Preliminary results of anlotinib and niraparib dual therapy evaluation in platinum-resistant recurrent ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17532-e17532
Author(s):  
Guochen Liu ◽  
Jihong Liu ◽  
Bingna Xian ◽  
Jing Li ◽  
Yanling Feng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Skin Reaction ◽  
Group Performance ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Recurrent Ovarian Cancer ◽  
Platinum Resistant ◽  
Hand Foot Skin Reaction

e17532 Background: Patients with platinum-resistant ovarian cancer have a poor prognosis. Effective treatment options for these patients are limited. Combination of PARP inhibitors and antiangiogenic therapy is reported as an effective antitumor strategy. In this study (ANNIE), we evaluate the activity of niraparib combined with anlotinib in patients with platinum resistant recurrent ovarian carcinoma. Methods: The ANNIE trial (ClinicalTrials.gov identifier NCT04376073) was a multicentre, single-arm, phase 2 study that evaluated the safety and activity of niraparib combined with anlotinib in patients (≥18 & ≤70 years, an Eastern Cooperative Oncology Group performance status of 0 or 1) with recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer cancer whose disease recurred in less than 6 months after the last administered platinum therapy, and with measurable disease according to the Response Evaluation Criteria in Solid Tumors. Patients received oral niraparib 300mg/200mg once daily continuously and anlotinib 12mg (The initial dose was reduced to 10mg on November 1, 2020) on day 1-14 of each 21-day cycle thereafter until disease progression or intolerable toxicity. The primary objective was to assess objective response rate (ORR; complete plus partial responses) according to RECIST version 1.1. 40 cases are planned to be enrolled. Results: Between May 22, 2020 and February 6, 2021, we enrolled 33 patients (median age, 56 years [range, 37-69 years]). Patients had received a median of six (range, 2-9) previous lines of therapy. The cut-off date of analysis was February 4, 2021, the median follow-up was 4.1 months (range, 0.1–8.1). At data cutoff, all but seven (2 voluntarily withdrew, 5 with progressive disease) of the patients were still on treatment. Twenty-five patients underwent imaging evaluation. The confirmed best overall response assessment showed 12 with partial responses, 12 with stable disease, yielding the ORR of 48.0% (95% CI, 27.0%̃69.0%). The median duration of response and the median PFS were not reached. Drug-related grade 3 or worse treatment-emergent adverse events were occurred in 39.4% patients, including hand-foot skin reaction (3 pts), thrombocytopenia (2 pts), hypertriglyceridemia (2 pts), neutropenia (2 pts), anemia (1 pts) and hypertension (1 pts). The most common treatment emergent adverse events were hand-foot skin reaction (36.4%), hypertension (36.4%), and thrombocytopenia (33.3%). No treatment-related death was recorded. Enrollment was ongoing so far. Conclusions: Niraparib in combination with anlotinib showed promising antitumor activity and tolerable toxicity in patients with platinum resistant recurrent ovarian cancer. The conclusion can be clarified after the research is completed. Clinical trial information: NCT04376073.

Anlotinib plus pemetrexed as a further treatment for patients with platinum-resistant ovarian cancer: A single-arm, open-label, phase II study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5533-5533
Author(s):  
Jueming Chen ◽  
Wei Wei ◽  
Lie Zheng ◽  
Han Li ◽  
Yanling Feng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Open Label ◽  
Platinum Resistant ◽  
Grade 3

