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 mutations^2,4

STUDY OVERVIEW

AIM-HN is an international, multicenter, open-label, registration-directed study evaluating the efficacy and tolerability of tipifarnib in relapsed or refractory HRAS-mutant HNSCC.

Trial Number: KO-TIP-007
ClinicalTrials.gov Identifier: NCT03719690

PATIENT CRITERIA

KEY INCLUSION CRITERIA

At least 18 years of age.
Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal or unknown primary) of squamous histology not amenable to local therapy with curative intent.
Documented treatment failure from most recent prior therapy (eg, tumor progression, clinical deterioration or recurrence) and at least one prior platinum-containing regimen, in any treatment setting. The most recent prior and platinum-based therapy may be the same regimen.
Known tumor missense HRAS mutation.
Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Acceptable organ function.

KEY EXCLUSION CRITERIA

Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (eg, mucosal melanoma).
Concomitant disease or condition that could interfere with the conduct of the study or that would, in the opinion of the investigator, pose an unacceptable risk to the patient in this study.

OUTCOME MEASURES

STUDY LOCATIONS

All 93 /AIM 93 /Arizona 0 /Australia 2 /Austria 2 /Belgium 5 /California 3 /California 0 /California 0 /Currents 0 /Denmark 2 /Florida 2 /Florida 0 /Florida 0 /France 0 /Georgia 1 /Germany 4 /Global 70 /Global 0 /Greece 3 /Illinois 0 /Indiana 0 /Italy 7 /Italy 0 /Kansas 1 /Kentucky 2 /Komet 0 /Kurrent 0 /Leadership In The News 0 /Malaysia 2 /Maryland 2 /Maryland 0 /Maryland 0 /Massachusetts 1 /Massachusetts 0 /Massachusetts 0 /Michigan 1 /Michigan 0 /Minnesota 1 /Minnesota 0 /Missouri 1 /Missouri 0 /Netherlands 3 /New Jersey 0 /New York 2 /New York 0 /New York 0 /North Carolina 1 /North Carolina 0 /Norway 2 /Oklahoma 1 /Pennsylvania 1 /Pennsylvania 0 /Pennsylvania 0 /Republic of Korea 8 /Spain 15 /Spain 0 /Taiwan 7 /Tennessee 1 /Tennessee 0 /Texas 0 /Texas 0 /Thailand 3 /United Kingdom 5 /United States 23 /United States 0 /United States 0 /Washington 1 /Washington 0 /Wisconsin 1 /Wisconsin 0

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.

A MONOTHERAPY FARNESYLTRANSFERASE INHIBITOR STUDY

FOR PATIENTS WITH HRAS-MUTANT HNSCC

ABOUT AIM-HN

ABOUT TIPIFARNIB

FARNESYLATION IS AN ESSENTIAL MODIFICATION REQUIRED FOR HRAS ACTIVITY

HRAS MUTATIONS IN HNSCC

STUDY LOCATIONS

Allgemeines Krankenhaus der Stadt Wien

Asan Medical Center

Azienda Ospedaliera S. Croce e Carle Cuneo

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

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant’Orsola-Malpighi

Barbara Ann Karmanos Cancer Institute

Bioclinic – Thessaloniki

Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne

Chang Gung Medical Foundation Keelung Chang Gung Memorial Hospital

Chang Gung Memorial Hospital

Changhua Christian Hospital

Charité Universitätsmedizin Berlin

China Medical University Hospital

Chonbuk National University Hospital

Cliniques Universitaires Saint-Luc

Complejo Hospitalario de Navarra

Dana Farber Cancer Institute

Fondazione IRCCS – Istituto Nazionale dei Tumori – Milano

Fox Chase Cancer Center

Greater Baltimore Medical Center

Hanusch Krankenhaus Wiener Gebietskrankenkasse

Haukeland Universitetssjukehus

Herlev Hospital

HM Centro Integral Oncológico Clara Campal

Hospital Clinic i Provincial de Barcelona

Hospital Clínico Universitario de Santiago de Compostela

Hospital Costa Del Sol

Hospital de la Santa Creu i de Sant Pau

Hospital del Mar – Parc de Salut Mar

Hospital Duran i Reynals

Hospital Universitari i Politecnic La Fe de Valencia

Hospital Universitari Vall d’Hebrón

Hospital Universitario 12 de Octubre

Hospital Universitario La Paz

Hospital Universitario Miguel Servet

Hospital Universitario Virgen de la Victoria

Hospital Universitario Virgen del Rocio

Institut Kanser Negara

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

King Chulalongkorn Memorial Hospital

Korea University Anam Hospital

Levine Cancer Institute

Maastricht University Medical Centre

Mackay Memorial Hospital

Maharaj Nakorn Chiang Mai Hospital

Marlene and Stewart Greenebaum Cancer Center

Mayo Clinic

Memorial Sloan Kettering Cancer Center

Miami Cancer Institute

National Cancer Center

National Cheng Kung University Hospital

National Taiwan University Hospital

New York University Langone Medical Center

NHS Greater Glasgow and Clyde

Norton Cancer Institute

Ospedale Mater Salutis di Legnago

Peter MacCallum Cancer Centre

Radiumhospitalet

Rigshospitalet

Royal North Shore Hospital

Samsung Medical Center

Seattle Cancer Care Alliance

Siteman Cancer Center – Washington University Medical Campus

Songklanagarind Hospital

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

The Catholic University of Korea St. Vincent’s Hospital

The Christie NHS Foundation Trust

The Oncology Institute of Hope and Innovation – Anaheim

The Royal Marsden NHS Foundation Trust

The Royal Marsden NHS Foundation Trust

UCLA – Jonsson Comprehensive Cancer Center

UCSF – Helen Diller Family Comprehensive Cancer Center