The main purpose of this study is to investigate the safety, tolerability, preliminary efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of biomarker-guided novel anticancer agent(s) as monotherapy or combination therapy for the treatment of participants with advanced/recurrent ovarian cancer. Substudy 1 will investigate the safety, tolerability, preliminary efficacy, PK and PD of saruparib monotherapy in participants with BReast CAncer gene (BRCA) mutated epithelial ovarian, fallopian tube, or primary peritoneal cancer.
This Phase I/II, open-label, multicentre study will employ a platform design utilising a Master Protocol with multiple parallel, open-label substudies. Substudy 1 is a single-arm, open label, Phase II multicentre study investigating the safety, tolerability, preliminary efficacy, PK, and PD of saruparib monotherapy, as neoadjuvant treatment in participants with newly diagnosed, tBRCA1/2m International Federation of Gynecology and Obstetrics (FIGO) 2014 Stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer, and who are eligible for neoadjuvant treatment with planned interval debulking surgery (IDS).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Participants will receive saruparib via oral administration.
Research Site
Barcelona, Spain
Number of participants with treatment-emergent adverse event (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to discontinuation
To assess the safety and tolerability of novel biomarker guided treatment in participants with advanced/recurrent ovarian cancer.
Time frame: From Day 1 to Survival Follow up (approximately 6 months)
Substudy 1: Estimate of objective response rate (ORR) defined as proportion of participants who have a complete or partial response
To estimate the efficacy of neoadjuvant treatment (and prior to IDS) with saruparib single-agent by assessment of ORR in participants with newly diagnosed tBRCA1/2m advanced epithelial ovarian cancer and with measurable disease at baseline.
Time frame: From Day 1 to IDS surgery (within 6 weeks after conclusion of study intervention treatment [Day 1 until 12 weeks])
Substudy 1: Estimate of confirmed cancer antigen 125 (CA125) response rate defined as at least 50% reduction in serum CA-125 levels from pre-treatment levels
To estimate the efficacy of neoadjuvant treatment (and prior to IDS) with saruparib single-agent in participants with newly diagnosed tBRCA1/2m advanced epithelial ovarian cancer and evaluable for CA125 response per the GCIG criteria.
Time frame: Screening (Day -28), Day 1 (Cycle 1) and Day 15 (Cycle 2) (28-day cycles), End of Treatment (7 days after final dose), Pre-surgery Follow up
Substudy 1: Proportion of participants with pathological complete response (pCR) defined as no macroscopic residual and no microscopic (viable) disease on histologic evaluation of all surgical specimens
To estimate the efficacy of neoadjuvant treatment with saruparib single-agent by assessment of pCR in participants with newly diagnosed tBRCA1/2m advanced epithelial ovarian cancer and with measurable disease at baseline.
Time frame: IDS Follow up period (IDS surgery within 6 weeks after conclusion of study intervention treatment [Day 1 until 12 weeks])
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Substudy 1: Proportion of participants with complete surgical resection of tumour at IDS defined as no macroscopic tumour remains after surgery
To estimate the efficacy of neoadjuvant treatment with saruparib single-agent by assessment of CRR in participants with newly diagnosed tBRCA1/2m advanced epithelial ovarian cancer and with measurable disease at baseline.
Time frame: IDS Follow up period (IDS surgery within 6 weeks after conclusion of study intervention treatment [Day 1 until 12 weeks])
Substudy 1: Area under the plasma drug concentration-time curve (AUC)
To characterise the PK of saruparib and its metabolite(s) if applicable, as monotherapy in plasma following a single dose and at steady state after multiple dosing, when given orally as neoadjuvant monotherapy prior to IDS participants with newly diagnosed tBRCA1/2m advanced epithelial ovarian cancer.
Time frame: Day 1 (Cycle 1 and Cycle 3) (28-day cycles)
Substudy 1: Maximum plasma concentration of the drug (Cmax)
To characterise the PK of saruparib and its metabolite(s) if applicable, as monotherapy in plasma following a single dose and at steady state after multiple dosing, when given orally as neoadjuvant monotherapy prior to IDS participants with newly diagnosed tBRCA1/2m advanced epithelial ovarian cancer.
Time frame: Day 1 (Cycle 1 and Cycle 3) (28-day cycles)
Substudy 1: Time to maximum plasma concentration (tmax)
To characterise the PK of saruparib and its metabolite(s) if applicable, as monotherapy in plasma following a single dose and at steady state after multiple dosing, when given orally as neoadjuvant monotherapy prior to IDS participants with newly diagnosed tBRCA1/2m advanced epithelial ovarian cancer.
Time frame: Day 1 (Cycle 1 and Cycle 3) (28-day cycles)