5533 Background: Non-platinum chemotherapy is widely used in platinum-resistant recurrent ovarian cancer treatment but with limited efficacy. Combing chemotherapy with angiogenic inhibitors is a new therapeutic choice. Anlotinib is a novel tyrosine kinase inhibitor targeting multiple receptors involved in tumor proliferation, vasculature, and tumor microenvironment. The study aimed to further assess the efficacy and safety of anlotinib combined with pemetrexed in platinum-resistant ovarian cancer. Methods: Patients who had received at least two different chemotherapy regimens (including the first line platinum-based regimen), with histologically proven recurrent platinum-resistant or platinum-refractory epithelial ovarian cancer (including salpingocarcinoma and peritoneal carcinoma), ECOG 0-2, were considered eligible for enrollment to receive six 21-days cycles of anlotinib (12 mg QD from day 1 to 14; 21 days per cycle) orally plus pemetrexed intravenously (0.5 g/m2 on day 1; 21 days per cycle). Subsequent maintenance treatment was anlotinib monotherapy (12 mg QD from day 1 to 14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint was objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety. Results: As of Jan 2021, 27 patients were enrolled. The median number of chemotherapy was 4 (range, 2-10) and 51.9% (14/27) of patients had ever received antiangiogenic therapy. The ORR was 36.4% (partial response (PR) in 8 patients; 95% CI, 17.2-59.3). The DCR was 100.0% (PR in 8 patients and stable disease (SD) in 14 patients; 95% CI, 73.5-100). The median time of the first response was 1.6 months (range, 1.3-4.4). The median PFS was 9.3 months (95% CI, NE-NE). Furthermore, the ORR of patients with and without prior antiangiogenic therapy was 16.7% (95%CI, 2.1-48.4) and 60.0% (95%CI, 26.2-87.8) respectively (P = 0.074). Any grades of adverse events (AEs) were observed in 92.6% (25/27) of patients, containing allergic eruption (33.3%), hand-foot syndrome (29.6%), hypertension (25.9%), and fatigue (25.9%). The grade 3-4 adverse events were only observed in 5 patients, including 1 with grade 3 proteinuria, 1 with grade 3 ascites, 1 with grade 3 fatigue, 1 with grade 3 edema limbs and 1 with grade 4 anemia. Conclusions: The treatment of anlotinib plus pemetrexed showed a promising antitumor activity with tolerable toxicity for patients in platinum-resistant and refractory ovarian cancer. Clinical trial information: ChiCTR2000029654.

An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer (KGOG 3045, AMBITION).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5520-5520
Author(s):  
JUNG-YUN LEE ◽  
Byoung-Gie Kim ◽  
Jae-Weon Kim ◽  
Jung Bok Lee ◽  
Eunhyang Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Targeted Therapy ◽  
Adverse Events ◽  
Synergistic Effects ◽  
Single Agent ◽  
Objective Response ◽  
Complete Response ◽  
Recurrent Ovarian Cancer ◽  
Weekly Paclitaxel ◽  
Platinum Resistant

5520 Background: Heavily treated platinum-resistant ovarian cancer remains a therapeutic challenge. Although standard therapy includes non-platinum single agent chemotherapy (CT), prognoses are very poor in this setting. Anticancer therapies based on molecular biomarkers have improved dramatically. We report data from an umbrella study of biomarker-driven targeted therapy (olaparib, O; cediranib, C; durvalumab, D; tremelimumab, T) in platinum-resistant recurrent ovarian cancer (NCT03699449). Methods: Patients with platinum-resistant ovarian cancer with ≥ two lines of prior chemotherapy and ECOG 0/1 were eligible for this study. In the screening phase, archival tumor samples were tested for HRD and PD-L1 status. Treatment arms were allocated according to the test results. For HRD+ patients, we tested the synergistic effects of O with other agents: patients were randomly allocated to arm 1, O+C (O 200mg bid + C 30mg qd); or arm 2, O+D (O 300mg bid + D 1500mg q4w). For HRD- patients, we tested the role of biomarker-driven immunotherapy according to PD-L1 expression: arm 3, D+CT (D 1500mg q4w + PLD or topotecan or weekly paclitaxel [6 cycles]) in patients with high PD-L1 expression; arm 4, D+T75+CT (D 1500mg q4w + T 75mg q4w [4 doses] + PLD or topotecan or weekly paclitaxel [4 cycles]) in patients with low PD-L1 expression; or arm 5, D+T300+CT (D 1500mg q4w + T 300mg [1 dose] + weekly paclitaxel [60mg/m2 D1,8,15 q4w for 4 cycles]) in patients with low PD-L1 expression. Recruitment to arm 5 was initiated after completion in arm 4. The primary endpoint was objective response rates (ORR) according to RECIST 1.1. Results: Between Dec 2018 and Oct 2020, 70 patients were allocated to treatment as follows: arm 1 (n = 16), arm 2 (n = 14), arm 3 (n = 5), arm 4 (n = 18), and arm 5 (n = 17). Median age was 57 years (range 34-77) and median prior lines of treatment was 3 (range: 2-10). Among all patients, the ORR was 35.7% (25/70, 95% CI: 24.6%-48.0%); complete response was observed in two patients. The ORRs (95% CI) for each treatment arm were shown (Table). Treatment-related grade 3/4 adverse events were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients in each treatment arm, respectively. No treatment-related adverse events (TRAEs) leading to discontinuation of treatment and no grade 5 TRAEs were observed. Conclusions: This is the first biomarker-driven umbrella study conducted in patients with platinum-resistant recurrent ovarian cancer. This umbrella study provides preliminary evidence on the clinical benefit of biomarker-driven targeted therapy. All regimens were manageable, without unexpected toxicities. Clinical trial information: NCT03699449. [Table: see text]

Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5599-TPS5599
Author(s):  
Rebecca Christian Arend ◽  
Bradley J. Monk ◽  
Thomas J. Herzog ◽  
Jonathan A. Ledermann ◽  
Kathleen N. Moore ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
Ca 125 ◽  
Recist 1.1 ◽  
Platinum Resistant ◽  
Phase Iii Study

TPS5599 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism of action that includes a broad antiangiogenic effect and induction of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer showed that VB-111 in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58% with a trend for improved survival. The favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent platinum-resistant epithelial ovarian cancer with measurable disease (RECIST 1.1), and may have been previously treated with up to 5 prior lines of therapy. Patient are randomized 1:1 to receive VB-111 (1x1013 VPs) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The efficacy endpoints are OS, PFS and ORR by RECIST 1.1 and by CA-125 (GCIG criteria). A pre-planned interim analysis was performed by the DSMC in the first 60 patients evaluable for CA-125 response. The analysis met the pre-defined criteria of a CA-125 ORR (GCIG) in the treatment arm at least 10% higher than in the control arm. Study enrolment is ongoing and over 220 patients were enrolled in the US, EU, and Israel. Enrolment of the full sample size of 400 patients is expected to complete by the end of 2021. Clinical trial information: NCT03398655.

scholarly journals Axitinib plus avelumab in the treatment of recurrent glioblastoma: a stratified, open-label, single-center phase 2 clinical trial (GliAvAx)

2020 ◽  
Vol 8 (2) ◽  
pp. e001146
Author(s):  
Gil Awada ◽  
Laila Ben Salama ◽  
Jennifer De Cremer ◽  
Julia Katharina Schwarze ◽  
Lydia Fischbuch ◽  
...  
Keyword(s):  
Adverse Events ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Synergistic Activity ◽  
Open Label ◽  
Corticosteroid Dose

BackgroundNo treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB.MethodsAdult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids. Patients with a daily dose of ≤8 mg of methylprednisolone (or equivalent) initiated treatment with axitinib (5 mg oral two times per day) plus avelumab (10 mg/kg intravenous every 2 weeks) (Cohort-1). Patients with a higher baseline corticosteroid dose initiated axitinib monotherapy; avelumab was added after 6 weeks of therapy if the corticosteroid dose could be tapered to ≤8 mg of methylprednisolone (Cohort-2). Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria, served as the primary endpoint.ResultsBetween June 2017 and August 2018, 54 patients (27 per cohort) were enrolled and initiated study treatment (median age: 55 years; 63% male; 91% Eastern Cooperative Oncology Group Performance Status 0–1). Seventeen (63%) patients treated in Cohort-2 received at least one dose of avelumab. The 6-m-PFS% was 22.2% (95% CI 6.5% to 37.9%) and 18.5% (95% CI 3.8% to 33.2%) in Cohort-1 and Cohort-2, respectively; median overall survival was 26.6 weeks (95% CI 20.8 to 32.4) in Cohort-1 and 18.0 weeks (95% CI 12.5 to 23.5) in Cohort-2. The best objective response rate was 33.3% and 22.2% in Cohort-1 and Cohort-2, respectively, with a median duration of response of 17.9 and 19.0 weeks. The most frequent treatment-related adverse events were dysphonia (67%), lymphopenia (50%), arterial hypertension and diarrhea (both 48%). There were no grade 5 adverse events.ConclusionThe combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB.

