A MONOTHERAPY FARNESYLTRANSFERASE INHIBITOR STUDY

FOR PATIENTS WITH HRAS-MUTANT HNSCC

  • The FDA has granted Breakthrough Therapy Designation for tipifarnib for the treatment of patients with recurrent or metastatic HRAS-mutant HNSCC with variant allele frequency ≥ 20% after disease progression on platinum-based chemotherapy.

ABOUT AIM-HN

AIM-HN is a registration-directed study designed to evaluate the efficacy and tolerability of tipifarnib in HRAS-mutant head and neck squamous cell carcinoma (HNSCC).

ABOUT TIPIFARNIB

Tipifarnib is an oral investigational drug candidate for HRAS-mutant HNSCC. In preclinical models, tipifarnib blocks the activity of an enzyme called farnesyltransferase (FT). It is the only farnesyltransferase inhibitor (FTI) under investigation for HRAS-dependent HNSCC.

FARNESYLATION IS AN ESSENTIAL MODIFICATION REQUIRED FOR HRAS ACTIVITY

  • RAS proteins — which include HRAS, NRAS and KRAS — undergo a series of post-translational modifications.1
  • FT is involved in the first post-translational modification step called prenylation.1
  • FT helps attach a farnesyl group to localize the HRAS protein to the inner cell membrane, allowing it to function in cell signaling pathways.2
  • When FT is inhibited, KRAS and NRAS can use the alternative pathway to achieve prenylation but HRAS cannot.2
  • It is believed that FT inhibitors targeted to HRAS can prevent growth of HRAS-driven tumors.3

HRAS MUTATIONS IN HNSCC

have HRAS mutations2,4

STUDY LOCATIONS

Allgemeines Krankenhaus der Stadt Wien

Wien, Austria, 1090

Arkhangelsk Clinical Oncology Center, Department of Chemotherapy

Arkhangelsk, Russian Federation, 163045

Asan Medical Center

Seoul, Korea, Republic of, 05505

Azienda Ospedaliera S. Croce e Carle Cuneo

Cuneo, Italy, 12100

Azienda Ospedaliera Universitaria Senese-L’ospedale Santa Maria alle Scotte

Siena, Italy, 53100

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant’Orsola-Malpighi

Bologna, Italy, 40138

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

Bioclinic – Thessaloniki

Thessaloniki, Greece, 54622

Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne

Yvoir, Namur, Belgium, 5530

Chang Gung Medical Foundation Keelung Chang Gung Memorial Hospital

Keelung, Taiwan, 20442

Chang Gung Memorial Hospital

Taoyuan, Taiwan, 33305

Changhua Christian Hospital

Changhua, Taiwan, 500

Charité Universitätsmedizin Berlin

Berlin, Germany, 12203

Chelyabinsk Regional Clinical Oncology and Nuclear Medicine Center

Chelyabinsk, Russian Federation, 454087

Chernihiv Medical Center of Modern Oncology, Department of Head and Neck Tumors and Reconstructive Surgery

Chernihiv, Ukraine, 14029

China Medical University Hospital

Taichung, Taiwan, 40447

Chonbuk National University Hospital

Jeonju, Korea, Republic of, 54907

Clinical Hospital #1, Department of Maxillofacial Surgery

Sterlitamak, Republic Of Bashkortostan, Russian Federation, 453120

Clinical Oncology Center, Chemotherapy Department for Children and Adults

Omsk, Russian Federation, 644046

Cliniques Universitaires Saint-Luc

Brussels, Belgium, 1200

Communal Non-Profit Enterprise “Regional Center of Oncology”, Head and Neck Oncosurgery Department

Kharkiv, Ukraine, 61070

Communal Noncommercial Enterprise of Lviv Regional Council “Lviv Regional Clinical Hospital”, Surgery Department #1

