A COMBINATION STUDY OF TIPIFARNIB AND ALPELISIB

NOW ENROLLING FOR PATIENTS WITH HRAS-DEPENDENT AND/OR PIK3CA-DEPENDENT HNSCC

ABOUT KURRENT-HN

KURRENT-HN is a Phase 1/2 open-label, combination, dose escalation study of tipifarnib, a farnesyltransferase inhibitor, and alpelisib, a PI3K inhibitor, to determine the safety and recommended dose and regimen for the treatment of adult patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors overexpress the HRAS protein and/or are PIK3CA-mutated and/or PIK3CA-amplified. The codependency of HRAS and PI3K pathways in driving tumor growth provides the rationale for a combination trial of tipifarnib and alpelisib in this subset of HNSCC patients.¹

ABOUT TIPIFARNIB AND ALPELISIB

Tipifarnib is an oral investigational monotherapy 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^2-4.

Alpelisib is an oral inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. It received FDA approval as PIQRAY^®, a kinase inhibitor indicated in combination with fulvestrant for the treatment of postmenopausal women and men with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen. Important Safety Information can be found here.⁵

HRAS and PI3K Are Complementary Pathways Driving Resistance to Inhibition of Each Other

HRAS Overexpression + PIK3CA Amplification

STUDY OVERVIEW¹

KURRENT-HN is an open-label, combination, dose-escalation study evaluating the safety of the combination of tipifarnib and alpelisib and determining the recommended dosing regimen in recurrent/metastatic HNSCC for adult patients who meet criteria for at least one of two biomarker-defined cohorts:

Tumors harboring PIK3CA mutations and/or amplifications as determined by next-generation sequencing (NGS) on a tumor tissue biopsy (Cohort 1)
Tumors with increased HRAS dependency, defined as HRAS overexpression as determined on a tumor tissue biopsy using immunohistochemistry (IHC) (Cohort 2)

Trial Number: KO-TIP-013
ClinicalTrials.gov Identifier: NCT04997902

PATIENT CRITERIA

KEY INCLUSION CRITERIA¹

At least 18 years of age.
Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal or unknown primary) or squamous histology not amenable to local therapy with curative intent.
Tumor is HRAS-dependent and/or PIK3CA-dependent.
Treatment failure from at least one prior therapy in the R/M setting or considered ineligible for immunotherapy or other first-line standard-of-care options, with the following exception:
- Patient is considered not appropriate for treatment with standard of care in this setting, with documented rationale.
Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Acceptable organ function.

KEY EXCLUSION CRITERIA¹

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, including, but not limited to:
- Uncontrolled diabetes (fasting plasma glucose >140 mg/dL and hemoglobin A1c ≥6.5%)

For full details of inclusion criteria, exclusion criteria, and outcome measures, please visit clinicaltrials.gov.

OUTCOME MEASURES

STUDY LOCATIONS

All 11 /AIM 0 /Arizona 0 /Australia 0 /Austria 0 /Belgium 0 /California 0 /California 0 /California 1 /Currents 0 /Denmark 0 /Florida 0 /Florida 0 /Florida 1 /France 0 /Georgia 0 /Germany 0 /Global 0 /Global 0 /Greece 0 /Illinois 0 /Indiana 0 /Italy 0 /Italy 0 /Kansas 0 /Kentucky 0 /Komet 0 /Kurrent 11 /Leadership In The News 0 /Malaysia 0 /Maryland 0 /Maryland 0 /Maryland 2 /Massachusetts 0 /Massachusetts 0 /Massachusetts 1 /Michigan 0 /Michigan 0 /Minnesota 0 /Minnesota 0 /Missouri 0 /Missouri 1 /Netherlands 0 /New Jersey 0 /New York 0 /New York 0 /New York 1 /North Carolina 0 /North Carolina 0 /Norway 0 /Oklahoma 0 /Pennsylvania 0 /Pennsylvania 0 /Pennsylvania 1 /Republic of Korea 0 /Spain 0 /Spain 0 /Taiwan 0 /Tennessee 0 /Tennessee 0 /Texas 0 /Texas 2 /Thailand 0 /United Kingdom 0 /United States 0 /United States 0 /United States 11 /Washington 0 /Washington 0 /Wisconsin 0 /Wisconsin 1