A pilot study on cisplatin-based transarterial chemoembolization combined with systemic cisplatin plus gemcitabine for advanced or metastatic intrahepatic cholangiocellular carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15629-e15629
Author(s):  
Sadahisa Ogasawara ◽  
Yoshihiko Ooka ◽  
Eiichiro Suzuki ◽  
Harutoshi Sugiyama ◽  
Akinobu Tawada ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Transarterial Chemoembolization ◽  
Group Performance ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Cholangiocellular Carcinoma ◽  
Gelatin Sponge ◽  
Treatment Schedule ◽  
Intrahepatic Cholangiocellular Carcinoma

e15629 Background: Systemic cisplatin plus gemcitabine (CisGem) is the standard treatment for patients with advanced or metastatic intrahepatic cholangiocellular carcinoma (ICC). Transarterial chemoembolization (TACE) is a treatment procedure for patients with liver cancer. This prospective study was to evaluate the safety and efficacy of cisplatin-based TACE combined with systemic CisGem in patients with ICC. Methods: Eligibility criteria were histologically or cytologically confirmed, unresectable, recurrent or metastatic mass-forming type ICC; Eastern Cooperative Oncology Group performance status 0–2; and an adequate major organ function. Patients may have had prior treatment, including surgery, but no prior CisGem therapy. Cisplatin (25 mg/m2) plus gemcitabine (1000 mg/m2) were intravenously administered on days 1 and 8 of a 21-day cycle for 12 cycles. Three sessions of TACE were scheduled—before first, fifth, and ninth cycle of CisGem. A suspension of CDDP-powder 35 mg/m2 and lipiodol was injected through tumor-feeding branch of intrahepatic lesions, and embolization of the feeding arteries was performed using gelatin sponge (UMIN000004776). Results: Of 14 patients enrolled between December 2010 and December 2013, 7 (50%) completed treatment schedule, whereas 4 (29%) and 3 (21%) discontinued due to disease progression and adverse events (one patients each due to allergic reaction, platelet count reduction, and hepatic infection), respectively. The most common severe adverse events were elevated aspartate aminotransferase (86%) and alanine aminotransferase (71%) levels; reduced neutrophil (36%), platelet (36%), and white blood cell (28%) counts; and hepatic infection (21%). Eleven patients (79%) were evaluated for objective response (RECIST version 1.1): 9 were observed to have a partial response and 2 had a stable disease. The 6-month progression-free survival rate was 64%, and median overall survival was 25.8 months. Conclusions: Cisplatin-based TACE combined with CisGem is a feasible treatment option; however, a randomized clinical trial for comparison with CisGem is required in future. Clinical trial information: UMIN000004776.

Anlotinib in combination with TQB2450 in patients with recurrent ovarian cancer (ACTION): A multicenter, single-arm, open-label, phase Ib trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5557-5557
Author(s):  
Chunyan Lan ◽  
Jing Zhao ◽  
Fan Yang ◽  
Rong Li ◽  
Yu Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Group Performance ◽  
Gynecologic Cancer ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Ovarian Cancer ◽  
Open Label ◽  
Phase Ib ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response

5557 Background: Combination of antiangiogenic therapy and immune checkpoint inhibitor therapy is reported as an effective antitumor strategy. TQB2450 is a humanized IgG1 monoclonal antibody against programmed death-ligand 1 (PD-L1). We aimed to assess the activity and safety of TQB2450 plus the antiangiogenic multi-target tyrosine kinase inhibitor anlotinib in patients with recurrent advanced ovarian cancer. Methods: The study with ClinicalTrials.gov identifier NCT04236362 is an open-label, multicohort, and multicenter phase Ib trial evaluating the efficacy and safety of anlotinib combined with TQB2450 in patients with advanced gynecologic cancer. The present study (ACTION study) reports the ovarian cancer cohort. We enrolled patients aged 18–70 years with platinum-resistant or platinum-refractory epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, an Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST). Eligible patients received anlotinib 12 mg per day orally on days 1 to 14 and TQB2450 1200 mg intravenously on day 1, every three weeks. Treatment continued until disease progression, unacceptable toxicity, and withdrawal of consent. The primary endpoint was objective response rate (ORR) assessed by investigators according to RECIST version 1.1. Secondary endpoints included progression-free survival (PFS), duration of response (DOR), overall survival (OS) and safety. Results: Between 21 Feb 2020 and 15 Jan 2021, 33 patients with a median age of 55 years (range, 26-71) were enrolled and received study treatment. Patients had received at least once platinum-based chemotherapy, and the median number of previous chemotherapy lines was 3 (range, 1–6). 30.3% patients had bevacizumab therapy before enrollment. At data cutoff (15 Jan 2021), the median follow-up was 5.1 months (range, 0.1–10.8). In the 25 efficacy-evaluable patients, 13 of them achieved partial response, yielding the ORR of 52.0% (95% CI, 30.4%–71.6%). The median PFS was 6.7 months (95% CI, 4.5 months to not reached). The median duration of response and the median OS were not reached. The treatment-related grade 3 or 4 adverse events (AEs) occurred in 54.5% patients, and the most common ones were palmar-plantar erythrodysesthesia syndrome (21.2%) and hypertension (18.2%). The most potential immune-related AEs included grade 1 to 2 hypothyroidism (24.2%) and fatigue (9.1%). No treatment-related death was recorded. Conclusions: Anlotinib plus TQB2450 showed encouraging antitumor activity and tolerable toxicity in patients with recurrent advanced ovarian cancer. Clinical trial information: NCT04236362.

