A Combination Study of Tipifarnib and Alpelisib

For patients with HRAS-dependent and/or PIK3CA‑dependent HNSCC now enrolling

Learn about the tipifarnib monotherapy trial for patients with HRAS-mutant 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

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Preclinical data

Study locations

IMG_KURCOR_735349 AML Trial Web Pages vs 06

About tipifarnib and alpelisib^2,3

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.

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.⁴

Study Overview¹ Patient Criteria Outcome Measures

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 1 of 2 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

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 1 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.

Primary Outcomes¹

Dose and regimen
Safety and tolerability

Secondary Outcomes¹

Objective response rate
Disease control rate
Pharmacokinetics (PK)
Progression-free survival
Overall survival

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

STUDY LOCATIONS

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All 6 /AIM 0 /Arizona 0 /Australia 0 /Austria 0 /Belgium 0 /California 0 /California 0 /California 1 /Careers 0 /Clinical Development 0 /Clinical Operations 0 /CMC and Supply Chain 0 /Denmark 0 /Diagnostics 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 6 /Malaysia 0 /Maryland 0 /Maryland 0 /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 /News 0 /North Carolina 0 /North Carolina 0 /Norway 0 /Ohio 0 /Oklahoma 0 /Pennsylvania 0 /Pennsylvania 0 /Pennsylvania 1 /Republic of Korea 0 /Russian Federation 0 /Spain 0 /Spain 0 /State 0 /Taiwan 0 /Tennessee 0 /Tennessee 0 /Texas 0 /Texas 0 /Thailand 0 /Ukraine 0 /United Kingdom 0 /United States 0 /United States 0 /United States 6 /Washington 0 /Washington 0 /Wisconsin 0

For more information, please email: KO-TIP-013@kuraoncology.com.

To talk with a medical science liaison (MSL), please email: medicalaffairs@kuraoncology.com.

REFERENCES: 1. Data on file. KURA Oncology Clinical Trial Protocol: KO-TIP-013. March 24, 2021. 2. Gilardi M, Wang Z, Proietto M, et al. Tipifarnib as a precision therapy for HRAS-mutant head and neck squamous cell carcinomas. Mol Cancer Ther. 2020;19(9):1784-1796. 3. Malone E, Siu LL. Precision medicine in head and neck cancer: myth or reality? Clin Med Insights Oncol. 2018;12:1179554918779581. doi:10.1177/1179554918779581 4. PIQRAY. Prescribing information. Novartis Pharmaceuticals Corporation; 2020.

A Combination Study of Tipifarnib and Alpelisib

About KURRENT-HN

About tipifarnib and alpelisib2,3

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)

Lake Nona DDU (Florida Cancer Specialists)

Memorial Sloan Kettering Cancer Center

UPMC Hillman Cancer Center

Washington University, School of Medicine

CORPORATE HEADQUARTERS

About tipifarnib and alpelisib^2,3

Key Inclusion Criteria¹

Key Exclusion Criteria¹

Primary Outcomes¹

Secondary Outcomes¹