China’s NMPA Accepts MAA for Foritinib in ALK+ Advanced NSCLC

China’s National Medical Products Administration (NMPA) has accepted a marketing authorization application (MAA) seeking the approval of foritinib (SAF-189) for the treatment of patients with ALK-positive, locally advanced or metastatic non–small cell lung cancer (NSCLC).1

The MAA is supported by data from the phase 3 REMARK trial (NCT06569420). Findings from the study presented at the 2024 IASLC World Conference on Lung Cancer showed that patients treated with foritinib (n = 139) achieved a median progression-free survival (PFS) that was not reached (NR) compared with 13.93 months (95% CI, 11.07-19.35) for patients treated with crizotinib (Xalkori; n = 136; HR, 0.23; 95% CI, 0.14-0.38; P < .0001).

Foritinib is a highly potent, ALK/ROS1 inhibitor capable of penetrating the central nervous system (CNS). Along with the REMARK trial, phase 2 trials have been completed in China investigating the agent in patients with ROS1-positive advanced NSCLC.

REMARK Overview

The multicenter, open-label, randomized REMARK study enrolled patients at least 18 years of age with histologically or cytologically confirmed stage IIIB/C or IV NSCLC that was ALK-positive per the Ventana immunohistochemistry assay.2 Prior systemic therapy for locally advanced or metastatic disease was not permitted. Key inclusion criteria consisted of measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 to 2, a life expectancy of at least 12 weeks, and adequate organ and bone marrow function.

Patients were excluded if they had CNS metastases requiring clinical local intervention; requiring systemic treatment with corticosteroids and at least 10 mg per day prednisone or an equivalent; or requiring sustained treatment with an antiepileptic drug. Other exclusion criteria consisted of spinal cord metastasis with potential risk of symptomatic spinal cord compression; a history of acute pancreatitis within 1 year of enrollment; a history of interstitial lung disease; and uncontrollable pleural effusion, ascites, and pericardial effusion.

Investigators randomly assigned patients 1:1 to receive foritinib at 160 mg once per day or crizotinib at 250 mg twice per day.1

PFS per independent review committee assessment served as the trial’s primary end point. Secondary end points included investigator-assessed PFS; overall response rate (ORR); time to response (TTR); duration of response (DOR); intracranial ORR (IC-ORR), IC-TTR, IC-DOR, and time to CNS progression; overall survival (OS); and safety.

Additional Efficacy and Safety Outcomes

Further data from the study demonstrated that patients in the foritinib arm experienced an ORR of 92.8% (95% CI, 87.17%-96.50%) compared with 80.9% (95% CI, 73.26%-87.12%) for those given crizotinib (odds ratio, 3.04; 95% CI, 1.41-6.57). All responses in both arms were partial responses (PR). In the foritinib arm, the rates of stable disease and progressive disease were 4.3% and 1.4%, respectively; these respective rates were 16.2% and 0.7% in the control arm. Notably, 1.4% of patients in the foritinib arm and 2.2% of patients in the crizotinib arm were not evaluable for response. The median DOR was NR in the experimental arm vs 15.93 months (95% CI, 11.17-NR) in the control arm.

The IC-ORR was 100% (95% CI, 69.15%-100%) in the foritinib arm (n = 10) compared with 50.0% (95% CI, 26.02%-73.98%) in the crizotinib arm (n = 18). The IC–complete response (IC-CR) and IC-PR rates in the experimental arm were 20.0% and 80.0%, respectively. In the control arm, the IC-CR, IC-PR, IC-SD, and IC-PD rates were 11.1%, 38.9%, 44.4%, and 5.6%, respectively. The median IC-DOR was NR in the foritinib arm vs 11.01 months (95% CI, 2.86-NR) in the crizotinib arm.

At a median follow-up of 17.12 months for the foritinib arm (n = 138) and 16.43 months for the crizotinib arm (n = 135), safety data showed that any-grade treatment-related adverse effects (TRAEs) occurred in 97.8% and 98.5% of patients, respectively. The respective rates of grade 3 or higher TRAEs were 37.7% and 55.6%. Serious TRAEs occurred in 15.9% of patients treated with foritinib vs 11.9% of patients given crizotinib. No treatment-related deaths were reported in either arm.

In the experimental arm, TRAEs led to dose interruption, dose reduction, and treatment discontinuation in 26.8%, 23.9%, and 3.6% of patients, respectively. These respective rates were 35.6%, 37.8%, and 2.2% in the control arm.

References

1. Fosun Pharma's independently developed innovative lung cancer drug foritinib (SAF-189) marketing authorization application has been accepted by NMPA. News release. Fosun Pharma. March 10, 2025. Accessed March 10, 2025. https://www.fosunpharma.com/en/content/details37_16133.html
2. Study of comparing SAF-189s with crizotinib In first line ALK-positive advanced and metastatic NSCLC. ClinicalTrials.gov. Updated August 26, 2024. Accessed March 10, 2025. https://clinicaltrials.gov/study/NCT06569420