Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
An international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN). The first cohort will assess the objective response rate (ORR) of tipifarnib in subjects with HNSCC with HRAS mutations. The second study cohort, SEQ-HN, is an observational sub-study including 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.
KO-TIP-007 is an international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN) and the impact of HRAS mutations on response to first line systemic therapies for HNSCC (SEQ-HN). KO-TIP-007 has 2 study cohorts. The first study cohort, named AIM-HN, includes HNSCC subjects with HRAS mutations. AIM-HN subjects will receive treatment with tipifarnib and the outcome of this cohort will be evaluated for ORR by an independent review facility.
The second study cohort, SEQ-HN, is an observational sub-study including 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.
HNSCC patients in whom HRAS mutations are identified and who meet eligibility criteria will be offered participation in AIM-HN. HNSCC patients in whom HRAS mutations are not identified may participate in SEQ-HN only. These patients will be followed and the comparison of outcomes of HRAS mutant and HRAS wild type HNSCC will address the exploratory objective to determine the effect of HRAS mutation on the ORR of first line systemic therapy in patients with recurrent/metastatic HNSCC. Outcome data from subsequent lines of therapy will be collected.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tipifarnib | Drug | Tablet for oral administration |
| |
| HRAS Detection Assay |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF) | 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. | Up to approximately 28 months |
| Measure | Description | Time Frame |
|---|---|---|
| ORR in All VAF Population, as Assessed by IRF | ORR was defined as the percentage of participants who experienced a BOR of CR or PR and was assessed using RECIST v1.1 by IRF. 95% CI was calculated by the exact binomial (Clopper-Pearson) method. | Up to approximately 28 months |
| Duration of Response (DoR) in High VAF Population, as Assessed by IRF |
Not provided
Inclusion Criteria:
AIM-HN
Exclusion Criteria:
Inclusion Criteria: SEQ-HN
Exclusion Criteria: SEQ-HN
1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
5. Other protocol defined exclusion criteria may apply
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Southern California Norris Comprehensive Cancer Center | Los Angeles | California | 90033 | United States | ||
This study consisted of 2 non-comparative sub-studies: (1) an interventional open-label, single-arm, pivotal study evaluating the efficacy of tipifarnib in mHRAS HNSCC (AIM-HN) and (2) an observational study to evaluate the impact of HRAS mutations on response to first line systemic therapies for HNSCC (SEQ-HN).
A total of 296 participants were enrolled (59 participants in AIM-HN and 237 participants in SEQ-HN) in 14 countries between March 2019 and May 2023.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Tipifarnib Treatment Cohort: AIM-HN | Participants enrolled as part of AIM-HN received tipifarnib administered with food at a starting dose of 600 mg, orally, twice a day (bid) on Days 1-7 and 15-21 of 28-day cycles. |
| FG001 | Observational Cohort: SEQ-HN |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 9, 2020 | Apr 18, 2024 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Device |
In Vitro Assay to detect HRAS mutations |
|
DoR was defined as the time from the date of first response (CR or PR [whichever occurred first]) to the date of progression of disease or death of any cause, whichever occurred first, in participants with a confirmed CR or PR and was assessed using RECIST v1.1 by IRF. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. |
| Up to approximately 28 months |
| DoR in All VAF Population, as Assessed by IRF | DoR was defined as the time from the date of first response (CR or PR [whichever occurred first]) to the date of progression of disease or death of any cause, whichever occurred first, in participants with a confirmed CR or PR and was assessed using RECIST v1.1 by IRF. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | Up to approximately 28 months |
| Progression Free Survival (PFS) in High VAF Population, as Assessed by IRF | PFS was defined as months from the first dose of the study drug to the first documented progressive disease (PD, appearance of one or more new lesions or at least a 20% increase in the sum of the diameters of target lesions) or death, whichever came first and was assessed using RECIST v1.1 by IRF. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | Up to approximately 28 months |
| PFS in All VAF Population, as Assessed by IRF | PFS was defined as months from the first dose of the study drug to the first documented PD or death, whichever came first and was assessed using RECIST v1.1 by IRF. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | Up to 28 approximately months |
