Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Niraparib 100mg Oral Capsule
Niraparib · 5 trials · 3 indications
As per BICR, rPFS is time interval from the date of randomization to radiographic progression or death, whichever occurred first. Radiographic progression was determined by: (1) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per response evaluation criteria in solid tumors (RECIST) 1.1; (2) Progression of bone lesions observed by bone scan based on prostate cancer working group 3 (PCWG3) criteria. PCWG3 criteria: bone progression was confirmed by subsequent scan greater than or equal to (\>=) 6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. Confirmatory scan \>=2 new lesions indicate progression; scan does not show \>=2 new lesions means no progression. If Week 8 scan less than (\<) 2 new bone lesions compared to baseline, the initial scan \>=2 new lesions compared to Week 8 scan indicates progression if confirmed by subsequent scan \>=6 weeks later.
As per BICR, rPFS is time interval from the date of randomization to radiographic progression or death, whichever occurred first. Radiographic progression was determined by: (1) progression of soft tissue lesions measured by CT or MRI as per RECIST 1.1; (2) Progression of bone lesions observed by bone scan based on PCWG3 criteria. PCWG3 criteria: bone progression was confirmed by subsequent scan \>=6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. Confirmatory scan \>=2 new lesions indicate progression; scan does not show \>=2 new lesions means no progression. If Week 8 scan \<2 new bone lesions compared to baseline, the initial scan \>=2 new lesions compared to Week 8 scan indicates progression if confirmed by subsequent scan \>=6 weeks later.
Number of participants with specified toxicity during Cycle 1 was reported. Only toxicities that occurred during safety evaluation period(defined as first 28 days of treatment-Cycle 1 of Part 1) was used for analysis of specified toxicities and for dose reduction decisions. Toxicities were graded for severity as per NCI-CTCAE, version 4.03. Safety evaluation criteria were: Any Grade(G) \>=3 non-hematological toxicity without anorexia, or constipation, fatigue improved to G\<=2 in \<7 days, vomiting and diarrhea resolved in \<=3 days, laboratory abnormalities with hospitalization, tumor flare improved to G\<=2 in \<=7 days, elevation in AST/ALT for \<=7 days and G3 hypertension controlled by medical therapy; any treatment-related(TR)G4 or G\>=3 thrombocytopenia required platelet transfusion; Any TR G4 neutropenia \>=7 days or G3 or 4 neutropenia with infection/fever \>38.5 degrees Celsius; Any TR SAE or intolerable toxicity.
ORR of soft tissue (visceral or nodal disease) was defined as percentage of participants with measurable disease who achieved a best response of either complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with no evidence of bone progression according to prostate cancer working group 3 (PCWG3) criteria.
Composite response rate was defined as the percentage of participants who had a composite response which is defined as one of the following PCWG3 criteria: Objective response (percentage of participants with measurable disease who achieved a best response of either CR or PR as assessed by RECIST 1.1 with no evidence of bone progression according to PCWG3 criteria) (confirmed per RECIST 1.1), or; circulating tumor cells (CTC) response: defined as CTC=0 per 7.5 milliliters (mL) of blood at 8 weeks for participants who had CTC greater than or equal to (\>=) 1 at baseline or CTC less than (\<) 5 per 7.5 mL with CTC \>=5 at baseline, confirmed by a second consecutive value obtained 4 or more weeks later, or prostate-specific antigen (PSA) declined of \>=50 percentage (%), measured twice 3 to 4 weeks apart. This outcome measure was analyzed for specified arms only as pre-planned in the protocol.
AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment.
AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment.
AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade was made using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) as Grade 1 (mild): awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 (moderate): sufficient discomfort is present to cause interference with normal activity; Grade 3 (severe): extreme distress, causing significant impairment of functioning or incapacitation, prevents normal everyday activities; Grade 4 (Life-threatening): urgent intervention indicated; and Grade 5 (death).
AE was defined as an any untoward medical occurrence in a clinical study subject administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An assessment of severity grade was made using the NCI-CTCAE as Grade 1 (mild): awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 (moderate): sufficient discomfort is present to cause interference with normal activity; Grade 3 (severe): extreme distress, causing significant impairment of functioning or incapacitation, prevents normal everyday activities; Grade 4 (Life-threatening): urgent intervention indicated; and Grade 5 (death).
Cmax is defined as maximum observed plasma concentration of niraparib and abiraterone acetate (AA) after a single dose.
Cmax/dose of niraparib was defined as maximum observed plasma concentration of niraparib Cmax normalized by the dose of niraparib administered with AA after a single dose.
