Assessed safety and tolerability of the combination administration of RAD001 and imatinib when given to patients with imatinib-refractory gastro-intestinal stromal tumors (GIST) by number of participants with adverse events.

Safety Population: All patients (except for the 3 patients who did not meet the protocol inclusion/exclusion criteria) were included in the Safety population for Phase I. All patients were included in the Safety population for Phase II.

Assessed clinical efficacy of the combination regimen in this patient population per BOR by Overall response (CR + PR). Complete response: Disappearance of all target lesions; Partial response: ≥ 30% decrease in the sum of the longest diameter of target lesions compared to baseline (and not ≥20% increase compared to smallest sum).

Intent-to-treat (ITT) population: All patients (except for the 3 patients who did not meet the protocol inclusion/exclusion criteria) were included in the ITT population.

Assessed the pharmacokinetics (PK) of the combination administration of RAD001 and imatinib in this patient population.

Pharmacokinetics (PK) population: The PK population included 18% of Stratum I patients and 47% of Stratum II patients

Assessed clinical efficacy of the combination regimen in this patient population per Overall Survival (OS). Overall survival was defined as the time from date of start of treatment to date of death due to any cause. For patients still receiving study medication at the time of the analysis, survival was censored at the date of last examination. If a patient was not known to have died but was no longer continuing with study medication, survival was censored at the date of last contact.

ITT population: All patients (except for the 3 patients who did not meet the protocol inclusion/exclusion criteria) were included in the ITT population for phase I. All patients were included in the ITT population for phase II.

assess mTOR pathway activity before treatment, and inhibition of mTOR pathway activity during treatment as a predictive factor of response, as shown by molecular pathological examination of the tumor.

Pharmacodynamic population: Molecular pathology and pharmacogenomic assessments were planned, but not carried out due to an alternative therapy that became available after the initiation of this study.

assess the relationship between drug-induced changes in the principal molecular marker of intratumoral mTOR activity and changes in other molecular markers of tumoral activity (e.g. indicators of pathway activity, cell proliferation and apoptosis).

Pharmacodynamic population: Molecular pathology and pharmacogenomic assessments were planned, but not carried out due to an alternative therapy that became available after the initiation of this study.

assess the relationship between drug-induced changes in tumoral metabolism, as shown by functional imaging with 18F-fluorodeoxyglucose positron emission tomography (FDC-PET), with clinical outcome and changes in molecular pathology.

PET scans at baseline and as follow-up were planned to assess functional changes in tumors for patients on treatment. This analysis was not carried out due to alternative therapy that became available after the initiation of this study.

Assessed clinical efficacy of the combination regimen in this patient population per Progression-free survival (PFS). Progression-free survival (PFS) was the time from date of start of treatment to the date of first documented progression or death due to any cause. Per protocol (PP) population includes patients with no known overall lesion response during 4 months +/- 2 weeks, or who later had response of CR/PR/stable disease (SD). PP population excludes patients with no known response during 4 months + / -2 weeks and no subsequent CR/PR/SD.

Per Protocol population: The per-protocol population included 82% of Stratum I patients and 75% of Stratum II patients.

Assessed clinical efficacy of the combination regimen in this patient population per Progression-free survival (PFS). Progression-free survival (PFS) was the time from date of start of treatment to the date of first documented progression or death due to any cause. If a patient had not progressed or died, progression-free survival was censored at the time of last adequate tumor assessment.

According to the study protocol no tumor assessments were performed after discontinuation of treatment with study drug. Therefore, for all patients who discontinued treatment without a documented progression but died thereafter, death was considered as PFS event only if it occurred within the regular safety follow-up of 28 days after discontinuation. Otherwise, the PFS time was censored at the last adequate tumor assessment.

ITT population: All patients were included in the ITT population for Phase II.

On treatment deaths were collected from FPFT up to 28 days after study drug discontinuation, for a maximum duration of 35.52 months (treatment duration ranged from 0.36 to to 35.52 months for the phase I part) and a maximum duration of 21.88 months (treatment duration of 0.16 to 21.88 months for the phase II part). Deaths post treatment survival follow up were collected after the on treatment period, up to 70 months.

ITT population: All patients (except for the 3 patients who did not meet the protocol inclusion/exclusion criteria) were included in the ITT population for phase I. All patients were included in the ITT population for phase II.