| PFS Rate in High VAF Population, as Assessed by IRF | PFS rate was defined as the percentage of participants who had not experienced documented PD or death, whichever came first and was assessed using RECIST v1.1 by IRF at 6 and 9 month timepoints. Percentage of participants was calculated using the Kaplan-Meier method. 95% CI was calculated using normal approximation to the log transformed cumulative hazard rate | 6 months and 9 months |
| PFS Rate in All VAF Population, as Assessed by IRF | PFS rate was defined as the percentage of participants who had not experienced documented PD or death, whichever came first and was assessed using RECIST v1.1 by IRF at 6 and 9 month timepoints. Percentage of participants was calculated using the Kaplan-Meier method. 95% CI was calculated using normal approximation to the log transformed cumulative hazard rate. | 6 months and 9 months |
| Overall Survival (OS) in High VAF Population | OS was defined as months from first dose date until death from any cause. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | Up to approximately 28 months |
| OS in All VAF Population | OS was defined as months from first dose date until death from any cause. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | Up to approximately 28 months |
| OS Rate at 12 Months in High VAF Population | OS rate was defined as the percentage of participants who had not experienced or death and was assessed at 12 months. Percentage of participants was calculated using the Kaplan-Meier method. 95% CI was calculated using normal approximation to the log transformed cumulative hazard rate. | 12 months |
| OS Rate at 12 Months in All VAF Population | OS rate was defined as the percentage of participants who had not experienced or death and was assessed at 12 months. Percentage of participants was calculated using the Kaplan-Meier method. 95% CI was calculated using normal approximation to the log transformed cumulative hazard rate. | 12 months |
| Time to Response (TTR) in High VAF Population, as Assessed by IRF | TTR was defined as months from treatment start to first CR or PR (whichever was first recorded) in participants with confirmed CR or PR and was assessed using RECIST v1.1 by IRF. TTR was summarized descriptively by summary statistics. | Up to approximately 28 months |
| TTR in All VAF Population, as Assessed by IRF | TTR was defined as months from treatment start to first CR or PR (whichever was first recorded) in participants with confirmed CR or PR and was assessed using RECIST v1.1 by IRF. TTR was summarized descriptively by summary statistics. | Up to approximately 28 months |
| Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | TEAEs were defined as adverse events (AEs) that started on or after the first dose of the study drug and within 30 days of the last administration of the study drug. Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was used for toxicity grading (Grade 3: severe or disabling; Grade 4: life-threatening; Grade 5: death related to AE). Clinically significant changes in laboratory tests, vital signs, and electrocardiogram results were reported as AEs. | Up to approximately 28 months |
| Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module 35 (EORTC QLQ-H&N35) Subscales | Change from Baseline score in pain, swallowing, speech problems, and senses problems subscales of EORTC QLQ-H&N35 are summarized individually. Raw scores for each subscale were linear transformations and standardized to range (0 - 100), with higher scores representing worse levels of symptoms. Change from Baseline was calculated as End of Treatment Observed - Baseline with a negative change representing a reduction in symptoms. | Baseline and End of Treatment Visit (up to approximately 28 months) |
| Change From Baseline in the EuroQol-Visual Analog Scale (EQ-VAS) Score | The EQ-VAS forms part of the EQ-5D-5L and collects the self-rating health status from 0 (the worst imaginable health) to 100 (the best imaginable health). Change from Baseline was calculated as End of Treatment Observed - Baseline with a negative change representing an increase in symptoms. | Baseline and End of Treatment Visit (up to approximately 28 months) |
| UCLA - Jonsson Comprehensive Cancer Center |
| Los Angeles |
| California |
| 90095 |
| United States |
| UCSF - Helen Diller Family Comprehensive Cancer Center | San Francisco | California | 94158 | United States |
| The Oncology Institute of Hope and Innovation - Anaheim | Whittier | California | 90603 | United States |
| Miami Cancer Institute | Miami | Florida | 33176 | United States |
| University of South Florida H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612 | United States |
| Winship Cancer Institute | Atlanta | Georgia | 30322 | United States |
| University of Chicago | Chicago | Illinois | 60637 | United States |
| University Of Kansas Medical Center | Westwood | Kansas | 66205 | United States |
| University of Kentucky Markey Cancer Center | Lexington | Kentucky | 40536 | United States |
| Norton Cancer Institute | Louisville | Kentucky | 40202 | United States |
| Greater Baltimore Medical Center | Baltimore | Maryland | 21204 | United States |
