An open-label, multi-center, single-arm, phase 2 study of fluzoparib in patients with germline BRCA1/2 mutation and platinum-sensitive recurrent ovarian cancer

6012 Background: We previously reported significantly improved progression-free survival (PFS) with the chemotherapy-free regimen of niraparib and bevacizumab compared to niraparib alone, in women with platinum-sensitive relapsed ovarian cancer (PSROC), regardless of homologous recombination deficiency (HRD) status (MyChoice HRD), duration of chemotherapy-free interval (CFI) and number of previous lines of therapy (Mirza MR et al, Lancet Oncol 2019). We now present the updated PFS, overall survival (OS) and other efficacy and safety endpoints. Methods: In this randomized, open-label, phase 2 study, women with measurable/evaluable, high-grade serous or endometrioid PSROC were randomized to niraparib 300mg once daily or the combination of niraparib 300mg once daily and bevacizumab 15mg/kg IV every 3 weeks until disease progression (1:1 randomization). The primary endpoint was PFS. Stratification was according to HRD status and CFI (6-12months (mo) vs. > 12mo). First-line maintenance bevacizumab was permitted. Results: Of 97 enrolled patients, 48 were randomized to niraparib monotherapy and 49 to the chemotherapy-free combination. The combined treatment significantly improved PFS compared to niraparib alone: updated median PFS 12.5 mo vs. 5.5 mo; hazard ratio (HR) adjusted for stratification factors 0.34; 95% confidence interval (CI) [0.21 to 0.55]; P < 0.0001. Preplanned exploratory subgroup analyses: patients with HRD-positive tumors (n = 54) HR 0.41 (CI, 0.23-0.76); HRD-negative disease (n = 43) HR, 0.40 (CI, 0.20-0.79); Time to First Subsequent Therapy (TFST) (n=97) HR, 0.4 (CI, 0.25-0.64); PFS2 (n=97) HR 0.55 (CI, 0.35-0.88); Time to Second Subsequent Therapy (TSST) (n=97) HR, 0.56 (CI, 0.35-0.90); OS (49 events only) HR, 0.77 (CI, 0.42-1.41). There was no difference in treatment-emergent grade 3-4 adverse events except for the rate of hypertension (22.9% vs. 0%) and neutropenia (8.3% vs. 2.0%). Patient-reported outcomes measured using EORTC QLQ-C30 and OV28 were similar for both treatment arms. Conclusions: Updated PFS consistently demonstrates that the niraparib-bevacizumab combination had clinically and statistically meaningful activity in PSROC. This phase 2 study was not powered to detect differences in OS or any other efficacy endpoints however TFST, PFS2 & TSST are significantly improved while there is a trend towards OS improvement with niraparib-bevacizumab combination. Clinical trial information: NCT02354131.

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Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study

The Lancet Oncology ◽

10.1016/s1470-2045(14)70391-2 ◽

2014 ◽

Vol 15 (11) ◽

pp. 1207-1214 ◽

Cited By ~ 328

Author(s):

Joyce F Liu ◽

William T Barry ◽

Michael Birrer ◽

Jung-Min Lee ◽

Ronald J Buckanovich ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase 2 ◽

Platinum Sensitive ◽

Phase 2 Study

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A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.18_suppl.lba5500 ◽

2014 ◽

Vol 32 (18_suppl) ◽

pp. LBA5500-LBA5500 ◽

Cited By ~ 8

Author(s):

Joyce Liu ◽

William Thomas Barry ◽

Michael J. Birrer ◽

Jung-min Lee ◽

Ronald J. Buckanovich ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase 1 ◽

