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

Kura Oncology

Status and phase: Completed; Phase 2; Phase 1

Conditions: HNSCC

Treatments: Drug: Alpelisib; Drug: Tipifarnib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04997902

KO-TIP-013

Details and patient eligibility

About

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.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. At least 18 years of age.
2. 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).
3. Documented treatment failure from at least 1 prior systemic therapy in the R/M setting, unless determined not appropriate.
4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
5. Has a tumor that is dependent upon HRAS and/or PIK3CA.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Acceptable liver, renal, endocrine, and hematologic function.
8. Must be able to swallow alpelisib whole tablet or oral suspension containing crushed tablets. Feeding tube may not be used for alpelisib administration.
9. Other protocol defined inclusion criteria may apply.

Exclusion criteria

1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (eg, mucosal melanoma).
2. Ongoing treatment with certain anticancer agents.
3. Prior treatment (at least 1 full treatment cycle) with an FTI or PI3K, mTOR, or AKT inhibitor.
4. Received treatment for unstable angina, myocardial infarction, and/or cerebro-vascular attack within the prior 6 months.
5. Non-tolerable Grade 2, or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
6. Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
7. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
8. Participant with an established diagnosis of diabetes mellitus Type 1 or not controlled Type 2.
9. Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs based on Investigator discretion.
10. Participant has currently documented pneumonitis/interstitial lung disease.
11. 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).
12. Other protocol defined exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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45 participants in 2 patient groups

PIK3CA-dependent (Cohort 1)

Experimental group

Description:

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

Treatment:

Drug: Tipifarnib

Drug: Alpelisib

HRAS-dependent (Cohort 2)

Experimental group

Description:

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

Treatment:

Drug: Tipifarnib

Drug: Alpelisib