| Marlene and Stewart Greenebaum Cancer Center | Baltimore | Maryland | 21287 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| Barbara Ann Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Siteman Cancer Center - Washington University Medical Campus | St Louis | Missouri | 63129 | United States |
| New York University Langone Medical Center | New York | New York | 10016 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Levine Cancer Institute | Charlotte | North Carolina | 28204 | United States |
| The Ohio State University | Columbus | Ohio | 43210 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| Fox Chase Cancer Center | Philadelphia | Pennsylvania | 19111 | United States |
| Vanderbilt University Medical Center-Vanderbilt Ingram Cancer Center | Nashville | Tennessee | 37232 | United States |
| San Antonio Military Medical Center | Fort Sam Houston | Texas | 78234 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| University of Texas Health San Antonio - Mays Cancer Center | San Antonio | Texas | 78229 | United States |
| Seattle Cancer Care Alliance | Seattle | Washington | 98109 | United States |
| University of Wisconsin | Madison | Wisconsin | 53705 | United States |
| Peter MacCallum Cancer Centre | Melbourne | 3000 | Australia |
| Royal North Shore Hospital | Saint Leonards | 2065 | Australia |
| Allgemeines Krankenhaus der Stadt Wien | Vienna | 1090 | Austria |
| Hanusch Krankenhaus Wiener Gebietskrankenkasse | Vienna | 1140 | Austria |
| Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne | Yvoir | Namur | 5530 | Belgium |
| Ziekenhuis Netwerk Antwerpen Middelheim | Antwerp | 2020 | Belgium |
| Cliniques Universitaires Saint-Luc | Brussels | 1200 | Belgium |
| Universitair Ziekenhuis Antwerpen | Edegem | 2650 | Belgium |
| Universitair Ziekenhuis Leuven | Leuven | 3000 | Belgium |
| Rigshospitalet | Copenhagen | 2100 | Denmark |
| Herlev Hospital | Herlev | 2730 | Denmark |
| Charité Universitätsmedizin Berlin | Berlin | 12203 | Germany |
| Universitätsklinikum Leipzig | Leipzig | 04103 | Germany |
| Universitätsmedizin Mannheim | Mannheim | 68167 | Germany |
| Universitätsklinikum Würzburg | Würzburg | 97080 | Germany |
| University General Hospital of Athens Attikon | Chaïdári | 12462 | Greece |
| University General Hospital of Larissa | Larissa | 41110 | Greece |
| Bioclinic - Thessaloniki | Thessaloniki | 54622 | Greece |
| Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi | Bologna | 40138 | Italy |
| Azienda Ospedaliera S. Croce e Carle Cuneo | Cuneo | 12100 | Italy |
| Ospedale Mater Salutis di Legnago | Legnago | 37045 | Italy |
| Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Meldola | 47014 | Italy |
| Fondazione IRCCS - Istituto Nazionale dei Tumori - Milano | Milan | 20133 | Italy |
| Istituto Nazionale Tumori IRCCS Fondazione Pascale | Naples | 80131 | Italy |
| Azienda Ospedaliera Universitaria Senese-L'ospedale Santa Maria alle Scotte | Siena | 53100 | Italy |
| University Malaya Medical Centre | Kuala Lumpur | 59100 | Malaysia |
| Institut Kanser Negara | Putrajaya | 62250 | Malaysia |
| Universitair Medisch Centrum Groningen | Groningen | 9713 GZ | Netherlands |
| Maastricht University Medical Centre | Maastricht | 6229 HX | Netherlands |
| Universitair Medisch Centrum Utrecht | Utrecht | 3584 CX | Netherlands |
| Haukeland Universitetssjukehus | Bergen | 1521 | Norway |
| Radiumhospitalet | Oslo | 0379 | Norway |
| National Cancer Center | Goyang-si | 10408 | South Korea |
| Chonbuk National University Hospital | Jeonju | 54907 | South Korea |
| Korea University Anam Hospital | Seoul | 02841 | South Korea |
| Yonsei University Health System Severance Hospital | Seoul | 03722 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Samsung Medical Center | Seoul | 06351 | South Korea |
| The Catholic University of Korea - Seoul St. Mary's Hospital | Seoul | 06591 | South Korea |
| The Catholic University of Korea St. Vincent's Hospital | Suwon | 16247 | South Korea |
| Hospital del Mar - Parc de Salut Mar | Barcelona | 08003 | Spain |
| Hospital de la Santa Creu i de Sant Pau | Barcelona | 08025 | Spain |
| Hospital Universitari Vall d'Hebrón | Barcelona | 08035 | Spain |
| Hospital Clinic i Provincial de Barcelona | Barcelona | 08036 | Spain |
| Hospital Duran i Reynals | Barcelona | 08908 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | 28041 | Spain |
| Hospital Universitario La Paz | Madrid | 28046 | Spain |
| HM Centro Integral Oncológico Clara Campal | Madrid | 28050 | Spain |
| Hospital Costa Del Sol | Marbella | 29603 | Spain |
| Hospital Universitario Virgen de la Victoria | Málaga | 29010 | Spain |
| Complejo Hospitalario de Navarra | Pamplona | 31008 | Spain |
| Hospital ClÃnico Universitario de Santiago de Compostela | Santiago de Compostela | 15707 | Spain |
| Hospital Universitario Virgen del Rocio | Seville | 41013 | Spain |
| Hospital Universitari i Politecnic La Fe de Valencia | Valencia | 46026 | Spain |
| Hospital Universitario Miguel Servet | Zaragoza | 50009 | Spain |
| Changhua Christian Hospital | Changhua | 500 | Taiwan |
