NCCN Inclusion 15 Days Post-FDA Approval Strengthens U.S. Prescription Base
37% Response Rate in Non-Cholangiocarcinoma Patients; Targeting "The Next Keytruda" via Tumor-Agnostic Clinical Trials
HLB’s (028300) new cholangiocarcinoma drug, Rivfloza (generic name: lirafugratinib), has been included in the National Comprehensive Cancer Network (NCCN) clinical practice guidelines following its recent U.S. Food and Drug Administration (FDA) approval. Its inclusion in this essential reference for U.S. oncologists significantly bolsters the drug's prescription base in the local market.
HLB is also conducting clinical trials to expand the drug's indications beyond cholangiocarcinoma to other solid tumors. By validating its therapeutic effects in various cancers, including pancreatic cancer, that carry FGFR2 gene abnormalities, the company is positioning Rivfloza as a "tumor-agnostic" treatment.
NCCN Inclusion 15 Days Post-FDA Approval: Becoming a Key Therapeutic Option
The NCCN included Rivfloza as a subsequent treatment option for cholangiocarcinoma patients with FGFR2 gene fusions or rearrangements in the updated Biliary Tract Cancer guidelines (Version 2.2026) released on the 8th. This comes just 15 days after the drug received FDA approval on September 23.
The recommendation is classified as "Category 2A," placing it on par with existing FGFR-targeted therapies such as pemigatinib and futibatinib. A Category 2A designation indicates that experts reviewing the clinical evidence are in uniform agreement that the treatment is appropriate.
The NCCN explicitly specifies that Rivfloza, pemigatinib, and futibatinib are recommended ahead of erdafitinib, another FGFR-targeted therapy. While the guidelines do not rank the three primary drugs against one another, the inclusion of Rivfloza alongside established standards is a significant milestone.
[Source: U.S. NCCN, Lirafugratinib listed as a subsequent treatment option in Biliary Tract Cancer guidelines.]
Rivfloza received FDA approval for previously treated patients with FGFR2-positive cholangiocarcinoma. The global Phase 1/2 "ReFocus" trial, which served as the basis for approval, reported an Objective Response Rate (ORR) of approximately 46% and a median duration of response (mDOR) of 11.8 months.
This NCCN listing serves as a crucial foundation for actual clinical adoption in the U.S. The NCCN guidelines are widely used by clinicians in American cancer centers as a primary reference when determining the best treatment plan for patients.
In the U.S., physicians can prescribe anti-cancer drugs even for non-approved indications if there is sufficient medical evidence—a practice known as "off-label" prescribing. Authorized medical resources like the NCCN Compendium often serve as the basis for determining insurance coverage for such off-label uses.
As clinical evidence for other cancer types accumulates, it could lead to broader prescription opportunities. However, the current NCCN recommendation is limited to cholangiocarcinoma; insurance coverage for other cancer types will require separate clinical evidence and regulatory review.
Beyond Cholangiocarcinoma: Rivfloza Pursues the "Tumor-Agnostic" Strategy of Keytruda
HLB's next strategic objective is the development of a "tumor-agnostic" therapy—a method where the treatment targets patients with specific genetic abnormalities, regardless of the organ where the cancer originated.
A prime example is MSD’s immunotherapy, Keytruda. Keytruda has successfully expanded its indications across multiple cancer types and secured approvals as a tumor-agnostic treatment, usable based on specific biomarkers irrespective of tumor location.
Rivfloza is similarly expanding its therapeutic scope by targeting FGFR2 gene abnormalities. As a selective FGFR2 inhibitor, it blocks the abnormal signaling caused by gene fusions or rearrangements. Because FGFR2 abnormalities are found not only in cholangiocarcinoma but also in pancreatic, breast, and other solid tumors, the potential for expanded indications has been long recognized.
Initial clinical results have already shown responses in non-cholangiocarcinoma patients. According to a study published in the journal 'Clinical Cancer Research', an objective response rate of 37% and a median duration of response of 7.3 months were observed in 44 patients with non-cholangiocarcinoma solid tumors harboring FGFR2 rearrangements.
Notably, responses were also confirmed in pancreatic cancer, a condition with historically limited treatment options. In the ReFocus trial presented at the 2023 American Association for Cancer Research (AACR) annual meeting, two out of five pancreatic cancer patients with FGFR2 abnormalities responded to the treatment. While the small sample size warrants caution, these results provided the basis for further validation across other solid tumors.
Building on these early results, HLB’s U.S. subsidiary, Elevar Therapeutics, launched the global Phase 2 "ReFocus202" (NCT07359820) clinical trial this past June. The study aims to evaluate the efficacy and safety of Rivfloza in 30 patients with non-cholangiocarcinoma solid tumors possessing FGFR2 fusions or rearrangements. The first patient dose was administered at Samsung Medical Center.
[Source: ClinicalTrials.gov, Phase 2 tumor-agnostic clinical trial status for Rivfloza.]
According to the U.S. clinical trial registry ClinicalTrials.gov, the primary completion date for ReFocus202 is slated for September 2027. Elevar plans to integrate existing clinical data with new patient results to evaluate at least five patients across seven different cancer types, aiming to confirm whether the therapeutic effect remains consistent across different anatomical origins.
With FDA approval already secured for FGFR2-positive cholangiocarcinoma, positive data in other solid tumors would provide the necessary evidence to pursue further indication expansion.
Having strengthened its U.S. prescription foundation through September's FDA approval and this month's NCCN listing, HLB is now focused on broadening the clinical utility of Rivfloza. The company intends to leverage its success in cholangiocarcinoma to validate the drug's potential in other solid tumors, including pancreatic cancer.
