Genome-Based Assessment of Niraparib (ZEJULA®) Efficacy in Advanced Solid TumorS With Homologous Recombination Deficiency

Objectives:

• Primary Objective

• Antitumor activity defined as objective response at ≥ 8 weeks or stable disease (SD) at ≥ 16 weeks from the time of enrollment.
• Secondary Objectives

• Overall Survival (OS)
• Progression-Free Survival (PFS)
• Objective Response Rate (ORR) by RECIST v1.1
• Duration of response (DOR)
• Quality of life (QOL) assessed by EORTC-QLQ-C30
• Adverse Event (AEs)
• Exploratory biomarker analyses

Inclusion criteria

• Patient who agreed to participate in the KOSMOS-II master observation study.
• 19 years of age or older on the day of signing informed consent.
• Has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor.
• Has either known or suspected deleterious mutations in at least 1 of the genes involved in HRR or centrally confirmed HRD based on whole-genome sequencing (WGS).
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Has measurable disease per RECIST v1.1 as assessed by the local site investigator.
• Female participants of reproductive potential must agree to use contraception during the treatment period and for at least 6 months after the last dose. Male participants must agree to use contraception during the treatment period and for 90 days plus 5 X half-life after last dose.
• Has adequate organ function.
• Willing to provide biopsies from the tumor at screening to the central laboratory

Exclusion criteria

• Any previous exposure to PARP inhibitor
• Any other active malignancy or diagnosis of another malignancy within 2 years before study enrollment
• Has leptomeningeal metastases.
• Active central nervous system (CNS) lesions.
• Were resistant to prior platinum therapy (cisplatin, carboplatin, or oxaliplatin either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor.
• Any cytotoxic chemotherapy from a previous treatment regimen within 14 days.
• Has received prior endocrine therapy as cancer treatment within 2 weeks prior to administration of study intervention.
• Has received palliative radiotherapy encompassing >20% of the bone marrow within 1 week of the first dose of study treatment.
• Has an active infection requiring systemic therapy.
• Has hypertension that cannot be adequately controlled with medication.
• Has active tuberculosis.
• Has active infection such as hepatitis B, hepatitis C
• Has a known history of Human Immunodeficiency Virus (HIV) infection.

• Impairment of gastrointestinal function or gastrointestinal disorders 16) Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through 6 months after the last dose of the Investigational product.

• Patients who do not consent to adequate contraception throughout the study period.

• Has a known hypersensitivity to the components of the investigational product or its analogs.

• Since this drug contains lactose, patients with genetic problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

• Since this drug contains Yellow No. 4 (Tartrazine), patients with a history of hypersensitivity or allergy to this ingredient.

• Medical, psychiatric, cognitive, or other conditions that may interfere with the ability of the subject to understand the subject information, provide the informed consent, follow the protocol process, or complete the clinical trial.

• The investigator judges that it is not appropriate to participate in this study for else reasons.