| Kaohsiung Chang Gung Memorial Hospital | Kaohsiung City | 83301 | Taiwan |
| Chang Gung Medical Foundation Keelung Chang Gung Memorial Hospital | Keelung | 20442 | Taiwan |
| China Medical University Hospital | Taichung | 40447 | Taiwan |
| Taichung Veterans General Hospital | Taichung | 407 | Taiwan |
| National Cheng Kung University Hospital | Tainan | 70403 | Taiwan |
| Mackay Memorial Hospital | Taipei | 10099 | Taiwan |
| National Taiwan University Hospital | Taipei | 100 | Taiwan |
| Chang Gung Memorial Hospital | Taoyuan | 33305 | Taiwan |
| King Chulalongkorn Memorial Hospital | Bangkok | 10330 | Thailand |
| Maharaj Nakorn Chiang Mai Hospital | Chiang Mai | 50200 | Thailand |
| Songklanagarind Hospital | Hat Yai | 90110 | Thailand |
| Guy's and Saint Thomas' NHS Foundation Trust | London | England | SE1 9RT | United Kingdom |
| NHS Greater Glasgow and Clyde | Glasgow | G12 0XH | United Kingdom |
| University College London Hospitals NHS Foundation Trust | London | NW1 2BU | United Kingdom |
| The Royal Marsden NHS Foundation Trust | London | SW3 6JJ | United Kingdom |
| The Christie NHS Foundation Trust | Manchester | M20 4BX | United Kingdom |
| The Royal Marsden NHS Foundation Trust | Sutton | SM2 5PT | United Kingdom |
Participants with HNSCC in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consented to provide first line outcome data and additional follow-up. |
| Safety Analysis Set (SAS) |
|
| Modified Intent-to-Treat Analysis Set (mITT) |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
All enrolled participants.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Tipifarnib Treatment Cohort: AIM-HN | Participants enrolled as part of AIM-HN received tipifarnib administered with food at a starting dose of 600 mg, orally, bid on Days 1-7 and 15-21 of 28-day cycles. |
| BG001 | Observational Cohort: SEQ-HN | Participants with HNSCC in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consented to provide first line outcome data and additional follow-up. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Variant Allele Frequency (VAF) Status | Genetic testing was done for tumor tissue to confirm mutant (variant) allele frequency at Baseline. | Data collection and analysis of VAF status for participants in the Observational SEQ-HN Cohort was not pre-specified. | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF) | 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. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for participants with high VAF only. Data collection and analysis of ORR for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to approximately 28 months |
|
|
| |||||||||||||||||||||||||
| Secondary | ORR in All VAF Population, as Assessed by IRF | ORR was defined as the percentage of participants who experienced a BOR of CR or PR and was assessed using RECIST v1.1 by IRF. 95% CI was calculated by the exact binomial (Clopper-Pearson) method. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for all VAF participants. Data collection and analysis of ORR for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to approximately 28 months |
|
| ||||||||||||||||||||||||||
| Secondary | Duration of Response (DoR) in High VAF Population, as Assessed by IRF | DoR was defined as the time from the date of first response (CR or PR [whichever occurred first]) to the date of progression of disease or death of any cause, whichever occurred first, in participants with a confirmed CR or PR and was assessed using RECIST v1.1 by IRF. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for participants with high VAF and available data only. Data collection and analysis of DoR for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Median | 95% Confidence Interval | months | Up to approximately 28 months |
|
| ||||||||||||||||||||||||||
| Secondary | DoR in All VAF Population, as Assessed by IRF | DoR was defined as the time from the date of first response (CR or PR [whichever occurred first]) to the date of progression of disease or death of any cause, whichever occurred first, in participants with a confirmed CR or PR and was assessed using RECIST v1.1 by IRF. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for all VAF participants with available data. Data collection and analysis of DoR for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Median | 95% Confidence Interval | months | Up to approximately 28 months |
|
| ||||||||||||||||||||||||||
| Secondary | Progression Free Survival (PFS) in High VAF Population, as Assessed by IRF | PFS was defined as months from the first dose of the study drug to the first documented progressive disease (PD, appearance of one or more new lesions or at least a 20% increase in the sum of the diameters of target lesions) or death, whichever came first and was assessed using RECIST v1.1 by IRF. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for participants with high VAF and available data only. Data collection and analysis of PFS for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Median | 95% Confidence Interval | months | Up to approximately 28 months |
|
| ||||||||||||||||||||||||||