Lviv, Ukraine, 79010

Complejo Hospitalario de Navarra

Pamplona, Spain, 31008

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02115

Fondazione IRCCS – Istituto Nazionale dei Tumori – Milano

Milano, Italy, 20133

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

Greater Baltimore Medical Center

Baltimore, Maryland, United States, 21204

Hadassah Medical LTD

Moscow, Russian Federation

Hanusch Krankenhaus Wiener Gebietskrankenkasse

Wien, Austria, 1140

Haukeland Universitetssjukehus

Bergen, Norway, 1521

Herlev Hospital

Herlev, Denmark, 2730

HM Centro Integral Oncológico Clara Campal

Madrid, Spain, 28050

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain, 08036

Hospital Clínico Universitario de Santiago de Compostela

Santiago De Compostela, Spain, 15707

Hospital Costa Del Sol

Marbella, Spain, 29603

Hospital de la Santa Creu i de Sant Pau

Barcelona, Spain, 08025

Hospital del Mar – Parc de Salut Mar

Barcelona, Spain, 08003

Hospital Duran i Reynals

Barcelona, Spain, 08908

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Spain, 46026

Hospital Universitari Vall d’Hebrón

Barcelona, Spain, 08035

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario La Paz

Madrid, Spain, 28046

Hospital Universitario Miguel Servet

Zaragoza, Spain, 50009

Hospital Universitario Virgen de la Victoria

Málaga, Spain, 29010

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

Institut Kanser Negara

Putrajaya, Malaysia, 62250

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, Italy, 80131

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Italy, 47014

Ivanovo Regional Oncology Center

Ivanovo, Russian Federation, 153040

King Chulalongkorn Memorial Hospital

Bangkok, Thailand, 10330

Korea University Anam Hospital

Seoul, Korea, Republic of, 02841

Krasnoyarsk A.I. Kryzhanovsky Regional Oncology Center, Chemotherapy Department

Krasnoyarsk, Russian Federation, 660133

Levine Cancer Institute

Charlotte, North Carolina, United States, 28204

Maastricht University Medical Centre

Maastricht, Netherlands, 6229 HX

Mackay Memorial Hospital

Taipei, Taiwan, 10099

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, Thailand, 50200

Marlene and Stewart Greenebaum Cancer Center

Baltimore, Maryland, United States, 21287

Mayo Clinic

Rochester, Minnesota, United States, 55905

Medical Center “MEDICAL PLAZA” of “ECODNIPRO” LLC

Dnipro, Ukraine, 49000

Medical Center ONCOLIFE, LLC

Zaporizhzhia, Ukraine, 69059

Medical Center VERUM, LLC

Kyiv, Ukraine, 03039

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Miami Cancer Institute

Miami, Florida, United States, 33176

N.N. Petrov National Medical Research Center of Oncology, Head and Neck Surgery Department

St. Petersburg, Russian Federation, 197758

National Cancer Center

Goyang-si, Korea, Republic of, 10408

National Cheng Kung University Hospital

Tainan, Taiwan, 70403

National Medical Research Center for Oncology, Department of General Oncology and Chemotherapy

Rostov-on-Don, Russian Federation, 344037

National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, Department of Chemotherapy

Moscow, Russian Federation, 125284

National Taiwan University Hospital

Taipei, Taiwan, 100

New York University Langone Medical Center

New York, New York, United States, 10016

NHS Greater Glasgow and Clyde

Glasgow, United Kingdom, G12 0XH

Norton Cancer Institute

Louisville, Kentucky, United States, 40202

Oncology Center #2

Sochi, Krasnodar Region, Russian Federation

Oncology Center of Moskovskiy District, Oncology Department

St. Petersburg, Russian Federation, 196247

Ospedale Mater Salutis di Legnago

Legnago, Italy, 37045

Peter MacCallum Cancer Centre

Melbourne, Australia, 3000

Private Medical Institution “EVROMEDSERVIS”

St. Petersburg, Russian Federation, 196603

Prykarpattia Clinical Oncology Center under Ivano-Frankivsk Regional Council, Surgery Department #2

Ivano-Frankivsk, Ukraine, 76018

Public Enterprise “Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital” under Dnipropetrovsk Regional Council, Department of Otolaryngology #2 (oncologic)

Dnipro, Ukraine, 49005

Public Non-Profit Enterprise Ternopil Regional Clinical Oncology Center, Department of Chemotherapy

