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TOPACIO/Keynote-162 (NCT02657889): A phase 1/2 study of niraparib + pembrolizumab in patients (pts) with advanced triple-negative breast cancer or recurrent ovarian cancer (ROC)—Results from ROC cohort.
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2018
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Roc CohortBreast OncologyImmunologyGynecologyPathologyRecurrent Ovarian CancerPharmacotherapyImmunotherapyOvarian CancerPhase 1/2OncologyObjective Response RateClinical TrialsRadiation OncologyNovel TherapyMolecular OncologyHealth SciencesPlatinum-resistant OcCancer TreatmentPharmacologyTherapeutic EfficacyImmune Checkpoint InhibitorBreast CancerPfi ≥6 MonthsMedicine
106 Background: Platinum-resistant OC (PROC) has few treatment options. Niraparib is an oral PARP inhibitor (PARPi) approved for maintenance treatment of ROC. Anti–programmed death (PD)–1 monotherapies (eg, pembrolizumab) have shown low level activity in ROC, and beyond BRCAmut, PARPi have shown minimal activity in PROC. Preclinical data demonstrate synergy with PARPi + anti-PD-1 combinations. Methods: Eligible pts must have experienced a response lasting ≥6 months to first-line platinum therapy and were considered to have PROC per investigator’s assessment (eg, pts not eligible for further platinum) and no more than 5 prior treatment lines. While primary platinum-refractory (PRef) disease was excluded, secondary PRef disease was not. A phase 1 study previously established RP2D of niraparib 200 mg orally once daily + pembrolizumab 200 mg IV every 21 days. Primary and secondary endpoints included objective response rate (ORR = CR+PR) and disease control rate (DCR = CR+PR+SD). Genetic biomarkers were assessed by Stand Up To Cancer (SU2C) Ovarian Cancer Dream Team. Results: As of Jan 2018, 60/62 pts were evaluable for response assessment (≥1 on-study scan). Median age was 60 years. Median prior lines of chemotherapy was 2 (range: 1-5). Based upon platinum-free interval (PFI) to last platinum treatment, 64% of pts had PROC (PFI < 6 months), 19% had PRef disease (PFI < 30 days), and 17% had platinum-sensitive (PSens; PFI ≥6 months) disease. Twenty pts remain on treatment and 11 have received treatment for ≥6 months. Among the 60 evaluable pts, ORR/DCR were 25%/68%; among the 11 tumor BRCA (tBRCA) mut evaluable pts, ORR/DCR were 45%/73%. Responses were observed in 11/38 PROC pts, 2/11 PRef pts, and 1/10 PSens pts (platinum status unknown in 1 responder). Durability of response data will be presented. Follow-up is ongoing. The most common grade ≥3 TEAEs were anemia (19%) and thrombocytopenia (9%). Conclusions: With ORR of 25% in all PROC and ORR of 45% in tBRCAmut pts, niraparib + pembrolizumab appears promising. Additional evaluation of this combination in ROC is warranted. No new safety signals were identified with the combination. Clinical trial information: NCT02657889.