| Secondary | PFS in All VAF Population, as Assessed by IRF | PFS was defined as months from the first dose of the study drug to the first documented PD or death, whichever came first and was assessed using RECIST v1.1 by IRF. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for all VAF participants with available data. Data collection and analysis of PFS for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Median | 95% Confidence Interval | months | Up to 28 approximately months |
|
| ||||||||||||||||||||||||||
| Secondary | PFS Rate in High VAF Population, as Assessed by IRF | PFS rate was defined as the percentage of participants who had not experienced documented PD or death, whichever came first and was assessed using RECIST v1.1 by IRF at 6 and 9 month timepoints. Percentage of participants was calculated using the Kaplan-Meier method. 95% CI was calculated using normal approximation to the log transformed cumulative hazard rate | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for participants with high VAF and available data only. Data collection and analysis of PFS for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Number | 95% Confidence Interval | percentage of participants | 6 months and 9 months |
|
| ||||||||||||||||||||||||||
| Secondary | PFS Rate in All VAF Population, as Assessed by IRF | PFS rate was defined as the percentage of participants who had not experienced documented PD or death, whichever came first and was assessed using RECIST v1.1 by IRF at 6 and 9 month timepoints. Percentage of participants was calculated using the Kaplan-Meier method. 95% CI was calculated using normal approximation to the log transformed cumulative hazard rate. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for all VAF participants and available data. Data collection and analysis of PFS for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Number | 95% Confidence Interval | percentage of participants | 6 months and 9 months |
|
| ||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) in High VAF Population | OS was defined as months from first dose date until death from any cause. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for participants with high VAF only. Data collection and analysis of OS for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Median | 95% Confidence Interval | months | Up to approximately 28 months |
|
| ||||||||||||||||||||||||||
| Secondary | OS in All VAF Population | OS was defined as months from first dose date until death from any cause. Median was calculated using the Kaplan-Meier method. 95% CI was based on Brookmeyer and Crowley method with log-log transformation. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for all VAF participants. Data collection and analysis of OS for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Median | 95% Confidence Interval | months | Up to approximately 28 months |
|
| ||||||||||||||||||||||||||
| Secondary | OS Rate at 12 Months in High VAF Population | OS rate was defined as the percentage of participants who had not experienced or death and was assessed at 12 months. Percentage of participants was calculated using the Kaplan-Meier method. 95% CI was calculated using normal approximation to the log transformed cumulative hazard rate. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for participants with high VAF only. Data collection and analysis of OS for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 months |
|
| ||||||||||||||||||||||||||
| Secondary | OS Rate at 12 Months in All VAF Population | OS rate was defined as the percentage of participants who had not experienced or death and was assessed at 12 months. Percentage of participants was calculated using the Kaplan-Meier method. 95% CI was calculated using normal approximation to the log transformed cumulative hazard rate. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for all VAF participants. Data collection and analysis of OS for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 months |
|
| ||||||||||||||||||||||||||
| Secondary | Time to Response (TTR) in High VAF Population, as Assessed by IRF | TTR was defined as months from treatment start to first CR or PR (whichever was first recorded) in participants with confirmed CR or PR and was assessed using RECIST v1.1 by IRF. TTR was summarized descriptively by summary statistics. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for participants with high VAF and available data only. Data collection and analysis of TTR for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Median | Full Range | months | Up to approximately 28 months |
|
| ||||||||||||||||||||||||||
| Secondary | TTR in All VAF Population, as Assessed by IRF | TTR was defined as months from treatment start to first CR or PR (whichever was first recorded) in participants with confirmed CR or PR and was assessed using RECIST v1.1 by IRF. TTR was summarized descriptively by summary statistics. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for all VAF participants with available data. Data collection and analysis of TTR for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Median | Full Range | months | Up to approximately 28 months |
