A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II)

The number of Part 1 (Phase 1) patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.

Time frame: Cycle 1 Day 1 to Cycle 1 Day 21

Population: DLT-evaluable population - all patients enrolled into Part 1 of the study who received at least 17 complete days of rucaparib and completed Cycle 1 of treatment, or who experienced a DLT in Cycle 1.

The confirmed response rate by RECIST v1.1 is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) on subsequent tumor assessment at least 28 days after first response documentation.

Time frame: Time from first dose to date of progression, up to approximately 8 months

Population: Efficacy-Evaluable Population - all Part 2 patients who met eligibility criteria, received at least 1 dose of rucaparib, had measurable tumor lesions at baseline, and had at least 1 post-baseline disease assessment. 2 patients in Part 2A discontinued treatment due to an AE and did not have a post-baseline disease assessment.

AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation

Time frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

Population: PK-evaluable population - all patients enrolled into Part 1 of the study who received at least one dose of rucaparib and had adequate PK assessments drawn for determination of the PK profile. For some arms, the number analyzed at Day 1 and Day 15 differs from the overall number based on number of evaluable samples collected at each time point.

Cmax = maximum concentration following administration of rucaparib

Time frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

Population: PK-evaluable population - all patients enrolled into Part 1 of the study who received at least one dose of rucaparib and had adequate PK assessments drawn for determination of the PK profile. For some arms, the number analyzed at Day 1 and Day 15 differs from the overall number based on number of evaluable samples collected at each time point.

Tmax = time to maximum concentration following administration of rucaparib

Time frame: Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

Population: PK-evaluable population - all patients enrolled into Part 1 of the study who received at least one dose of rucaparib and had adequate PK assessments drawn for determination of the PK profile. For some arms, the number analyzed at Day 1 and Day 15 differs from the overall number based on number of evaluable samples collected at each time point.

Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of PD per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan.

Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 48 months

Population: Safety population - all Part 2 patients with confirmed response per investigator.

AUC last = Area under the plasma concentration-time curve from time 0 to the last recorded observation. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted AUC last values were calculated for each arm.

Time frame: Day -7 to Cycle 1 Day 1, or approximately 7 days

Population: A subset of patients treated with either 40 mg, 300 mg, or 600 mg rucaparib. For the 40 mg and 300 mg arms, the number analyzed at Day 1 and Day 15 differs from the overall number based on number of evaluable samples collected at each time point.

Cmax = maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Cmax values were calculated for each arm.

Time frame: Day -7 to Cycle 1 Day 1, or approximately 7 days

Population: A subset of patients treated with either 40 mg, 300 mg, or 600 mg rucaparib

Tmax = time to maximum concentration following administration of rucaparib. The effect of food on rucaparib PK parameters was assessed over a 24-hour period in blood samples from a subset of patients. Patients were given a single dose of 40 mg or 300 mg rucaparib (Part 1), or 600 mg rucaparib (Part 3) and were randomized to one of two sequences where they were either Fed (with a high-fat meal) or Fasted (without a high-fat meal) on Day -7 or Cycle 1 Day 1. On each day, patients underwent blood sampling for PK at the specified time points. The median Fed and Fasted Tmax values were calculated for each arm.

Time frame: Day -7 to Cycle 1 Day 1, or approximately 7 days

Population: A subset of patients treated with either 40 mg, 300 mg, or 600 mg rucaparib

Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death, due to any cause. Patients without a documented event of death will be censored on the date of their last visit.

Time frame: Cycle 1 Day 1 to date of death, assessed up to 38 months

Population: Safety population: Consist of all Part 2B patients who received at least one dose of rucaparib

PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first.

Time frame: Cycle 1 Day 1 to End of Treatment, up to approximately 51 months

Population: Safety population: Consist of all Part 2 patients who received at least one dose of rucaparib

QTcF value change from baseline by daily dose corrected using Fridericia's method (QTcF). To evaluate the effects of rucaparib on the QT (interval from Q wave to T wave)/QTc (interval corrected for heart rate) interval, all patients underwent serial ECG monitoring at Screening, on Cycle 1 Day -1, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 22, on Day 1 of all subsequent cycles, at the EOT Visit, and as clinically indicated. Worst post-baseline QTcF value was used to categorize each patient.

Time frame: Screening to End of Treatment, up to approximately 15 months

Population: Safety population: Consist of all Part 1 patients who received at least one dose of rucaparib. One patient in the 40 mg dose group had no Baseline evaluation and was excluded from analyses of change from Baseline.