City of Hope Comprehensive Cancer Center

Duarte, California, United States, 91010

Dana-Farber Cancer Institute (Head and Neck Cancer Treatment Center)

Boston, Massachusetts, United States, 02215

Johns Hopkins University School of Medicine (Sidney Kimmel Comprehensive Cancer Center)

Baltimore, Maryland, United States, 21231

Lake Nona DDU (Florida Cancer Specialists)

Orlando, Florida, United States, 32827

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

University of Maryland School of Medicine (Marlene and Stewart Greenebaum Comprehensive Cancer Center)

Baltimore, Maryland, United States, 21201

For more information, please email: KO-TIP-013@kuraoncology.com.
To connect with a medical science liaison (MSL), please email: medicalaffairs@kuraoncology.com.

REFERENCES

1. National Cancer Institute. What Are Clinical Trials? Reviewed February 4, 2020. Accessed October 19, 2021. www.cancer.gov/aboutcancer/treatment/clinical-trials/what-are-trials 2. Vigneswaran N, Williams MD. Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin North Am. 2014;26(2):123-141. 3. Sung H, Ferlay J, Siegel R, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. 4. American Cancer Society. Cancer Facts & Figures 2021. Atlanta, GA: American Cancer Society; 2021. 5. National Cancer Institute. Head and neck cancers. Reviewed March 29, 2017. Accessed June 17, 2021. https:// www.cancer.gov/types/head-and-neck/head-neck-fact-sheet
6. Malone E, Siu LL. Precision medicine in head and neck cancer: myth or reality? Clin Med Insights Oncol. 2018;12:1179554918779581. 7. Braig F, Voigtlaender M, Schieferdecker A, et al. Liquid biopsy monitoring uncovers acquired RAS-mediated resistance to cetuximab in a substantial proportion of patients with head and neck squamous cell carcinoma. Oncotarget. 2016;7(28):42988-42995. 8. Koontongkaew S. The tumor microenvironment contribution to development, growth, invasion and metastasis of head and neck squamous cell carcinomas. J Cancer. 2013;4(1):66-83. 9. American Cancer Society. Genes and cancer. Revised June 25, 2014. Accessed June 17, 2021. https://www.cancer.org/cancer/cancer-causes/genetics/genesand-cancer.html 10. National Cancer Institute Dictionary of Cancer Terms. Overexpress. Accessed June 17, 2021. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/overexpress 11. Burrows F, Shivani M, Wang Z, et al. Antitumor activity of tipifarnib and PI3K pathway inhibitors in HRASassociated head and neck squamous cell carcinoma. Poster presented at: 32nd EORTC-NCI-AACR Symposium; October 24-25 2020; virtual. 12. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Head and Neck Cancers V.3.2021. ^© National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed October 19, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 13. Cancer.Net. Head and neck cancer: types of treatment. October 2019. Accessed June 17, 2021. https://www.cancer.net/cancer types/headand-neck-cancer/types-treatment 14. American Cancer Society. How chemotherapy drugs work. Revised November 22, 2019. Accessed June 17, 2021. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/how-chemotherapy-drugs-work.html 15. Chow LQM. Head and neck cancer. N Engl J Med. 2020;382(1):60-72.

A COMBINATION STUDY OF TIPIFARNIB AND ALPELISIB

NOW ENROLLING FOR PATIENTS WITH HRAS-DEPENDENT AND/OR PIK3CA-DEPENDENT HNSCC

ABOUT KURRENT-HN

ABOUT TIPIFARNIB AND ALPELISIB

KEY INCLUSION CRITERIA¹

KEY EXCLUSION CRITERIA¹

PRIMARY OUTCOMES¹

SECONDARY OUTCOMES¹

STUDY LOCATIONS

City of Hope Comprehensive Cancer Center

Dana-Farber Cancer Institute (Head and Neck Cancer Treatment Center)

Johns Hopkins University School of Medicine (Sidney Kimmel Comprehensive Cancer Center)

Lake Nona DDU (Florida Cancer Specialists)

Memorial Sloan Kettering Cancer Center

University of Maryland School of Medicine (Marlene and Stewart Greenebaum Comprehensive Cancer Center)

University of Texas MD Anderson Cancer Center

University of Wisconsin Carbone Cancer Center

UPMC Hillman Cancer Center

UT Southwestern Medical Center (Harold C. Simmons Comprehensive Cancer Center)

Washington University, School of Medicine

REFERENCES