Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
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...
Tipifarnib is an investigational small molecule being developed by Kura Oncology for multiple oncology indications, including thyroid cancer, head and neck squamous cell carcinoma (HNSCC), HRAS gene mutation tumors, chronic myelomonocytic leukemia, and relapsed or refractory peripheral T-cell lymphoma. It is currently in Phase 1 clinical development.
Tipifarnib is a small molecule that targets HRAS, a gene frequently mutated in certain cancers. By inhibiting HRAS activity, it aims to disrupt cancer cell growth and survival. This targeted approach is being studied in tumors with HRAS mutations, such as head and neck squamous cell carcinoma.
Tipifarnib is being developed by Kura Oncology, Inc., a biopharmaceutical company focused on precision medicine for cancer. Kura Oncology is publicly traded under the ticker symbol KURA on the Nasdaq stock exchange.
Tipifarnib is currently in Phase 1 clinical development. While earlier Phase 2 studies have been completed, the most recent trial, a combination study with alpelisib in head and neck squamous cell carcinoma, is a Phase 1 trial. Tipifarnib is investigational and not yet approved by regulatory authorities.
Tipifarnib has been studied in several clinical trials. Notable trials include NCT02383927, a Phase 2 study in squamous head and neck cancer with HRAS mutations; NCT02807272 in chronic myelomonocytic leukemia; NCT03719690 in head and neck cancer with HRAS mutations; and NCT04997902, a Phase 1 combination trial with alpelisib in recurrent or metastatic HNSCC.
Tipifarnib is a distinct investigational drug and is not known to be the same as any other approved medication. It is a farnesyltransferase inhibitor that specifically targets HRAS-mutant tumors, differentiating it from other cancer therapies in development.