Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as R115777, Zarnestra, Zarnesta
Tipifarnib · 5 trials · 8 indications
ORR was defined as the percentage of participants who experienced a best overall response (BOR) of complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by IRF. 95% confidence interval (CI) was calculated by the exact binomial (Clopper-Pearson) method.
The ORR was estimated based on the number of participants who achieved an objective response (OR) (complete response \[CR\], complete cytogenetic remission \[CCR\], partial remission \[PR\], marrow response \[MR\], or clinical benefit \[CB\] performed by Principal Investigator according to the MDS/MPN International Working Group \[IWG\] criteria).
The ORR of tipifarnib was response assessments according to RECIST 1.1. The estimate of the ORR was calculated based on the maximum likelihood estimator (i.e., crude percentage of subjects whose best overall response was complete response \[CR\] or partial response \[PR\]). The estimate of the ORR was accompanied by 2-sided 95% confidence interval (CI). The 95% CI was estimated using the Wilson score test-based method. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.
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.
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.
| Arm | Type | Description |
|---|---|---|
| AIM-HN | EXPERIMENTAL | Tipifarnib, Oral Tablet. Dose Level 1 orally, bid on days 1-7 and 15-21 of 28-day treatment cycles |
| SEQ-HN | NO_INTERVENTION | HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up. |
| Tipifarnib, Oral | EXPERIMENTAL | Single arm |
| Tipifarnib | EXPERIMENTAL | tipifarnib, oral |
| Cohort 1 | EXPERIMENTAL | Thyroid Cancer |
| Cohort 2 | EXPERIMENTAL | Squamous Head and Neck Cancer |
| PIK3CA-dependent (Cohort 1) | EXPERIMENTAL | Adult participants with R/M HNSCC whose tumors harbor PI3KCA (activating) mutations and/or amplifications |
| HRAS-dependent (Cohort 2) | EXPERIMENTAL | Adult participants with R/M HNSCC whose tumors have increased HRAS dependency, defined as HRAS overexpression |
| Name | Type | Description |
|---|---|---|
| Tipifarnib | DRUG | Tablet for oral administration |
| HRAS Detection Assay | DEVICE | In Vitro Assay to detect HRAS mutations |
| Alpelisib | DRUG | Oral administration |
Inclusion Criteria: AIM-HN 1. At least 18 years of age. 2. Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or with...
Top 3 of 4 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Tango Therapeutics, Inc. | TNGX | 1 | PHASE1 | TNG462 |
| Pasithea Therapeutics Corp. | KTTA | 1 | PHASE1 | PAS-004 |
| Adlai Nortye Ltd. Sponsored ADR | ANL | 1 | PHASE1 | AN9025 |
Tipifarnib is an investigational oral small molecule being studied in several cancers, including head and neck squamous cell carcinoma (HNSCC), HRAS-mutant head and neck cancer, chronic myelomonocytic leukemia, relapsed or refractory peripheral T-cell lymphoma, and thyroid cancer. It is being developed by Kura Oncology, Inc. (ticker: KURA) and remains in clinical development.
Tipifarnib targets farnesyltransferase enzymes FNTA and FNTB. It acts as an inhibitor of these enzymes. Farnesyltransferase catalyzes the addition of a farnesyl group to proteins such as RAS, a modification required for their membrane localization and signaling activity. By inhibiting FNTA and FNTB, tipifarnib interferes with this prenylation step.
Tipifarnib is being developed by Kura Oncology, Inc., which trades on the Nasdaq under the ticker symbol KURA. Kura Oncology is the sponsor of the clinical trials evaluating tipifarnib across head and neck cancer, chronic myelomonocytic leukemia, peripheral T-cell lymphoma, and other oncology indications.
Tipifarnib is in clinical development and is not approved. Its trials span Phase 1 and Phase 2. A Phase 1 combination trial of tipifarnib plus alpelisib in recurrent or metastatic head and neck squamous cell carcinoma has completed, and several Phase 2 studies in HRAS-mutant head and neck cancer, chronic myelomonocytic leukemia, and peripheral T-cell lymphoma have also completed.
Tipifarnib has been evaluated in completed studies including NCT04997902, a Phase 1 combination trial with alpelisib in recurrent or metastatic HNSCC; NCT03719690, a Phase 2 trial in HRAS-mutant head and neck cancer; NCT02807272, a Phase 2 trial in chronic myelomonocytic leukemia and related myeloid neoplasms; and NCT02464228, a Phase 2 trial in relapsed or refractory peripheral T-cell lymphoma.
Tipifarnib has been studied in head and neck squamous cell carcinoma, including tumors with HRAS gene mutations, chronic myelomonocytic leukemia, relapsed or refractory peripheral T-cell lymphoma, and thyroid cancer. These programs fall within oncology, and the clinical trials have enrolled adult patients across sites in the United States and multiple other countries.