AUC(0-168 hours) was defined as area under the plasma concentration-time curve from time zero to 168 hours of Niraparib administered with AA After a single dose.
AUC0(168 hours)/dose was defined as area under the plasma concentration-time curve for niraparib from time 0 to 168 hours of niraparib administered with AA after a single dose.
ORR defined as percentage of participants with BRCA DNA-repair anomalies and measurable disease whose best response is either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and with no evidence of bone progression per Prostate Cancer Working Group 3 (PCWG3) criteria.
Cmax,ss is defined as maximum observed analyte concentration at steady state.
AUC (0-24h),ss is defined as area under the plasma concentration-time curve from time zero to 24 hours at steady state.
Ratio of individual Cmax,ss values between test and reference treatment will be assessed.
Ratio of individual AUC (0-24h),ss values between test and reference treatment will be assessed.
RP2D will be defined as the highest dose of study drug at which less than 33 percent (%) of participants experience dose limiting toxicity (DLT).
Number of participants will be assessed to further explore safety and antitumor activity in Part 2 (dose expansion) of study.
| Arm | Type | Description |
|---|---|---|
| Cohort 1: Participants with mCRPC and HRR Gene Alteration | EXPERIMENTAL | Participants with L1 metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alteration will receive combination of niraparib 200 milligrams (mg) or matching placebo and abiraterone acetate (AA) 1000 mg plus prednisone 10 mg. In the open label extension (OLE) phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg. |
| Cohort 2: Participants with mCRPC and No HRR Gene Alteration | EXPERIMENTAL | Participants with L1 mCRPC and no HRR Gene alteration will receive combination of niraparib 200 mg or matching placebo and AA 1000 mg plus prednisone 10 mg. In the OLE phase participants earlier receiving the combination of niraparib and AAP may continue to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg and those receiving placebo and AAP may cross over depending on the outcome of study to receive open-label combination of niraparib 200 mg and AA 1000 mg plus prednisone 10 mg. |
| Cohort 3 (Open-label): Participants with mCRPC | EXPERIMENTAL | Participants with mCRPC will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets plus prednisone 10 mg. |
| Combination 1:Dose Selection: Niraparib + cetrelimab (Part 1) | EXPERIMENTAL | Dose regimen 1: The participants will receive niraparib 200 milligram (mg) orally once daily in combination with cetrelimab 240 mg intravenously (IV) once every 2 weeks. Dose regimen 2: The participants will receive niraparib 200 mg orally once daily in combination with cetrelimab 480 mg IV once every 4 weeks in 28-day treatment cycles until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. The safety evaluation team (SET) will determine if an additional cohort is necessary, based on the data from dose regimens 1 and 2. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study. |
| Combination 1:Dose Expansion: Niraparib + cetrelimab (Part 2) | EXPERIMENTAL | Participants will be assigned to either Cohort 1A (Biomarker \[BM\] positive \[+\]) or Cohort 1B (BM negative \[-\]) and will receive established RP2D of cetrelimab and niraparib, in Part 2 until disease progression, unacceptable toxicity, death, or the sponsor terminates the study. A futility analysis will be performed for the Cohort 1B after 10 BM- participants are enrolled in Part 2. This cohort will be closed if the response is less than predetermined response rate as outlined in the protocol. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study. |
| Combination 2: Dose Expansion: Niraparib + AA-P (Part 2) | EXPERIMENTAL | Participants will be assigned to one of 4 cohorts based on biomarker status - Cohort 2A (BRCA biallelic loss), 2B (other DRD biallelic loss), 2C (BRCA monoallelic loss), or 2D (other DRD monoallelic loss), and will receive niraparib 200 mg once daily in combination with abiraterone acetate 1000 mg (4\*250 mg) plus 10 mg prednisone (5 mg twice daily) throughout treatment phase. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study. |
| Combination 3: Niraparib + AA-P | EXPERIMENTAL | Participants will be assigned to one of three cohorts to receive AA-P with or without niraparib. Participants in the Treatment Phase of this combination will be offered the option to enter the Long-term Extension Phase of the study. |
| Niraparib | EXPERIMENTAL | Participants will receive 300 milligram (mg) niraparib (3 capsules\*100 mg) orally once daily. |
