FDA Grants Taletrectinib Priority Review for Advanced ROS1+ NSCLC

Taletrectinib demonstrated favorable efficacy and tolerability data in the TRUST-I and TRUST-II trials for the treatment of patients with advanced non–small cell lung cancer.

The FDA has granted priority review to a new drug application for taletrectinib, an investigational next-generation ROS1 TKI, for the treatment of patients with advanced ROS1-positive non–small cell lung cancer (NSCLC), according to a news release from the drug’s developer, Nuvation Bio.¹

A Prescription Drug User Fee Act date has been set for June 23, 2025.

Taletrectinib previously received the breakthrough therapy designation, and is the only ROS1 TKI in development to have done so, for the treatment of patients with locally advanced or metastatic NSCLC.² In July 2024, taletrectinib also received orphan drug designation for ROS1-positive NSCLC.³

Pooled data from the single-arm, phase 2, Chinese TRUST-I trial (NCT04395677) evaluating the safety, pharmacokinetics, and efficacy of taletrectinib monotherapy in advanced NSCLC, and the global, single-arm, phase 2 TRUST-II trial (NCT04919811) evaluating the safety and efficacy of taletrectinib monotherapy in advanced NSCLC are the basis for the application.

“We are thrilled to reach this important milestone for taletrectinib, a significant step forward for people living with ROS1-positive NSCLC who urgently need new treatment options,” David Hung, MD, founder, president, and chief executive officer of Nuvation Bio, stated in the press release.¹ “With data from over 300 patients—the largest ROS1-positive NSCLC dataset to date supporting an NDA—taletrectinib has demonstrated the potential to deliver durable and meaningful benefits.”

The pooled results from both trials were presented at the 2024 European Society of Medical Oncology (ESMO) Congress .⁴

In both trials, patients received 600 mg of taletrectinib once daily.

Key inclusion criteria include an age of 18 years or older, locally advanced or metastatic NSCLC, an ECOG performance status of 0 or 1, evidence of ROS1 fusion, and at least 1 measurable lesion per RECIST v1.1 criteria.

Of TKI-naive patients, 20% had received prior chemotherapy and 23% had brain metastases. Of TKI-pretreated patients, 37% had received prior chemotherapy and 49% had brain metastases. Additionally, 94% (n = 256) of patients had stage IV disease.

Primary study end points were independent review committee (IRC)-assessed cORR. Secondary end points include intracranial cORR, DOR, PFS, and Safety.

Combined, the presented dataset included 337 patients with advanced ROS1-positive NSCLC; 160 of whom were not previously treated with a ROS1 TKI and 113 of whom were previously treated with crizotinib (Xalkori) or entrectinib (Rozlytrek).

In the TKI-naive population, the confirmed objective response rate (cORR) was 88.8% (95% CI, 82.8%-93.2%), 86.5% (95% CI, 71.2%-95.5%) in TKI-naive patients with brain metastases, and 87.5% (95% CI, 71.01%-96.49%) in TKI-naive patients who underwent prior chemotherapy. The intracranial cORR was 76.5% (95% CI, 50.1%-93.2%).

Also, in TKI-naïve patients, at a median follow-up of 21.2 months (range, 3.6-46.6), the median progression-free survival (PFS) and median duration of response were 45.6 months (95% CI, 29.0–not reached [NR]) and 44.2 months (95% CI, 30.4–NR), respectively.

In the TKI-pretreated population, the cORR was 55.8% (95% CI, 46.1%-65.1%), was 56.4% (95% CI, 42.3%-69.7%) in TKI-pretreated patients with brain metastases, and 59.5% (95% CI, 43.3%-74.4%) in TKI-pretreated patients who underwent prior chemotherapy. For TKI-pretreated patients with G2032R mutations, cORR was 61.5% (95% CI, 31.6%-86.1%). The intracranial cORR was 65.6% (95% CI, 46.8%-81.4%)

Also, in the TKI-pretreated population, at a median follow-up of 21.0 months (range, 3.9-45.4), the median PFS and median DOR were 9.7 months (95% CI, 7.4-12.0) and 16.6 months (95% CI, 10.6-27.3), respectively.

The most common treatment-emergent adverse effects (TEAEs) of any grade were increased aspartate aminotransferase (72.1%), increased alanine aminotransferase (68.0%), diarrhea (63.2%), and nausea (47.2%). Of grade 3 or higher, the most common TEAEs were increased alanine aminotransferase (10.1%), increased aspartate aminotransferase (7.7%), decreased neutrophil count (4.2%), and anemia (3.6%).

TEAEs leading to dose reductions occurred in 28.8% of patients, 12.5% of which were due to abnormal liver function tests, and treatment discontinuations due to TEAEs occurred in 6.5% of patients.

References

1. 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. News release. Nuvation Bio. December 23, 2024. Accessed December 23, 2024. https://tinyurl.com/bfty8jfw
2. AnHeart Therapeutics receives FDA breakthrough therapy designation for taletrectinib in ROS1-positive non-small cell lung cancer. News release. AnHeart Therapeutics. August 3, 2022. Accessed December 23, 2024. https://bwnews.pr/3oZrw2o
3. Search orphan drug designations and approvals. U.S. Food and Drug Administration. Accessed December 23, 2024. https://tinyurl.com/3ev3p36j
4. Perol M, Li W, Pennell NA, et al. Pooled efficacy and safety from 2 pivotal phase 2 trials of taletrectinib in patients with advanced or metastatic ROS1+ non–small cell lung cancer. Presented at: 2024 European Society of Medical Oncology Congress; September 13-17, 2024; Barcelona, Spain. Abstract 1289P.