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HNSCCPhase 1/2NCT04997902

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

A Phase 1/2 study testing Tipifarnib and Alpelisib in people with HNSCC, run by Kura Oncology, Inc. at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HNSCC
What is being tested?
Tipifarnib and Alpelisib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
11 sitesUnited States
Study dates
7 Dec 2021to 29 Aug 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Other protocol defined inclusion criteria may apply.

Who cannot join

  • 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.
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  • 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).
  • Other protocol defined exclusion criteria may apply.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

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

    Baltimore, Maryland, 21201

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

    Baltimore, Maryland, 21231

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

    Boston, Massachusetts, 02215

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

    Dallas, Texas, 75390

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Lake Nona DDU (Florida Cancer Specialists)

    Orlando, Florida, 32827

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Washington University, School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase 1/2 Open-label, Biomarker-defined Cohort Trial to Evaluate the Safety, Determine the Recommended Combination Dosing, and Assess Early Antitumor Activity of Tipifarnib and Alpelisib for the Treatment of Adult Participants Who Have HRAS-overexpressing and/or PIK3CA-mutated and/or - Amplified Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

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
Being tested
Tipifarnib, Alpelisib
Keywords
HRAS, PIK3CA, PI3K, Tipifarnib, Alpelisib, R/M HNSCC (Recurrent/metastatic Head and Neck Squamous Cell Carcinoma), Head and Neck Cancer, SCCHN
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Hereditary Sensory and Autonomic Neuropathies, Recurrence, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TipifarnibDrug

    Oral administration

  • AlpelisibDrug

    Also called BYL719

    Oral administration

Study groups in NCT04997902
Study groupRoleWhat they receive
PIK3CA-dependent (Cohort 1)ExperimentalAdult participants with R/M HNSCC whose tumors harbor PI3KCA (activating) mutations and/or amplifications
Receives: Drug: Tipifarnib; Drug: Alpelisib
HRAS-dependent (Cohort 2)ExperimentalAdult participants with R/M HNSCC whose tumors have increased HRAS dependency, defined as HRAS overexpression
Receives: Drug: Tipifarnib; Drug: Alpelisib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity (DLT)

    Rate of DLTs evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. A Treatment-Emergent Adverse Event (TEAE) is an AE occurring on or after Cycle 1 Day 1 and within 30 days of the last dose of tipifarnib or alpelisib, whichever is later. Patients with multiple events are counted only once at the highest CTCAE grade.

    Measured: First 28 days (1 cycle) of combination therapy

  2. 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. AEs are coded using the MedDRA dictionary version 28.0. A TEAE is an AE occurring on or after Cycle 1 Day 1 and within 30 days of the last dose of tipifarnib or alpelisib, whichever is later. At each level of summation (system organ class, preferred term), a patient reporting more than one adverse event is counted only once.

    Measured: 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)

  1. Objective Response Rate (ORR)

    Defined as the proportion of participants with best overall response as a confirmed complete response (CR) or confirmed partial response (PR) by RECIST v1.1. Clopper-Pearson 95% confidence intervals are calculated based on binomial distribution.

    Measured: 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

  2. Median duration of response

    Defined for participants with confirmed objective response as the time from the first documentation of response to the first documentation of disease progression by RECIST v1.1 or to death due to any cause before new anti-cancer treatment, whichever occurs first. Median is calculated using Kaplan-Meier method. Confidence interval for median is calculated using the Brookmeyer-Crowley method. Minimum and maximum are actual values rather than estimates.

    Measured: 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

  3. Disease control rate (DCR)

    Disease control rate (CR + PR + SD)

    Measured: 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

  4. Median duration of Disease Control

    Defined for participants with confirmed objective response as the time in months from the first documentation of response to the first documentation of disease progression by RECIST v1.1 or to death due to any cause before new anti-cancer treatment, whichever occurs first, in patients with confirmed CR/PR

    Measured: 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

  5. Rate of Stable Disease

    Measured: 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

  6. Median duration of Stable Disease (SD)

    Defined as durable SD (>= 12 weeks) by RECIST v1.1

    Measured: 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

  7. Cmax of tipifarnib and alpelisib when administered in combination

    Maximum observed concentration following single dose and multiple dose administration

    Measured: Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.

