Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

NCT04997902 | Completed Phase 1 FDA Drug

• 1 other identifier: KO-TIP-013
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 11

Brief Summary

This phase 1/2 combination trial of tipifarnib, a farnesyltransferase inhibitor, and alpelisib, a PI3K inhibitor in participants 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.

Conditions

HNSCC

Keywords

HRAS; PIK3CA; PI3K; Tipifarnib; Alpelisib; R/M HNSCC (Recurrent/metastatic Head and Neck Squamous Cell Carcinoma); Head and Neck Cancer; SCCHN

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  Rate of DLTs per dose level

  First 28 days (1 cycle) of combination therapy

• Descriptive statistics of Adverse Events (AEs)

  Descriptive statistics of Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs; AE severity will be assessed per the NCI CTCAE v 5.0

  From Cycle 1 Day 1 until 30 days after last trial intervention dose or 30 days after trial completion, whichever comes first, assessed up to 2 years

Secondary Outcomes (19)

• Objective Response Rate (ORR)

  From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years

• Median duration of response

  From first documentation of response to first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years

• Disease control rate (DCR)

  From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years

• Median duration of Disease Control

  From first documentation of response until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years

• Rate of Stable Disease

  From Cycle 1 Day 1 until first documentation of disease progression, the start of new anti-cancer therapy, or death, whichever occurs first, assessed up to 2 years

Study Arms (2)

PIK3CA-dependent (Cohort 1)

EXPERIMENTAL

Adult participants with R/M HNSCC whose tumors harbor PI3KCA (activating) mutations and/or amplifications

Drug: Tipifarnib; Drug: Alpelisib

HRAS-dependent (Cohort 2)

EXPERIMENTAL

Adult participants with R/M HNSCC whose tumors have increased HRAS dependency, defined as HRAS overexpression

Drug: Tipifarnib; Drug: Alpelisib

Interventions

Tipifarnib DRUG

Oral administration

HRAS-dependent (Cohort 2); PIK3CA-dependent (Cohort 1)

Alpelisib DRUG

Oral administration

Also known as: BYL719

HRAS-dependent (Cohort 2); PIK3CA-dependent (Cohort 1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age.
• Histologically confirmed head and neck cancer of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
• Documented treatment failure from at least 1 prior systemic therapy in the R/M setting, unless determined not appropriate.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Has a tumor that is dependent upon HRAS and/or PIK3CA.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Acceptable liver, renal, endocrine, and hematologic function.
• Must be able to swallow alpelisib whole tablet or oral suspension containing crushed tablets. Feeding tube may not be used for alpelisib administration.

You may not qualify if:

• Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (eg, mucosal melanoma).
• Ongoing treatment with certain anticancer agents.
• Prior treatment (at least 1 full treatment cycle) with an FTI or PI3K, mTOR, or AKT inhibitor.
• Received treatment for unstable angina, myocardial infarction, and/or cerebro-vascular attack within the prior 6 months.
• Non-tolerable Grade 2, or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
• Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
• Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
• Participant with an established diagnosis of diabetes mellitus Type 1 or not controlled Type 2.
• Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs based on Investigator discretion.
• Participant has currently documented pneumonitis/interstitial lung disease.
• Participant has a history of severe cutaneous reaction, such as Stevens-Johnson Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Sponsors & Collaborators

• Kura Oncology, Inc.: lead

Study Sites (11)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Lake Nona DDU (Florida Cancer Specialists)

Orlando, Florida, 32827, United States

Location

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

Baltimore, Maryland, 21201, United States

Location

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

Baltimore, Maryland, 21231, United States

Location

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

Boston, Massachusetts, 02215, United States

Location

Washington University, School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

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

Dallas, Texas, 75390, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Hereditary Sensory and Autonomic Neuropathies; Recurrence; Head and Neck Neoplasms

Interventions

tipifarnib; Alpelisib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: August 10, 2021
• Study Start: December 7, 2021
• Primary Completion: July 30, 2025
• Study Completion: July 30, 2025
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

US (11)