Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper session 2: GI, upper digestive

LBA12 - 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

Date

11 Sep 2022

Session

Proffered Paper session 2: GI, upper digestive

Topics

Targeted Therapy

Tumour Site

Hepatobiliary Cancers

Presenters

Antoine Hollebecque

Citation

Annals of Oncology (2022) 33 (suppl_7): S808-S869. 10.1016/annonc/annonc1089

Authors

A. Hollebecque1, M. Borad2, L. Goyal3, A. Schram4, J.O. Park5, P.A. Cassier6, S.D. Kamath7, D.T. Wai Meng8, E. Dotan9, R. Kim10, V. Sahai11, D. Oh12, C. Liao13, M. Millward14, D. Roda Perez15, C. Ferté16, R. Blakesley17, B. Wolf18, V. Subbiah19, R.K. Kelley20

Author affiliations

  • 1 Ditep, Institut Gustave Roussy, 94805 - Villejuif, Cedex/FR
  • 2 Oncology Department, Mayo Clinic Cancer Center, 85259 - Scottsdale/US
  • 3 Medical Oncology, Massachusetts General Hospital, Boston/US
  • 4 Medicine Department, MSKCC - Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 5 Medical Oncology, Samsung Medical Center (SMC) - Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 6 Medical Oncology Department, Centre Léon Bérard, 69008 - Lyon/FR
  • 7 Gastrointestinal Oncology, Taussig Cancer Center-Cleveland Clinic, 44195 - Cleveland/US
  • 8 Medical Oncology, National Cancer Centre Singapore, Singapore/SG
  • 9 Medical Oncology, Fox Chase Cancer Center - Main Campus, 19111-2497 - Philadelphia/US
  • 10 Gi Oncology Dept, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 33612 - Tampa/US
  • 11 Medical Oncology, Michigan Medicine, University of Michigan, 48109 - Ann Arbor/US
  • 12 Internal Medicine Dept., Seoul National University Hospital, 110-744 - Seoul/KR
  • 13 Medicine - Hematology/oncology Section, University of Chicago Department of Medicine - Section of Hematology/Oncology, 60637-1470 - Chicago/US
  • 14 School Of Medicine, Linear Clinical Research & University of Western Australia, 6009 - Perth/AU
  • 15 Oncology Department, Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 16 Scientific Communications, Relay Therapeutics, Inc., 02139 - Cambridge/US
  • 17 Biostatistics, Relay Therapeutics, Inc., 02139 - Cambridge/US
  • 18 Precision Medicine, Relay Therapeutics, Inc., 02139 - Cambridge/US
  • 19 Investigational Cancer Therapeutics Department, The University of Texas M. D. Anderson Cancer Center, 77030 - Houston/US
  • 20 Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, 94143 - San Francisco/US
More

Resources

Login to access the resources on OncologyPRO.

Abstract LBA12

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

RP2D (70 mg QD)N=17 All dose levelsN=38
ORR, n (% [95% CI]) 15 (88.2 [63.6 - 98.5]) 24 (63.2 [46.0 - 78.2])
Confirmed ORR, n (% [95% CI]) 14 (82.4 [56.6 - 96.2]) 22 (57.9 [40.8 - 73.7])
Response ongoing, n/N (%) 15/15 (100.0) 19/24 (79.2)
Disease control rate, n (%) 17 (100.0) 36 (94.7)
Remain on treatment, n (%) 15 (88.2) 26 (68.4)

Conclusions

RLY-4008 is a promising next-generation inhibitor with potential to transform the treatment of FGFR2 f/r, FGFRi-naïve CCA. Pivotal testing continues in ReFocus.

Clinical trial identification

NCT04526106.

Editorial acknowledgement

Legal entity responsible for the study

Relay Therapeutics.

Funding

Relay Therapeutics.