  8. Tmax of tipifarnib and alpelisib when administered in combination

    Time to reach maximum observed concentration following single dose and multiple dose administration

    Measured: Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.

  9. AUC(0-last) of tipifarnib and alpelisib when administered in combination

    Area under the concentration-time curve from time zero to time of last quantifiable concentration following single dose and multiple dose administration

    Measured: Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.

  10. AUC(tau) of tipifarnib and alpelisib when administered in combination

    Area under the concentration-time curve during a dosage interval following single dose and multiple dose administration

    Measured: Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.

  11. AUC(0-infinity) of tipifarnib and alpelisib when administered in combination

    Area under the concentration-time curve from time zero to infinity following single dose administration

    Measured: Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.

  12. CL/F of tipifarnib and alpelisib when administered in combination

    Apparent total clearance of the drug following single dose and multiple dose administration

    Measured: Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.

  13. Vd/F of tipifarnib and alpelisib when administered in combination

    Apparent volume of distribution following single dose and multiple dose administration

    Measured: Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.

  14. Half-life of tipifarnib and alpelisib when administered in combination

    Time required for the amount of drug in the body to decrease by half following single dose and multiple dose administration

    Measured: Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.

  15. Accumulation ratio of tipifarnib and alpelisib when administered in combination

    Defined as the ratio of drug exposure at steady state to exposure following a single dose. For tipifarnib, the accumulation ratio was calculated as the ratio of area under the plasma concentration-time curve over the dosing interval (AUCτ) on Cycle 2 Day 1 (C2D1) to AUC from time zero to 12 hours (AUC₀-12) on Cycle 1 Day 1 (C1D1). For alpelisib, the accumulation ratio was calculated as the ratio of AUCτ on C2D1 to AUC from time zero to 24 hours (AUC₀-24) on C1D1.

    Measured: Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.

  16. Progression-free survival (PFS)

    Defined as the time in months from C1D1 to the first documentation of disease progression or death due to any cause before new anti-cancer treatment. Median is calculated using Kaplan-Meier method. Confidence interval for median is calculated using the Brookmeyer-Crowley method. Minimum and maximum are actual values rather than estimates.

    Measured: 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 3 years

  17. Proportion of participants with PFS at 6 months

    Proportion of participants alive and without disease progression at 6 months and before new anti-cancer treatment. Survival probability and confidence interval are calculated based on Kaplan-Meier product-limit method and Greenwood's formula.

    Measured: 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 6 months

  18. Overall Survival (OS)

    OS is the time in months from C1D1 to the date of death due to any cause. For patients with no events, OS will be censored at the last known to be alive date. Median is calculated using Kaplan-Meier method. Confidence interval for median is calculated using the Brookmeyer-Crowley method. Minimum and maximum are actual values rather than estimates.

    Measured: From Cycle 1 Day 1 until 3 years of treatment or death from any cause, whichever comes first

  19. Proportion of patients with OS at 12 months

    Proportion of participants alive at 12 months. For patients with no events, OS will be censored at the last known to be alive date. Survival probability and confidence interval are calculated based on Kaplan-Meier product-limit method and Greenwood's formula.

    Measured: From Cycle 1 Day 1 until 12 months of treatment or death from any cause, whichever comes first

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2021
  2. Study start7 Dec 2021
  3. Primary completion29 Aug 2025
  4. Study completion29 Aug 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04997902
Sponsor's protocol ID
KO-TIP-013
Status last verified
Aug 2026
First submitted
27 Jul 2021
Last updated
8 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tipifarnib and Alpelisib in people with HNSCC, run by Kura Oncology, Inc. at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity (DLT) (time frame: First 28 days (1 cycle) of combination therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04997902.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2026.

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