active, selective ROS1 tyrosine kinase inhibitor (TKI), to reflect a median duration of response (DOR) of 49.7 months in TKI-naive patients in the phase 2 TRUST-I trial (NCT04395677).¹ The indication is unchanged from the June 2025 approval for adults with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC), which was based on TRUST-I and the phase 2 TRUST-II trial (NCT04919811).^1,2

In a pooled analysis of TRUST-I and TRUST-II presented at the 2026 American Association for Cancer Research (AACR) Annual Meeting, taletrectinib produced a confirmed overall response rate (ORR) of 89.8%, an intracranial ORR of 76.5% (n = 17), a median DOR of 49.7 months, and a median progression-free survival (PFS) of 46.1 months among 157 TKI-naive patients.³ Additional subgroup analyses from the 2026 IASLC World Conference on Lung Cancer (WCLC) showed ORRs of 90.0% (n = 30) vs 89.8% (n = 127) in patients with and without prior chemotherapy, and 89.5% (n = 19) vs 88.9% (n = 18) in TKI-naive patients with CD74 vs non-CD74 fusion partners.^4,5

In an interview with Targeted Oncology^TM, Lyudmila Bazhenova, MD, professor of medicine at the University of California San Diego Moores Cancer Center, discussed the approval, the new WCLC analyses, and the ongoing adjuvant TRUST-IV trial.

Targeted Oncology: What was the analysis that led to this approval?

Lyudmila Bazhenova, MD: The analysis was presented at AACR in early 2026, and it shows the efficacy of taletrectinib in TKI-naive and TKI-pretreated patient populations with longer follow-up.

Does anything from these data or this approval change how you are considering treating patients?

It doesn't change my practice, because I am a believer in taletrectinib. I still think this gives us the best reported PFS with a very long follow-up, and this approval is just based on the data that were presented already. There is nothing truly new with this approval. We did present new data at WCLC, which clarify some of the questions in ROS1-positive non–small cell lung cancer where you are considering taletrectinib.

Can you go into those new data?

At AACR, we presented an updated analysis of efficacy in TKI-naive patients, which is where I primarily use taletrectinib. The ORR in the pooled analysis was 89.8%. There was a very high intracranial ORR of 76.5%. The median DOR in the pooled population was 49.7 months, and the median PFS was 46.1 months. This is very durable efficacy. There were no surprises in safety, no new safety information was released, and the side effects were very similar to what was previously presented.

At WCLC, we presented additional subset analyses. One mainly looked at the efficacy of taletrectinib in patients who had received prior chemotherapy. In stage 4 lung cancer, we usually like to wait for next-generation sequencing before giving targeted therapy, but if the patient is very sick or there is a significant delay in the sequencing results, sometimes we have to give chemotherapy. The efficacy in patients who received prior chemotherapy and those who didn't was very similar, with a confirmed response rate of 90% and 89.8% [respectively], and very similar median PFS and median DOR.

While I still think that we need to wait for molecular testing before starting first-line therapy for patients with stage IV non–small cell lung cancer, this gives you reassurance that if you have to give chemotherapy, you can. If you started chemotherapy and then the results came back with a ROS1 fusion, I would recommend switching to a ROS1 TKI rather than continuing chemotherapy, mainly for the quality-of-life benefits.

The second analysis presented, which I think is also important, looked at the efficacy of taletrectinib by ROS1 fusion partner. We know that in ROS1-rearranged lung cancer, the majority of fusions are CD74, but there are also non-CD74 fusions. The data presented at WCLC showed that there is no difference in the efficacy of taletrectinib regardless of the fusion partner.

For your colleagues, are there any considerations clinicians should be aware of with taletrectinib?

Not really. It's a drug that is tolerated relatively well. The main side effect is transaminitis, and the majority of it is low grade, so I usually recommend monitoring LFTs [liver function tests] when you start taletrectinib. Otherwise, diarrhea is there, and the majority of the diarrhea episodes are also grade 1. So it's about being proactive and managing the diarrhea caused by taletrectinib. Otherwise, in my personal experience, this is a medication that is very easily tolerated by patients.

What is the next step in this line of research?

For stage IV disease, I don't think there are any additional trials that would be important for me. But there is a very important trial ongoing in the adjuvant setting. There is a clinical trial [the phase 3 TRUST-IV study; NCT07154706] looking at adjuvant taletrectinib for patients who have early-stage lung cancer, receive surgery, and are then found to have a ROS1 [rearrangement].⁶ I think this is a very important trial, and I hope that when the study finishes, it will be positive. Then we can add ROS1-rearranged patients in line with our EGFR- and ALK-rearranged patients, where we are using adjuvant targeted therapy.

REFERENCES

1. Nuvation Bio announces FDA approval of supplemental new drug application for IBTROZI (taletrectinib) with updated duration of response in TKI-naïve advanced ROS1-positive non–small cell lung cancer. News release. Nuvation Bio Inc. September 17, 2026. Accessed October 6, 2026. https://tinyurl.com/rhu9w4dw

2. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. FDA. June 11, 2025. Accessed October 6, 2026. https://tinyurl.com/mr2ypz2p

3. Bazhenova L, et al. Taletrectinib in tyrosine kinase inhibitor (TKI)-naïve patients with ROS1+ non-small cell lung cancer (NSCLC): updated data from TRUST-I and TRUST-II. Cancer Res. 2026;86(suppl 8):CT300. Presented at: American Association for Cancer Research Annual Meeting; April 17-22, 2026; San Diego, CA.

4. Taletrectinib across key subgroups in patients with ROS1+ non-small cell lung cancer: results from TRUST-I and TRUST-II. Poster presented at: IASLC 2026 World Conference on Lung Cancer; September 12-15, 2026; Seoul, Republic of Korea.

5. Nuvation Bio announces new analyses reinforcing the durable, consistent efficacy of IBTROZI (taletrectinib) across key patient subgroups in advanced ROS1+ NSCLC at 2026 World Conference on Lung Cancer. News release. Nuvation Bio Inc. September 15, 2026. Accessed October 6, 2026. https://tinyurl.com/k39jkt8z

6. Phase 3 study of taletrectinib vs placebo as an adjuvant therapy in ROS1 positive NSCLC (TRUST-IV). ClinicalTrials.gov. Accessed October 6, 2026. https://clinicaltrials.gov/study/NCT07154706