Reference Detail

Ref Type

Abstract

PMID

Authors

A. Hollebecque, M. Borad, L. Goyal, A. Schram, J.O. Park, P.A. Cassier, S.D. Kamath, D.T. Wai Meng, E. Dotan, R. Kim, V. Sahai, D. Oh, C. Liao, M. Millward, D. Roda Perez, C. Ferté, R. Blakesley, B. Wolf18, V. Subbiah, R.K. Kelley

Title

Efficacy of RLY-4008, a highly selective FGFR2 inhibitor in patients (pts) with an FGFR2-fusion or rearrangement (f/r), FGFR inhibitor (FGFRi)-naïve cholangiocarcinoma (CCA): ReFocus trial

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	33	Supplement 7	Sep 11, 2022

URL

https://www.annalsofoncology.org/article/S0923-7534(22)03884-4/fulltext

Abstract Text

Background Previous, nonselective FGFRi have validated FGFR2 f/r as a target in CCA by achieving an objective response rate (ORR) of ∼20-40% with duration of response (DOR) ∼5-9 months. However, off-target toxicity and emergence of polyclonal FGFR2 resistance limit their efficacy. RLY-4008 is the first highly selective, potent FGFR2 inhibitor designed to target both driver alterations and FGFR resistance mutations. Here we present the initial efficacy of RLY-4008 in pts with a FGFR2 f/r, FGFRi-naïve CCA. Methods ReFocus (RLY-4008-101), a Phase 1/2 study (NCT04526106), enrolled pts with advanced solid tumors who received RLY-4008 orally (20-200 mg QD or BID). FGFR2 f/r status was determined by local testing. Key objectives were investigator-assessed ORR per RECIST v1.1, DOR, and safety. Safety was analyzed in all dosed pts and efficacy in pts with FGFR2 f/r, FGFRi-naïve CCA with measurable disease and an opportunity for ≥2 tumor assessments to confirm response. Results As of 01AUG22, 38 pts with FGFR2 f/r, FGFRi naïve CCA were efficacy evaluable. Most pts received the recommended phase 2 dose (RP2D); most (68%) remain on treatment with median duration of 6 months (<0.1 - 18.5 months). Potent efficacy was observed across all doses, particularly at the RP2D with an ORR of 88% (Table). One pt treated at the RP2D had a near-complete response and subsequent tumor resection with curative intent. DOR is not yet mature, with majority of responses ongoing. Across all doses (N=195), the most common treatment-related AEs (TRAEs) were low-grade stomatitis (48%), PPE (46%), and dry mouth (31%). No grade 4/5 TRAEs were observed. Table: 000LBA12

Filtering

Case insensitive filtering will display rows if any text in any cell matches the filter term
Use simple literal full or partial string matches
Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
Click on any column header arrows to sort by that column
Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References