Therapy Detail
Contact
Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
| Therapy Name | Tipifarnib |
| Synonyms | |
| Therapy Description |
Zarnestra (tipifarnib) is a farnesyltransferase inhibitor, which alters post-translational modification and activation of Ras proteins, and may result in decreased tumor cell proliferation and reduced tumor growth (PMID: 11196150, PMID: 25323927, PMID: 32557577). |
Filtering
- Case insensitive filtering will display rows if any text in any cell matches the filter term
- Use simple literal full or partial string matches
- Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
- Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
- Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")
Sorting
- Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
- Click on any column header arrows to sort by that column
- Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.
| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Tipifarnib | Zarnestra|R115777 | Farnesyltransferase Inhibitor 4 | Zarnestra (tipifarnib) is a farnesyltransferase inhibitor, which alters post-translational modification and activation of Ras proteins, and may result in decreased tumor cell proliferation and reduced tumor growth (PMID: 11196150, PMID: 25323927, PMID: 32557577). |
Filtering
- Case insensitive filtering will display rows if any text in any cell matches the filter term
- Use simple literal full or partial string matches
- Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
- Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
- Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")
Sorting
- Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
- Click on any column header arrows to sort by that column
- Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| HRAS Q61L | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a head and neck squamous cell carcinoma cell line xenograft model harboring HRAS Q61L was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth and vessel formation, increased apoptotic activity, and decreased cell proliferation (PMID: 32727882). | 32727882 |
| HRAS mutant | salivary gland cancer | predicted - sensitive | Tipifarnib | Phase II | Actionable | In a Phase II trial (KO-TIP-001), Zarnestra (tipifarnib) treatment resulted in an objective response rate of 8% (1/12) in patients with recurrent or metastatic salivary gland cancer harboring HRAS mutations, with a median progression-free survival of 7 months (J Clin Oncol 38: 2020 (suppl; abstr 6504); NCT02383927). | detail... |
| HRAS G13R | Advanced Solid Tumor | sensitive | Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, expression of HRAS G13R in an HRAS-null, NRAS-null, and KRAS knockout cell line conferred sensitivity to Zarnestra (tipifarnib) in culture, resulting in decreased cell viability (PMID: 39152269). | 39152269 |
| HRAS A146T | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Pdx | Actionable | In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS A146T was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). | 32727882 |
| HRAS G13R | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Pdx | Actionable | In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS G13R was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). | 32727882 |
| HRAS mutant | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Phase II | Actionable | In a Phase II trial (AIM-HN), Zarnestra (tipifarnib) demonstrated safety and preliminary activity in patients with recurrent or metastatic head and neck squamous cell carcinoma harboring mutations in HRAS, resulting in an objective response rate of 20% (10/50, 1 complete and 9 partial responses), disease control rate of 48% (24/50), with stable disease in 14 patients, median progression-free survival of 2.6 mo, and median overall survival of 7 mo (Ann Oncol (2023) 34 (suppl_2): S1286-S1287; NCT03719690). | detail... |
| HRAS mutant | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, head and neck squamous cell carcinoma cell lines harboring an HRAS mutation were sensitive to treatment with Zarnestra (tipifarnib), demonstrating reduced cell growth and decreased phosphorylation of Erk and Mek, and inhibition of spheroid viability in culture (PMID: 32727882). | 32727882 |
| HRAS mutant | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Phase II | Actionable | In a Phase II trial (KO-TIP-001), Zarnestra (tipifarnib) treatment resulted in an objective response rate of 55% (11/20) in patients with head and neck squamous cell carcinoma harboring HRAS missense mutations at a variant allele frequency over 20%, with nine patients achieved stable disease and a median progression-free survival of 5.6 months (PMID: 33750196; NCT02383927). | 33750196 |
| HRAS G12S | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Pdx | Actionable | In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS G12S was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). | 32727882 |
| HRAS G12S | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Case Reports/Case Series | Actionable | In a clinical case study, Zarnestra (tipifarnib) treatment resulted in a partial response that lasted for 8 months in a patient with ear canal squamous cell carcinoma harboring HRAS G12S (PMID: 38219706). | 38219706 |
| HRAS G13R | renal pelvis transitional cell carcinoma | predicted - sensitive | Tipifarnib | Case Reports/Case Series | Actionable | In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, a patient with renal pelvis transitional cell carcinoma harboring HRAS G13R achieved a partial response (PMID: 32636318; NCT02535650). | 32636318 |
| HRAS G12V | head and neck squamous cell carcinoma | sensitive | Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, Zarnestra (tipifarnib) treatment led to decreased cell viability and inhibition of clonogenic and anchorage-independent growth in a head and neck squamous cell carcinoma cell line harboring HRAS G12V in culture (PMID: 35247914). | 35247914 |
| HRAS G13V PIK3CA E545K | salivary gland carcinoma | predicted - sensitive | Tipifarnib | Case Reports/Case Series | Actionable | In a clinical case study, Zarnestra (tipifarnib) treatment resulted in a partial response and progression-free survival lasting more than 5 months in a patient with androgen-receptor (AR)-positive salivary duct carcinoma harboring HRAS G13V and PIK3CA E545K (PMID: 37427101). | 37427101 |