185 Camrelizumab monotherapy or combination therapy in patients with recurrent or metastatic cervical and endometrial carcinoma:a retrospective study

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A199-A199
Author(s):  
Hong Liu ◽  
Shuhuai Niu ◽  
Zhaohui Fang ◽  
Xi Chen ◽  
Qianying Zhang
Keyword(s):  
Combination Therapy ◽  
Adverse Events ◽  
Endometrial Carcinoma ◽  
Group Performance ◽  
Antitumour Activity ◽  
Performance Status ◽  
Treatment Options ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival

BackgroundPatients with recurrent or metastatic cervical and endometrial carcinoma have poor prognosis and few treatment options. Blocking the interaction between PD-1 and its ligands is a promising treatment strategy. Camrelizumab is a humanised anti-programmed death-1 (anti PD-1) antibody. This study aimed to assess the anti-tumour activity and safety of camrelizumab in patients with recurrent or metastatic cervical and endometrial carcinoma.MethodsWe performed a retrospective analysis for recurrent or metastatic cervical and endometrial carcinoma patients. Eligible patients were aged 28–73 years with an Eastern Cooperative Oncology Group performance status of 0 or 2. Patients received camrelizumab alone(200 mg iv d1 q2w)or in combination with chemoradiotherapy/chemotherapy. The primary endpoint was objective response (ORR). The secondary endpoints included disease control rate (DCR), median progression-free survival (mPFS) and safety.ResultsA total of 21 patients were enrolled between September 20, 2019, and July 8, 2020. 18 patients were evaluated for efficacy and 21 patients were available for safety analysis. For 18 evaluated patients, the ORR and DCR was 50% (9/18) and 83.3% (15/18), respectively. In addition, 4 patients received camrelizumab monotherapy with the ORR of 0% (0/4) and DCR of 25% (1/4), and 14 patients received camrelizumab combination therapy with the ORR of 64.3% (9/14) and DCR of 100% (14/14). 16 of 21 patients were still receiving the treatment, the median PFS was not yet achieved. Exploratory analysis showed that patients with reactive cutaneous capillary endothelial proliferation (RCCEP) had the higher objective response rate than those without RCCEP (57.1% vs 45.5%). Treatment-related adverse events occurred in 47.6% (10/21) of patients, and the most common adverse events were RCCEP (33.3%), rash (14.3%), dry skin (9.5%). Treatment-related grade 3 adverse events occurred in 4.8% (1/21) of patients.ConclusionsCamrelizumab showed antitumour activity in recurrent or metastatic cervical and endometrial carcinoma with manageable toxicities. Camrelizumab combination therapy had better efficacy compared with monotherapy. RCCEP occurrence was positively associated with outcomes of camrelizumab. Further studies are needed to verify this data.

scholarly journals 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

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.