Disclosure

A. Hollebecque: Financial Interests, Personal, Advisory Board: Amgen, BMS, Bailea, Incyte, Servier, QED Therapeutics, Tahio, Relay Therapeutics. M. Borad: Financial Interests, Institutional, Funding: Relay Therapeutics. L. Goyal: Financial Interests, Personal, Advisory Role: Alentis Therapeutics, Genentech, Exelixis, Incyte, QED Therapeutics, Servier, Sirtex, Taiho, Alentis, Black Diamond, H3Biomedicine, Transthera, Kinnate; Financial Interests, Institutional, Funding: Adaptimmune, Bayer, Eisai, Merck, Macrogenics, Genentech, Novartis, Incyte, Eli Lilly, Loxo Oncology, Relay Therapeutics, QED Therapeutics, Servier, Taiho, LEAP Therapeutics, BMS, Nucana. A. Schram: Financial Interests, Institutional, Funding: Relay Therapeutics, AstraZeneca, ArQule, BeiGene/Springworks, Black Diamond Therapeutics, Elevation Oncology, Kura, Lilly, Merus, Northern Biologics, Pfizer, PMV Pharma, Repare Therapeutics, Revolution Medicine, Surface Oncology; Financial Interests, Personal, Advisory Board: Relay Therapeutics, Mersana. J.O. Park: Non-Financial Interests, Personal, Other: BMS/Celgene, Servier; Financial Interests, Personal, Other: MedPacto, ABL Bio; Financial Interests, Personal, Advisory Role: AstraZeneca, Servier, MedPacto. P.A. Cassier: Financial Interests, Personal, Invited Speaker: ITeos, Amgen, Janssen; Financial Interests, Personal, Advisory Role: OSE Immunotherapeutics; Financial Interests, Institutional, Funding: Bayer, GSK, Janssen, Lilly, AstraZeneca, Roche/Genentech, Merck Serono, Toray Industries, Novartis, Plexxikon, BMS, Taiho Pharmaceutical, Transgene, Innate Pharma, Loxo, Blueprint Medicines, Celgene, AbbVie, Merck Sharp & Dohme; Financial Interests, Personal, Netris Pharma, Amgen, Merck Sharp & Dohme, AstraZeneca/MedImmune. S.D. Kamath: Financial Interests, Personal, Advisory Board: Exelixis, Guardant Health, Tempus. D.T. Wai Meng: Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Advisory Role: Novartis, Celgene, Sirtex, MSD, Eisai, Ipsen, Bayer, BMS; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai, BMS, Roche; Financial Interests, Personal, Other: AstraZeneca. E. Dotan: Non-Financial Interests, Personal, Other: Relay Therapeutics; Financial Interests, Institutional, Funding: Lilly, Pfizer, Incyte, AstraZeneca, SMP Oncology, Zymeworks, NGM Biopharmaceuticals, Ipsen, Syneos Health; Financial Interests, Personal, Advisory Role: QED, Taiho, Helsinn, Incyte, Basilea, SMP Oncology, G1 Therapeutics; Financial Interests, Personal, Invited Speaker: Pfizer. R. Kim: Financial Interests, Personal, Advisory Role: Bayer, Elelixis, Lilly, QED Therapeutics, Servier, Taiho Oncology; Financial Interests, Personal, Speaker’s Bureau: Incyte, LIlly; Financial Interests, Institutional, Funding: Bayer, BMS, Eisai. D. Oh: Financial Interests, Institutional, Funding: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA. C. Liao: Financial Interests, Personal, Advisory Board: Incyte, Transthera, QED Therapeutics. M. Millward: Financial Interests, Institutional, Funding: Relay Therapeutics; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, The Limbic, Roche, BMS, Takeda Pharmaceuticals, Guardant Health, BeiGene, Amgen Australia, Merck, Lilly Australia; Financial Interests, Personal, Invited Speaker: BMS, Roche, The Limbic; Financial Interests, Personal, Other, travel: AstraZeneca; Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Leadership Role: Melanoma & Skin Cancer Trials Australia. C. Ferté: Financial Interests, Personal, Stocks/Shares: Relay Therapeutics. R. Blakesley: Financial Interests, Personal, Stocks/Shares: Relay Therapeutics; Financial Interests, Personal, Full or part-time Employment: Relay Therapeutics. B. Wolf: Financial Interests, Personal, Stocks/Shares: Relay Therapeutics; Financial Interests, Personal, Leadership Role: Relay Therapeutics; Financial Interests, Personal, Full or part-time Employment: Relay Therapeutics. V. Subbiah: Financial Interests, Institutional, Funding: Relay Therapeutics. R.K. Kelley: Financial Interests, Institutional, Advisory Role: Exelixis, Agios, AstraZeneca, Ipsen; Financial Interests, Personal, Advisory Role: Genentech/Roche, Kinnate, Exact Sciences; Financial Interests, Institutional, Funding: Bayer, BMS, Agios, AstraZeneca, Eli Lilly, EMD Serono, Ipsen, Loxo Oncology, MSD, QED Therapeutics, Partner Therapeutics, Relay Therapeutics, Surface Oncology. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.