| HRAS act mut | transitional cell carcinoma | predicted - sensitive | Tipifarnib | Phase II | Actionable | In a Phase II trial, Zarnestra (tipifarnib) demonstrated safety and preliminary efficacy in patients with metastatic urothelial carcinoma harboring HRAS mutations (n=14) or STK11:rs2075606, 3 of 4 patients achieved progression-free survival at 6 months harbored HRAS activating mutations, and no response was observed in HRAS wild-type patients (J Clin Oncol 38: 2020 (suppl; abstr 5086); NCT02535650). | detail... |
| HRAS G12S | renal pelvis transitional cell carcinoma | predicted - sensitive | Tipifarnib | Case Reports/Case Series | Actionable | In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, a patient with renal pelvis transitional cell carcinoma harboring HRAS G12S achieved a partial response (PMID: 32636318; NCT02535650). | 32636318 |
| HRAS K117N | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Pdx | Actionable | In a preclinical study, a head and neck squamous cell carcinoma patient-derived xenograft (PDX) model harboring HRAS K117N was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth, decreased cell proliferation, and reduced Erk activity (PMID: 32727882). | 32727882 |
| HRAS act mut | salivary gland carcinoma | sensitive | Tipifarnib | Clinical Study | Actionable | In a clinical study, Zarnestra (tipifarnib) treatment resulted in an overall response rate of 8% (n=13) with one ongoing partial response with a duration of 14 months and stable disease as the best response in 58% (7/12) of evaluable patients with HRAS-mutant metastatic salivary gland carcinoma, and a median overall survival of 18 months, and a median progression-free survival of 7 months (PMID: 32557577). | 32557577 |
| HRAS Q61R | bladder urothelial carcinoma | predicted - sensitive | Tipifarnib | Case Reports/Case Series | Actionable | In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, 2 patients with bladder urothelial carcinoma harbored HRAS Q61R achieved partial responses (PMID: 32636318; NCT02535650). | 32636318 |
| HRAS G12D | head and neck squamous cell carcinoma | sensitive | Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, Zarnestra (tipifarnib) treatment led to decreased cell viability and inhibition of clonogenic and anchorage-independent growth in head and neck squamous cell carcinoma cell lines harboring HRAS G12D in culture (PMID: 35247914). | 35247914 |
| HRAS over exp | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Pdx | Actionable | In a preclinical study, Zarnestra (tipifarnib) treatment resulted in tumor regression in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma overexpressing wild-type Hras (J Clin Oncol 38: 2020 (suppl; abstr e15658)). | detail... |
| HRAS G12C | head and neck squamous cell carcinoma | predicted - sensitive | Tipifarnib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a head and neck squamous cell carcinoma cell line xenograft model harboring HRAS G12C was sensitive to treatment with Zarnestra (tipifarnib), demonstrating inhibition of tumor growth and vessel formation, increased apoptotic activity, and decreased cell proliferation (PMID: 32727882). | 32727882 |
| HRAS mutant | transitional cell carcinoma | predicted - sensitive | Tipifarnib | Phase II | Actionable | In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS missense (Q61R, G12S, G13R) or frameshift (V29Cfs*19) mutations, progression-free survival was significantly improved in patients harboring HRAS mutations (5.1 vs 0.8 months, HR=0.262) compared to wild-type patients (PMID: 32636318; NCT02535650). | 32636318 |
| HRAS V29Cfs*19 | bladder urothelial carcinoma | predicted - sensitive | Tipifarnib | Case Reports/Case Series | Actionable | In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS mutations, a patient with bladder urothelial carcinoma harboring HRAS V29Cfs*19 achieved a partial response (PMID: 32636318; NCT02535650). | 32636318 |
| HRAS G13R PIK3CA H1047R | Advanced Solid Tumor | resistant | Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R and PIK3CA H1047R were resistant to Zarnestra (tipifarnib) in culture (PMID: 39152269). | 39152269 |
| BRAF G466E HRAS G13R | Advanced Solid Tumor | sensitive | Tipifarnib | Preclinical - Cell culture | Actionable | In a preclinical study, HRAS-null, NRAS-null, and KRAS knockout cells expressing HRAS G13R and BRAF G466E were sensitive to Zarnestra (tipifarnib) in culture, demonstrating decreased cell viability (PMID: 39152269). | 39152269 |
Filtering
- Case insensitive filtering will display rows if any text in any cell matches the filter term
- Use simple literal full or partial string matches
- Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
- Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
- Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")
Sorting
- Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
- Click on any column header arrows to sort by that column
- Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT02383927 | Phase II | Tipifarnib | Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations | Completed | USA | NLD | ITA | GRC | GBR | FRA | ESP | DEU | BEL | 1 |
| NCT03719690 | Phase II | Tipifarnib | Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy (AIM-HN/SEQ-HN) | Completed | USA | NOR | NLD | ITA | GRC | GBR | ESP | DNK | DEU | BEL | AUT | AUS | 4 |
| NCT02464228 | Phase II | Tipifarnib | Study of Tipifarnib in Subjects With Relapsed or Refractory Peripheral T-Cell Lymphoma | Completed | USA | ESP | 1 |
| NCT04284774 | Phase II | Tipifarnib | Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial | Active, not recruiting | USA | 1 |
| NCT00006199 | Phase I | Tipifarnib Topotecan | Study of the Farnesyl Transferase Inhibitor, R115777, in Combination With Topotecan (NYU 99-32) | Unknown status | USA | 0 |
| NCT02807272 | Phase II | Tipifarnib | Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia (CMML) | Completed | USA | 0 |
| NCT02779777 | Phase II | Tipifarnib | Tipifarnib in Subjects With Transfusion-dependent, Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes | Terminated | USA | 0 |
| NCT03496766 | Phase II | Tipifarnib | Tipifarnib in Advanced Squamous NSCLC With Oncogen HRAS MutAtionS | Terminated | ESP | 0 |
CKB BOOST