| Treatment Sequence ABD | EXPERIMENTAL | Participants will receive single doses of niraparib and abiraterone acetate (AA) using niraparib Formulation 1 as Treatment A in Treatment Period 1, followed by multiple doses of niraparib and AA using niraparib Formulation 2 as Treatment B in Treatment Period 2, followed by multiple doses of niraparib and AA using niraparib Formulation 4 as Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AA-prednisone (AAP) or AAP alone. |
| Treatment Sequence ADB | EXPERIMENTAL | Participants will receive Treatment A in Treatment Period 1 followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. |
| Treatment Sequence CBD | EXPERIMENTAL | Participants will receive single doses of niraparib and AA using niraparib Formulation 3 as Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment D in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. |
| Treatment Sequence CDB | EXPERIMENTAL | Participants will receive Treatment C in Treatment Period 1, followed by Treatment D in Treatment Period 2, followed by Treatment B in Treatment Period 3. From Period 2 onwards and during Extension and Long-term Extension Phases, all participants will continue to receive treatment with niraparib and AAP or AAP alone. |
| Niraparib + Apalutamide/[Abiraterone Acetate + Prednisone] | EXPERIMENTAL | Participants will receive initial starting dose of Niraparib 200 milligram (mg) once daily in combination either with Apalutamide 240 mg (4\*60 mg) once daily or Abiraterone Acetate 1000 mg (4\*250 mg) plus 10 mg Prednisone (5 mg twice daily) for 28 days of cycle 1. Once a safe dose of niraparib is selected with each Andrgen Receptor (AR)-targeted therapy \[Apalutamide or Abiraterone Acetate plus Prednisone\], then an expansion phase (Part 2) will open to further explore safety and assess antitumor activity. |
| Name | Type | Description |
|---|---|---|
| Niraparib | DRUG | Participants will receive niraparib 200 mg capsules or tablets once daily. |
| Abiraterone Acetate | DRUG | Participants will receive AA 1000 mg tablets once daily. |
| Prednisone | DRUG | Participants will receive prednisone 10 mg tablets daily. |
| Placebo | DRUG | Participants will receive matching placebo once daily. |
| New Formulation of Niraparib and Abiraterone Acetate (AA) | DRUG | Participants will receive a new formulation of niraparib 200 mg and AA 1000 mg tablets once daily. |
| Niraparib 200 mg | DRUG | Participants will receive niraparib 200 mg orally. |
| Cetrelimab 240 mg | DRUG | Participants will receive cetrelimab 240 mg IV every 2 weeks. |
| Cetrelimab 480 mg | DRUG | Participants will receive cetrelimab 480 mg IV every 4 weeks. |
| Abiraterone acetate 1000 mg | DRUG | Participants will receive AA 1000 mg orally. |
| Prednisone 5 mg | DRUG | Participants will receive prednisone 5 mg orally. |
| Abiraterone Acetate (AA) | DRUG | Abiraterone Acetate will be administered orally. |
| Apalutamide | DRUG | Participants will receive apalutamide 240 mg (4\*60 mg) once daily orally. |
Inclusion Criteria: * HRR gene alteration (as identified by the sponsor's required assays) as follows: 1. Cohort 1: positive for HRR gene alteration 2. Cohort 2: not positive for DRD (that is, HRR gene alteration) 3. Cohort 3: eligible by HRR status * Metastatic disease documented by positiv...
Niraparib is an investigational small molecule PARP inhibitor being studied for the treatment of prostate cancer, specifically metastatic castration-resistant prostate cancer. It is being evaluated in combination with abiraterone acetate and prednisone in a Phase 3 clinical trial for men with metastatic prostate cancer.
Niraparib targets PARP, which stands for poly ADP-ribose polymerase, a class of enzymes involved in DNA repair. By inhibiting PARP, niraparib is designed to interfere with the ability of cancer cells to repair DNA damage, potentially leading to cancer cell death.
Niraparib is being developed by Johnson & Johnson, which trades under the ticker symbol JNJ on the stock exchange. The company is conducting clinical trials to evaluate niraparib for the treatment of prostate cancer.
Niraparib is in Phase 3 clinical development for prostate cancer. The Phase 3 trial, NCT03748641, is studying niraparib in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone alone in men with metastatic prostate cancer.
Niraparib is being studied in several clinical trials for prostate cancer, including NCT03748641, a Phase 3 trial with 765 participants, and NCT03431350, a Phase 2 trial with 136 participants. These trials are evaluating niraparib alone or in combination with other therapies.
Yes, Niraparib 200 mg and Niraparib 100mg Oral Capsule are dosage forms of the same drug, niraparib. Additionally, Niraparib+ Abiraterone acetate fixed dose combination (FDC) refers to a combination product containing niraparib and abiraterone acetate.