Bevacizumab in patients with advanced platinum-resistant ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5006-5006 ◽  
Author(s):  
S. A. Cannistra ◽  
U. Matulonis ◽  
R. Penson ◽  
R. Wenham ◽  
D. Armstrong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Prior Chemotherapy ◽  
Multiple Tumor ◽  
Platinum Resistant ◽  
Phase Ii Studies ◽  
Duration Of Response

5006 Background: Bevacizumab (BV), a recombinant, humanized monoclonal antibody directed against vascular endothelial growth factor, has demonstrated clinical benefit in multiple tumor types. Activity in ovarian cancer (OC) has been reported in phase II studies in patients (pts) with recurrent disease. We now describe the activity/safety of BV in pts with platinum-resistant OC (PROC) that progressed after topotecan or liposomal doxorubicin (LD). Methods: Eligibility criteria for this multicenter, Phase II study included primary or secondary PROC that progressed within 3 months of topotecan or LD, 3 or fewer prior chemotherapy regimens, and a performance status (PS) 0 or 1. BV was dosed at 15 mg/kg q 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) as defined by RECIST. A two-stage design was utilized with H1 set at 15%. Secondary endpoints included progression-free survival (PFS), duration of response, overall survival (OS), and safety. Results: The study enrolled 44 of the intended 53 pts, closing early due to a higher than expected rate of gastrointestinal perforations (GIP). Baseline characteristics included median age 60 yrs (range 31–87); PS 0 in 26 pts, 1 in 18 pts; 2 prior chemotherapy regimens in 20 pts, 3 in 24 pts. Preliminary efficacy: ORR (CR+PR), 7/44 (16%). Median duration of response was 12 weeks, with 2 pts continuing on study >5 months. Serious adverse events (SAEs) were reported in 18/44 pts (41%). Selected SAEs included GIP 5 (11%; one occurred more than 30 days after coming off study while on paclitaxel and commercial Avastin®), bowel obstruction 5 (11%), arterial thromboembolic events 4 (9%), delayed wound healing 2 (5%), and one case each of pulmonary hypertension, hypertensive encephalopathy, and hypoxia. Conclusions: BV has single agent activity in women with PROC, but is associated with substantial toxicity in this population. Trials are ongoing in less heavily treated, newly diagnosed pts with OC to evaluate the efficacy and safety of BV in these disease settings. Identification of risk factors for BV-associated adverse events requires further study. [Table: see text]

Randomized Phase III Study of Canfosfamide in Combination With Pegylated Liposomal Doxorubicin Compared With Pegylated Liposomal Doxorubicin Alone in Platinum-Resistant Ovarian Cancer

2010 ◽  
Vol 20 (5) ◽  
pp. 772-780 ◽  
Author(s):  
Ignace Vergote ◽  
Neil J. Finkler ◽  
James B. Hall ◽  
Ostap Melnyk ◽  
Robert P. Edwards ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Liposomal Doxorubicin ◽  
Objective Response ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Positive Trend ◽  
Platinum Resistant ◽  
Platinum Refractory

Objective:To evaluate the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (OC).Methods:Patients with platinum-refractory or -resistant (primary or secondary) OC were randomized to receive canfosfamide at 1000 mg/m2 and PLD at 50 mg/m2 intravenously or PLD alone at 50 mg/m2 intravenously on day 1 every 28 days until tumor progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Other end points were objective response rate and safety. The study was originally planned for 244 patients. The trial was temporarily placed on hold after 125 patients were randomized while the results of another trial were being reviewed and the sponsor decided not to resume enrollment. The interim analysis became the final analysis.Results:The median PFS was 5.6 months for canfosfamide + PLD (n = 65) versus 3.7 months for PLD (n = 60) (hazards ratio, 0.92; P = 0.7243). A preplanned subgroup analysis showed that 75 patients with platinum-refractory or primary platinum-resistant OC had a median PFS of 5.6 months for canfosfamide + PLD versus 2.9 months for PLD (hazards ratio, 0.55; P = 0.0425). Hematologic adverse events were 66% on the canfosfamide + PLD arm versus 44% on the PLD arm, manageable with dose reductions. Nonhematologic adverse events were similar for both arms. The incidence of palmar-plantar erythrodysesthesia and stomatitis was lower on canfosfamide + PLD (23%, 31%, respectively) versus (39%, 49%, respectively) on PLD.Conclusions:Overall median PFS showed a positive trend but was not statistically significant. The median PFS in the platinum-refractory and primary platinum-resistant OC patients was significantly longer for canfosfamide + PLD versus PLD. Canfosfamide may ameliorate the palmar-plantar erythrodysesthesia and stomatitis known to be associated with PLD. Further study of this active well-tolerated regimen in platinum-refractory and primary platinum-resistant OC is planned.This study was registered at www.clinicaltrials.gov: NCT00350948.

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