HNSCC, HRAS Gene Mutation
Conditions
Keywords
TIPIFARNIB, HEAD AND NECK CANCER
Brief summary
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.
Detailed description
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.
Interventions
DRUGTipifarnib
Tablet for oral administration
DEVICEHRAS Detection Assay
In Vitro Assay to detect HRAS mutations
Sponsors
Kura Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 without chemotherapy). 3. Documented treatment failure from most recent prior therapy (e.g. tumor progression, clinical deterioration, or recurrence), and from at least one prior platinum-containing regimen, in any treatment setting. 4. Known tumor missense HRAS mutation. 5. Measurable disease by RECIST v1.1. 6. ECOG performance status of 0-1. 7. Acceptable liver, renal and hematological function 8. Other protocol defined inclusion criteria may apply.
Exclusion criteria
1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma). 2. Received treatment for unstable angina within prior year, myocardial infarction within the prior year, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation. 3. Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1. 4. Active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy. Known history of infection with human immunodeficiency virus or an active infection with hepatitis B or hepatitis C. 5. Received treatment for non-cancer related liver disease within prior year. 6. Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF) | Up to approximately 28 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) in High VAF Population, as Assessed by IRF | Up to approximately 28 months | 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. |
| DoR in All VAF Population, as Assessed by IRF | Up to approximately 28 months | 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. |
| Progression Free Survival (PFS) in High VAF Population, as Assessed by IRF | Up to approximately 28 months | 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. |
| PFS in All VAF Population, as Assessed by IRF | Up to 28 approximately months | 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. |
| PFS Rate in High VAF Population, as Assessed by IRF | 6 months and 9 months | 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 |
| PFS Rate in All VAF Population, as Assessed by IRF | 6 months and 9 months | 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. |
| Overall Survival (OS) in High VAF Population | Up to approximately 28 months | 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. |
| ORR in All VAF Population, as Assessed by IRF | Up to approximately 28 months | 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. |
| OS Rate at 12 Months in High VAF Population | 12 months | 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. |
| OS Rate at 12 Months in All VAF Population | 12 months | 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. |
| Time to Response (TTR) in High VAF Population, as Assessed by IRF | Up to approximately 28 months | 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. |
| TTR in All VAF Population, as Assessed by IRF | Up to approximately 28 months | 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. |
| Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Up to approximately 28 months | 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. |
| 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 | Baseline and End of Treatment Visit (up to approximately 28 months) | 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. |
| Change From Baseline in the EuroQol-Visual Analog Scale (EQ-VAS) Score | Baseline and End of Treatment Visit (up to approximately 28 months) | 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. |
| OS in All VAF Population | Up to approximately 28 months | 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. |
Countries
Australia, Austria, Belgium, Denmark, Germany, Greece, Italy, Malaysia, Netherlands, Norway, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 59 |
| 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. | 237 |
| Total | 296 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 40 | 149 |
| Overall Study | Lost to Follow-up | 2 | 18 |
| Overall Study | Miscellaneous | 12 | 56 |
| Overall Study | Unwilling or unable to comply with study requirements | 0 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 10 |
Baseline characteristics
| Characteristic | Total | Observational Cohort: SEQ-HN | Tipifarnib Treatment Cohort: AIM-HN |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 121 Participants | 93 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 175 Participants | 144 Participants | 31 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 60 Participants | 37 Participants | 23 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 10 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 8 Participants | 8 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 272 Participants | 217 Participants | 55 Participants |
| Race/Ethnicity, Customized Not Reported | 12 Participants | 9 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 9 Participants | 7 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 4 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 213 Participants | 180 Participants | 33 Participants |
| Sex: Female, Male Female | 74 Participants | 59 Participants | 15 Participants |
| Sex: Female, Male Male | 222 Participants | 178 Participants | 44 Participants |
| Variant Allele Frequency (VAF) Status Participants with high VAF (>=20%) | 50 Participants | — | 50 Participants |
| Variant Allele Frequency (VAF) Status Participants with low VAF (< 20%) | 9 Participants | — | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 41 / 59 | 149 / 237 |
| other Total, other adverse events | 56 / 59 | 0 / 0 |
| serious Total, serious adverse events | 28 / 59 | 0 / 0 |
Outcome results
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.
Time frame: Up to approximately 28 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF) | 20.0 percentage of participants |
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.
Time frame: Baseline and End of Treatment Visit (up to approximately 28 months)
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | 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 | Pain | 0.0 score on a scale |
| Tipifarnib Treatment Cohort: AIM-HN | 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 | Swallowing | 8.3 score on a scale |
| Tipifarnib Treatment Cohort: AIM-HN | 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 | Senses problems | 0.0 score on a scale |
| Tipifarnib Treatment Cohort: AIM-HN | 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 | Speech problems | 0.0 score on a scale |
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.
Time frame: Baseline and End of Treatment Visit (up to approximately 28 months)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | Change From Baseline in the EuroQol-Visual Analog Scale (EQ-VAS) Score | 3.5 score on a scale |
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.
Time frame: Up to approximately 28 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | DoR in All VAF Population, as Assessed by IRF | 6.51 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.
Time frame: Up to approximately 28 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | Duration of Response (DoR) in High VAF Population, as Assessed by IRF | 6.51 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.
Time frame: Up to approximately 28 months
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any TEAEs | 58 Participants |
| Tipifarnib Treatment Cohort: AIM-HN | Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) | Any Grade 3 or Higher TEAEs | 43 Participants |
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.
Time frame: Up to approximately 28 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | ORR in All VAF Population, as Assessed by IRF | 18.6 percentage of participants |
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.
Time frame: Up to approximately 28 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | OS in All VAF Population | 6.21 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.
Time frame: 12 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | OS Rate at 12 Months in All VAF Population | 30 percentage of participants |
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.
Time frame: 12 months
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | OS Rate at 12 Months in High VAF Population | 31 percentage of participants |
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.
Time frame: Up to approximately 28 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | Overall Survival (OS) in High VAF Population | 6.97 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.
Time frame: Up to 28 approximately months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | PFS in All VAF Population, as Assessed by IRF | 2.23 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.
Time frame: 6 months and 9 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | PFS Rate in All VAF Population, as Assessed by IRF | 6 months | 26 percentage of participants |
| Tipifarnib Treatment Cohort: AIM-HN | PFS Rate in All VAF Population, as Assessed by IRF | 9 months | 18 percentage of participants |
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
Time frame: 6 months and 9 months
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | PFS Rate in High VAF Population, as Assessed by IRF | 6 months | 29 percentage of participants |
| Tipifarnib Treatment Cohort: AIM-HN | PFS Rate in High VAF Population, as Assessed by IRF | 9 months | 20 percentage of participants |
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.
Time frame: Up to approximately 28 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | Progression Free Survival (PFS) in High VAF Population, as Assessed by IRF | 2.60 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.
Time frame: Up to approximately 28 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | Time to Response (TTR) in High VAF Population, as Assessed by IRF | 1.9 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.
Time frame: Up to approximately 28 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tipifarnib Treatment Cohort: AIM-HN | TTR in All VAF Population, as Assessed by IRF | 1.9 months |