Table 2

The summary of ongoing clinical trials with PARP inhibitors

AgentTrialPhaseDesignPrimary and secondary end pointResults
Niraparib (Zejula)TOPACIO/KEYNOTE-16236 I/IIPhase I: dose-escalation: ascending doses of niraparib up to 300 mg/day orally on days 1–21 and pembrolizumab 200 mg intravenously on day 1 of each 21-day cycle
Phase II: niraparib in combination with pembrolizumab 200 mg intravenously on day 1 of each 21-day cycle.
Phase I: number of subjects reporting dose-limiting toxicities
Phase II: ORR.
To date, ORR is 29% and DCR is 49%. Median PFS in BRCAmut group is 8.1 months. Treatment-related grade≥3 AEs occurred in 27 patients (50%); most common were thrombocytopenia (13%) and anemia (11%). Follow-up is ongoing.
BRAVO37 IIIControlled trial of niraparib versus physician’s choice monotherapy with eribulin, capecitabine, vinorelbine or gemcitabine.The primary end point was to assess PFS. Secondary end points included OS, PFS by local assessment (local-PFS), ORR and safety.After the preplanned interim analysis, recruitment was halted on the basis of futility, noting a high degree of discordance between local and central PFS assessment in the PC arm that resulted in informative censoring. At the final analysis (median follow-up, 19.9 months), median centrally assessed PFS was 4.1 vs 3.1 months.
RucaparibRUBY40 41 IIRucaparib 600 mg two times per day orally, 28-day cycle, number of cycles: until progression or unacceptable toxicity develops.Primary end point: clinical benefit rate in 3 years with either CR, PR or SD lasting for at least 16 weeks.
*Secondary end point: to assess the CR, PR, SD, PFS, OS and AEs in a 3-year time frame.
As of January 14, 2019, the median number of cycles was 2 (1–20), and 37/40 patients were evaluable for CBR. Five patients (13.5%) demonstrated clinical benefit, three PR and one SD>31 weeks. Nineteen patients had grade 3–4 toxicities. Three patients discontinued due to toxicity. Preliminary analyses showed that four patients presented high large-scale state transitions, and three presented a somatic biallelic loss of function in HR-related genes.
VeliparibBrighTNess47 48 IIIArm I: veliparib+carboplatin+paclitaxel followed by doxorubicin/cyclophosphamide (AC)
*Arm II: placebo+placebo+paclitaxel followed by AC.
*Arm B: placebo+carboplatin+paclitaxel followed by AC.
Primary end point: to assess the PCR in the breast tissue and the lymph node tissue on completion of pre-operative systemic therapy and definitive surgery.
Secondary end point: to assess PFS, OS, and the rate of eligibility for breast conservation after therapy.
As of September, 2021, those with a pathological CR had a 74% reduction in risk of an event compared with those with no pathological CR. After a median follow-up of 4.5 years, no significant differences have emerged in OS. Deaths have occurred in 12.0% of the paclitaxel/carboplatin/veliparib arm, 10.0% of the paclitaxel/carboplatin arm and 13.9% of the paclitaxel arm.
BROCADE-3111 IIIVeliparib placebo with carboplatin and paclitaxelPrimary end point: to assess PFS from the date the subject is randomized to the date the subject experiences a confirmed event of disease progression or to the date of death if disease progression is not reached to the date of death if disease progression is not reached.
Secondary end point: to assess OS, CBR, ORR, and PFS2 measured up to 5 years after the last subject enrolled.
The median PFS was 14.5 months in the veliparib group vs 12.6 months in the control group. Serious AEs occurred in 115 (34%) patients in the veliparib group vs 49 (29%) patients in the control group. There were no study drug-related deaths.
BROCADE46 IIVeliparib in combination with TMZ or in combination with carboplatin/paclitaxel compared with placebo plus carboplatin/paclitaxel (PCP).Primary end point: to determine whether veliparib in combination with TMZ or in combination with carboplatin/paclitaxel improves PFS compared with placebo plus carboplatin/paclitaxel.
Secondary end point: to assess OS, CBR, ORR, and CIPN in patients treated with veliparib plus carboplatin/paclitaxel, versus placebo plus carboplatin/paclitaxel.
The tertiary end point: to assess ECOG performance status, quality of life and exploratory correlative end points.
For eliparib with carboplatin/paclitaxel versus placebo plus carboplatin/paclitaxel, median PFS was 14.1 and 12.3 months, respectively, interim median OS 28.3 and 25.9 months and ORR 77.8% and 61.3%. For TMZ versus placebo group, median PFS was 7.4 months, interim median OS 19.1 months, and ORR 28.6%. AEs (all grades) of neutropenia, anemia, alopecia, and neuropathy were less frequent with TMZ versus PCP.
  • AEs, adverse events; CBR, clinical benefit rate; CIPN, chemotherapy-induced peripheral neuropathy; CR, complete response; DCR, disease control rate; ECOG, Eastern Cooperative Oncology Group; ORR, objective response rate; OS, overall survival; PC, Physician's choice chemotherapy; PCR, pathological complete response; PFS, progression-free survival; PR, partial response; SD, stable disease; TMZ, temozolomide.