Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations

The ORR of tipifarnib was response assessments according to RECIST 1.1. The estimate of the ORR was calculated based on the maximum likelihood estimator (i.e., crude percentage of subjects whose best overall response was complete response \[CR\] or partial response \[PR\]). The estimate of the ORR was accompanied by 2-sided 95% confidence interval (CI). The 95% CI was estimated using the Wilson score test-based method. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.

Time frame: Up to approximately 3 years

Population: The Full Analysis Set (FAS) Population excluding subjects for the following reasons: no baseline data; failure to receive at least 1 dose of tipifarnib; no post-baseline endpoint data subsequent to at least 1 dose of study drug.

An adverse event (AE) was any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started on or after the first dose of study drug and within 30 days of the last administration of study drug or immediately before the initiation of any other anticancer therapy. The Investigator was required to grade the severity/ intensity of each AE according to NCI-CTCAE version 4.03. If a severity/intensity of Grade 4 (life-threatening) or 5 (death) was applied to an AE, then the Investigator also reported the event as a serious AE.

Time frame: Up to approximately 3 years

Population: The ASaT Population consists of all enrolled subjects who received at least 1 dose of tipifarnib.

BOR according to RECIST 1.1. Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.

Time frame: Up to approximately 3 years

Population: The FAS Population excluding subjects for the following reasons: no baseline data; failure to receive at least 1 dose of tipifarnib; no post-baseline endpoint data subsequent to at least 1 dose of study drug.

DOR was the number of months from start date of PR or CR (whichever response was achieved first) to the first date that PD was documented (in subjects with an objective response). PD was determined by the Investigator using RECIST 1.1. The DOR was right-censored at the date for subjects who achieved CR or PR and met one of the following conditions: 1) when non-protocol anticancer treatment started before documentation of PD, 2) when death prior to documented PD or documented PD after more than 1 missed disease assessment visit, or 3) when alive and did not have documentation of PD before a data analysis cut-off date (therefore, analysis cut-off date was used as the censoring date). Median and 95% CI were calculated via Kaplan-Meier analysis.

Time frame: Up to approximately 3 years

Population: The Per Protocol (PP) Population was a subset of the FAS population that excluded subjects due to major deviations from the protocol that may have substantially affected the results of the primary analysis. Only participants participants with response data were included.

An analysis of OS was conducted to estimate median OS time and corresponding 95% CI. OS was defined as the time from first dose (Cycle 1 Day 1) to the occurrence of death due to any cause. In subjects without a death date, the OS was censored on 1) the last date of survival status if alive, 2) a data analysis cut-off date for subjects with no survival status documentation, or 3) the date a subject withdrew consent or was lost to follow-up if there was no additional information. Median and 95% CI were calculated via Kaplan-Meier analysis.

Time frame: Up to approximately 4 years

Population: The FAS Population excluding subjects for the following reasons: no baseline data; failure to receive at least 1 dose of tipifarnib; no post-baseline endpoint data subsequent to at least 1 dose of study drug.

PFS was defined as the time from first dose (Cycle 1 Day 1) to either first observation of progressive disease (PD) or occurrence of death due to any cause within 126 days (approximately 2 time-intervals for tumour assessments) of either first administration of tipifarnib or the last tumour assessment. Observation of PD could have been by either documented radiographic progression (i.e., scan results) or documentation of symptomatic or clinical progression agreed upon and documented by investigators. In subjects without a progression date or with a death date more than 126 days after the first administration of study drugs or the last tumour assessment, the PFS time should have been censored on the date of last tumour assessment or date of first administration of study tipifarnib.

Time frame: Up to approximately 3 years

Population: The FAS Population excluding subjects for the following reasons: no baseline data; failure to receive at least 1 dose of tipifarnib; no post-baseline endpoint data subsequent to at least 1 dose of study drug.