|
| ||||||||||||||||||||||||||
| Secondary | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | TEAEs were defined as adverse events (AEs) that started on or after the first dose of the study drug and within 30 days of the last administration of the study drug. Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was used for toxicity grading (Grade 3: severe or disabling; Grade 4: life-threatening; Grade 5: death related to AE). Clinically significant changes in laboratory tests, vital signs, and electrocardiogram results were reported as AEs. | SAS: consisted of all participants in the AIM-HN who received at least one dose of tipifarnib. Analysis was pre-specified for participants in the AIM-HN Cohort only. Data collection and analysis of safety for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Count of Participants | Participants | Up to approximately 28 months |
|
| |||||||||||||||||||||||||||
| Secondary | Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module 35 (EORTC QLQ-H&N35) Subscales | Change from Baseline score in pain, swallowing, speech problems, and senses problems subscales of EORTC QLQ-H&N35 are summarized individually. Raw scores for each subscale were linear transformations and standardized to range (0 - 100), with higher scores representing worse levels of symptoms. Change from Baseline was calculated as End of Treatment Observed - Baseline with a negative change representing a reduction in symptoms. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for participants in the AIM-HN Cohort with available data. Data collection and analysis of EORTC QLQ-H&N35 for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Median | Full Range | score on a scale | Baseline and End of Treatment Visit (up to approximately 28 months) |
|
| ||||||||||||||||||||||||||
| Secondary | Change From Baseline in the EuroQol-Visual Analog Scale (EQ-VAS) Score | The EQ-VAS forms part of the EQ-5D-5L and collects the self-rating health status from 0 (the worst imaginable health) to 100 (the best imaginable health). Change from Baseline was calculated as End of Treatment Observed - Baseline with a negative change representing an increase in symptoms. | mITT Analysis Set: consisted of all participants who received at least one dose of tipifarnib. Analysis was pre-specified for participants in the AIM-HN Cohort with available data. Data collection and analysis of EQ-VAS for participants in the Observational SEQ-HN Cohort was not pre-specified. | Posted | Median | Full Range | score on a scale | Baseline and End of Treatment Visit (up to approximately 28 months) |
|
|
Up to approximately 28 months
All-cause mortality - all enrolled participants. Serious AEs and other AEs - SAS: consisted of all participants in the AIM-HN who received at least one dose of tipifarnib. Analysis was pre-specified for participants in the AIM-HN Cohort only. Data collection and analysis of AEs for participants in the Observational SEQ-HN Cohort was not pre-specified.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tipifarnib Treatment Cohort: AIM-HN | Participants enrolled as part of AIM-HN received tipifarnib administered with food at a starting dose of 600 mg, orally, bid on Days 1-7 and 15-21 of 28-day cycles. | 41 | 59 | 28 | 59 | 56 | 59 |
| EG001 | Observational Cohort: SEQ-HN | Participants with HNSCC in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consented to provide first line outcome data and additional follow-up. | 149 | 237 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
| |
| Infected neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Sudden death | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Laryngeal stenosis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA (22.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Oesophageal stenosis | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Rectal prolapse | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Corona virus infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Pneumonia Escherichia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (22.0) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Corona virus infection | Infections and infestations | MedDRA (22.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (22.0) | Systematic Assessment |
|
There are agreements in place between clinical trial sites and the Sponsor (or its agents) that govern discussion or publication of trial results by the sites or their employees after the trial is completed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Operations | Kura Oncology, Inc. | 617-588-3755 | KO-TIP-007@kuraoncology.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 6, 2023 | Dec 15, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| D006258 | Head and Neck Neoplasms |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009371 | Neoplasms by Site |
Not provided
Not provided
| ID | Term |
|---|---|
| C402769 | tipifarnib |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|