Ternopil, Ukraine, 46023

Pyatigorsk Interdistrict Oncology Center

Pyatigorsk, Russian Federation, 357502

Radiumhospitalet

Oslo, Norway, 0379

Railway Clinical Hospital under OAO Russian Railways

St. Petersburg, Russian Federation, 195271

Regional Clinical Oncology Hospital, Department of Chemotherapy

Yaroslavl, Russian Federation, 150040

Regional Public Non-Profit Enterprise “Bukovyna Clinical Oncology Center”, Day Care Unit

Chernivtsi, Ukraine, 58013

Republican Clinical Oncology Center, Chemotherapy Department, Head and Neck Oncosurgery Department

Ufa, Russian Federation, 450054

Rigshospitalet

Copenhagen, Denmark, 2100

Royal North Shore Hospital

Saint Leonards, Australia, 2065

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

Siteman Cancer Center – Washington University Medical Campus

Saint Louis, Missouri, United States, 63129

Songklanagarind Hospital

Hat Yai, Thailand, 90110

State Organization “Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine”, Department of Clinical Oncology and Hematology

Kharkiv, Ukraine, 61024

Sumy Regional Clinical Oncology Center, Oncothoracic Department

Sumy, Ukraine, 40022

The Catholic University of Korea – Seoul St. Mary’s Hospital

Seoul, Korea, Republic of, 06591

The Catholic University of Korea St. Vincent’s Hospital

Suwon, Korea, Republic of, 16247

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

The Oncology Institute of Hope and Innovation – Anaheim

Whittier, California, United States, 90603

The Royal Marsden NHS Foundation Trust

Sutton, United Kingdom, SM2 5PT

The Royal Marsden NHS Foundation Trust

London, United Kingdom, SW3 6JJ

UCLA – Jonsson Comprehensive Cancer Center

Los Angeles, California, United States, 90095

UCSF – Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States, 94158

Universitair Medisch Centrum Groningen

Groningen, Netherlands, 9713 GZ

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands, 3584 CX

Universitair Ziekenhuis Antwerpen

Edegem, Belgium, 2650

Universitair Ziekenhuis Leuven

Leuven, Belgium, 3000

Universitätsklinikum Leipzig

Leipzig, Germany, 04103

Universitätsklinikum Würzburg

Würzburg, Germany, 97080

Universitätsmedizin Mannheim

Mannheim, Germany, 68167

University College London Hospitals NHS Foundation Trust

London, United Kingdom, NW1 2BU

University General Hospital of Athens Attikon

Chaidari, Greece, 12462

University General Hospital of Larissa

Larissa, Greece, 41110

University Malaya Medical Centre

Kuala Lumpur, Malaysia, 59100

University Of Kansas Medical Center

Westwood, Kansas, United States, 66205

University of Kentucky Markey Cancer Center

Lexington, Kentucky, United States, 40536

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States, 73104

University of South Florida H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States, 33612

University of Wisconsin

Madison, Wisconsin, United States, 53705

Vanderbilt University Medical Center-Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States, 37232

Winship Cancer Institute

Atlanta, Georgia, United States, 30322

Yonsei University Health System Severance Hospital

Seoul, Korea, Republic of, 03722

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerpen, Belgium, 2020

For more information, please email: KO-TIP-007@kuraoncology.com.
To connect with a medical science liaison (MSL), please email: medicalaffairs@kuraoncology.com.

REFERENCES

  • 1. Ahearn IM, Haigis K, Bar-Sagi D, Philips MR. Regulating the Regulator: Post-Translational Modification of Ras. Nat Rev Mol Cell Biol. 2012;13(1):39-51. 2. Malone E, Siu LL. Precision Medicine in Head and Neck Cancer: Myth or Reality? Clin Med Insights Oncol. 2018;12:1-7. 3. Gilardi M, Wang Z, Proietto M, et al. (In press). Tipifarnib as a Precision Therapy for HRAS-Mutant Head and Neck Squamous Cell Carcinomas. 2020. 4. The Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576-582.