Parp Inhibitor ◽

Objective Response ◽

Progression Free Survival ◽

Recurrent Ovarian Cancer ◽

Parp Inhibitors ◽

Open Label ◽

Angiogenic Therapy ◽

Platinum Sensitive

LBA5500 Background: PARP inhibitors and anti-angiogenics are clinically active in recurrent ovarian cancer (OvCa). Preclinical studies suggest these agents can synergize, and a phase 1 study showed that the combination of cediranib (ced) and olaparib (olap) is well-tolerated. We therefore compared the activity of olap alone (Olap) to combined ced and olap (Ced/Olap) in treatment of recurrent platinum-sensitive (plat-sens) high-grade serous (HGS) or BRCA-related OvCa (NCT 01116648). Methods: Patients (pts) across 9 centers were randomized 1:1 in this Ph 2 open label study to Olap (olap 400 mg capsules BID) or Ced/Olap (olap 200 mg capsules BID; ced 30 mg daily), stratified by BRCA status and prior anti-angiogenic therapy. Eligibility included pts with recurrent plat-sens HGS or BRCA-related OvCa. Pts had measurable disease by RECIST 1.1, PS 0 or 1, and the ability to take POs. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor was allowed. Progression-free survival (PFS) was defined as time from randomization to radiographic progression or death. With a target N=90 pts, the study was powered to detect a hazard ratio (HR) of 1.75 (median PFS 6 vs 10.5 mo). Results: Pts were enrolled from Oct 2011 to Jun 2013: 46 to Olap, 44 to Ced/Olap. 48 pts were known BRCA carriers (25 Olap; 23 Ced/Olap). At a planned interim analysis the DSMB recommended release of data. As of Jan 7, 2014, 41 pts had a PFS event. Median PFS was 9.0 mos for Olap and 17.7 mos for Ced/Olap (HR 2.9, 95% CI 1.5-5.6, p = 0.001). There were 2 complete responses (CR) and 21 partial responses (PR) in pts on Olap (56% objective response rate, ORR) and 3 CRs and 33 PRs in pts on Ced/Olap (84% ORR, p = 0.008). The overall rate of Gr3/4 toxicity was higher for pts on Ced/Olap (70%) than on Olap (7%). Differentially occurring toxicities included fatigue (27% Ced/Olap vs 7% Olap), diarrhea (23% vs 0%), and hypertension (39% vs 0%). Updated efficacy and exploratory subgroup analyses will be presented. Conclusions: Combined Ced/Olap significantly extended PFS and ORR compared to Olap in plat-sens OvCa. Further studies of this oral combination in plat-sens OvCa are warranted. Clinical trial information: NCT01116648.

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Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: A phase 2 study

Gynecologic Oncology ◽

10.1016/j.ygyno.2015.02.009 ◽

2015 ◽

Vol 137 (2) ◽

pp. 223-228 ◽

Cited By ~ 74

Author(s):

Clemens B. Tempfer ◽

Guido Winnekendonk ◽

Wiebke Solass ◽

Reinhard Horvat ◽

Urs Giger-Pabst ◽

...

Keyword(s):

Ovarian Cancer ◽

Recurrent Ovarian Cancer ◽

Phase 2 ◽

Phase 2 Study

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An Open-Label Phase 2 Study of Twice-Weekly Bortezomib and Intermittent Pegylated Liposomal Doxorubicin in Patients With Ovarian Cancer Failing Platinum-Containing Regimens

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e318251051a ◽

2012 ◽

Vol 22 (5) ◽

pp. 792-800 ◽

Cited By ~ 15

Author(s):

Gabriella Parma ◽

Rosanna Mancari ◽

Gianluca Del Conte ◽

Giovanni Scambia ◽

Angiolo Gadducci ◽

...

Keyword(s):

Ovarian Cancer ◽

Liposomal Doxorubicin ◽

Pegylated Liposomal Doxorubicin ◽

Phase 2 ◽

Open Label ◽

Phase 2 Study ◽

Open Label Phase

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A multicenter, open-label, expanded phase 2 study to evaluate the safety and efficacy of etirinotecan pegol, a polymer conjugate of irinotecan, in women with recurrent platinum-resistant or refractory ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2017.08.026 ◽

2017 ◽

Vol 147 (2) ◽

pp. 276-282 ◽

Cited By ~ 4

Author(s):

G. Rustin ◽

I. Vergote ◽

J.P. Micha ◽

L.R. Duska ◽

N. Reed ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase 2 ◽

Open Label ◽

Safety And Efficacy ◽

Polymer Conjugate ◽

Platinum Resistant ◽

Phase 2 Study ◽

Etirinotecan Pegol

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Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial

The Lancet Oncology ◽

10.1016/s1470-2045(19)30515-7 ◽

2019 ◽

Vol 20 (10) ◽

pp. 1409-1419 ◽

Cited By ~ 37

Author(s):

Mansoor Raza Mirza ◽

Elisabeth Åvall Lundqvist ◽

Michael J Birrer ◽

Rene dePont Christensen ◽

Gitte-Bettina Nyvang ◽

...

Keyword(s):

Ovarian Cancer ◽

Recurrent Ovarian Cancer ◽

Phase 2 ◽

Platinum Sensitive ◽

Superiority Trial

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Antitumor activity and safety of camrelizumab plus famitinib in patients with platinum-resistant recurrent ovarian cancer: results from an open-label, multicenter phase 2 basket study

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-003831 ◽

2022 ◽

Vol 10 (1) ◽

pp. e003831

Author(s):

Lingfang Xia ◽

Jin Peng ◽

Ge Lou ◽

Mei Pan ◽

Qi Zhou ◽

...

Keyword(s):

Ovarian Cancer ◽

Antitumor Activity ◽

Safety Profile ◽

Objective Response ◽

Recurrent Ovarian Cancer ◽

Synergistic Activity ◽

Phase 2 ◽

Open Label ◽

Multicenter Phase ◽

Platinum Resistant

BackgroundCombination treatments with immune-checkpoint inhibitor and antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a notable therapeutic strategy in recurrent ovarian cancer (ROC). We report the results of camrelizumab (an anti-programmed cell death protein-1 antibody) in combination with famitinib (a receptor tyrosine kinase inhibitor) for the treatment of platinum-resistant ROC from an open-label, multicenter, phase 2 basket trial.MethodsEligible patients with platinum-resistant ROC were enrolled to receive camrelizumab (200 mg every 3 weeks by intravenous infusion) and oral famitinib (20 mg once daily). All patients had disease progression during or <6 months after their most recent platinum-based chemotherapy. Primary endpoint was confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 based on investigator’s assessment. Secondary endpoints included disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS), 12-month OS rate and safety profile.ResultsOf the 37 women enrolled, 11 (29.7%) patients had primary platinum resistant, 15 (40.5%) patients had secondary platinum resistant and 11 (29.7%) patients had primary platinum refractory disease. As the cut-off date of April 9, 2021, nine (24.3%) patients had achieved a confirmed objective response, the ORR was 24.3% (95% CI, 11.8 to 41.2) and the DCR was 54.1% (95% CI, 36.9 to 70.5). Patients with this combination regimen showed a median TTR of 2.1 months (range, 1.8–4.1) and a median DoR of 4.1 months (95% CI, 1.9 to 6.3). Median PFS was 4.1 months (95% CI, 2.1 to 5.7), and median OS was 18.9 months (95% CI, 10.8 to not reached), with the median follow-up duration of 22.0 months (range, 12.0–23.7). The estimated 12-month OS rate was 67.2% (95% CI, 49.4 to 79.9). The most common ≥grade 3 treatment-related adverse events were hypertension (32.4%), decreased neutrophil count (29.7%) and decreased platelet count (13.5%). One (2.7%) patient died of grade 5 hemorrhage that was judged possibly related to study treatment by investigator.ConclusionThe camrelizumab with famitinib combination appeared to show antitumor activity in heavily pretreated patients with platinum-resistant ROC with an acceptable safety profile. This combination might provide a novel alternative treatment strategy in platinum-resistant ROC setting and warranted further exploration.Trial registration numberNCT03827837.

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