scholarly journals RaPiDS (GOG-3028): randomized Phase II study of balstilimab alone or in combination with zalifrelimab in cervical cancer

2021 ◽  
Author(s):  
David M O’Malley ◽  
Leslie M Randall ◽  
Camille Gunderson Jackson ◽  
Robert L Coleman ◽  
John L Hays ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response ◽  
Chemotherapy Patients ◽  
Investigational Agents

Balstilimab (anti-programmed death 1) and zalifrelimab (anti-CTLA-4) are two new checkpoint inhibitors that have emerged as promising investigational agents for the treatment of cervical cancer, particularly in the setting of previously-treated, recurrent/metastatic disease. Here we describe the rationale and design of RaPiDS (NCT03894215), a two-arm Phase II study evaluating the safety, tolerability and efficacy of balstilimab administered alone or in combination with zalifrelimab in patients with advanced cervical cancer who progressed after first-line, platinum-based chemotherapy. Patients will be randomized in a 1:1 ratio. The primary end point is objective response rate, and key secondary objectives include safety, duration of response, progression-free survival, overall survival and quality of life outcomes.

A phase II study of irinotecan combined with S-1 in patients with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy

2019 ◽  
Vol 29 (3) ◽  
pp. 474-479
Author(s):  
Seiji Mabuchi ◽  
Eriko Yokoi ◽  
Kotaro Shimura ◽  
Naoko Komura ◽  
Yuri Matsumoto ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Cervical Cancer ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Previously Treated ◽  
Grade 3

ObjectivesWe conducted a phase II study to investigate the efficacy and toxicities of irinotecan plus oral S-1 in patients with advanced or recurrent uterine cervical cancer.MethodsPatients with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy were enrolled. Irinotecan (150 mg/m2) was administered intravenously over the course of 90 min on day 1, and S-1 (80 mg/m2) was given orally in two divided doses from days 1 to 14 of a 21 day cycle. The primary endpoint of this phase II study was response rate. Secondary endpoints included safety, progression free survival, and overall survival.ResultsA total of 19 patients were enrolled and treated. The response rate was 29.4%. Grade 3–4 hematologic toxicities were observed in three patients (15.7%). The only grade 3–4 non-hematologic toxicity observed was grade 3 diarrhea. The median progression free survival and overall survival were 3 months and 9 months, respectively.ConclusionS-1 plus irinotecan in a 3 weekly setting is safe and active in women with advanced or recurrent cervical cancer previously treated with platinum based chemotherapy. Future corroborative clinical studies are warranted.

Real-world (rw) clinical outcomes for advanced/metastatic non-small cell lung cancer (aNSCLC) patients (pts) treated with second line (2L) ramucirumab plus docetaxel (R+D) post frontline (1L) platinum based chemotherapy plus immune checkpoint inhibitors (Pt + ICI).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20727-e20727
Author(s):  
Jeffrey Melson Clarke ◽  
Raina Mathur ◽  
Cliff Molife ◽  
Marta Batus ◽  
Victoria Jennifer Stefaniak ◽  
...  
Keyword(s):  
Disease Control ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Community Practice ◽  
Best Response ◽  
First Response ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response

e20727 Background: R+D is approved for use in pts with aNSCLC after Pt chemotherapy. With recent approvals, ICI can now be added to Pt chemotherapy (Pt + ICI) in 1L. This retrospective observational study provides an exploratory view of baseline characteristics and rw clinical effectiveness outcomes for pts receiving 2L R+D post 1L Pt + ICI. Methods: All adult pts treated with 2L R+D after 1L Pt + ICI therapy between 03/01/2015 and 06/30/2018, with ≥ 3 months follow up, were selected from the Flatiron Health EHR-derived de-identified database (n = 15). Rw clinical endpoints during R+D therapy included rw objective response rate (rwORR), rw disease control rate (rwDCR), rw best response, as well as Kaplan-Meier estimates of rw time to first response & rw duration of response. Results: Median age was 62 years, 10 pts (66.6%) were aged < 65 years, 11 (73.3%) were men, 3 (20.0%) had no history of smoking, 14 (93.3%) had non-squamous histology, 4 (26.7%) were EGFR positive, 3 (20.0%) were KRAS positive and 6 (85.7%) were PD-L1 negative. Of the 8 pts with a documented rw tumor response assessment, 3 (37.5%) had partial response (PR), 3 (37.5%) had stable disease (SD), & 2 (25.0%) had progressive disease as their rw best response. The rwORR (PR or complete response [CR]) & rwDCR (PR, CR, or SD) were 37.5% and 75.0%, respectively. Among responding pts, median time to first response was 2.2 months (95% CI, 1.3 - not reached [NR]) & median duration of response was 2.3 months (95% CI, 1.5 - NR). Patient numbers were too small (n = 15) and duration of follow-up was too short (3.4 months [IQR, 0.7 - 5.4]) to make robust estimation of overall survival or rw progression free survival. Conclusions: Data from this small patient cohort in US community practice are not conclusive and should be considered exploratory, but do show high rates of rw objective response and rw disease control rates during 2L R+D following 1L Pt + ICI. Data with larger sample sizes and additional follow-up are needed to better understand outcomes of R+D following the addition of ICI to 1L Pt chemotherapy regimens.

scholarly journals Dual PD-1 and CTLA-4 Checkpoint Blockade Using Balstilimab and Zalifrelimab Combination as Second-Line Treatment for Advanced Cervical Cancer: An Open-Label Phase II Study

2021 ◽  
Author(s):  
David M. O'Malley ◽  
Maryna Neffa ◽  
Bradley J. Monk ◽  
Tamar Melkadze ◽  
Marilyn Huang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Clinical Activity ◽  
Advanced Cervical Cancer ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Duration Of Response

PURPOSE Balstilimab (antiprogrammed death-1) and zalifrelimab (anticytotoxic T-lymphocyte–associated antigen-4) are two new checkpoint inhibitors emerging as promising investigational agents for the treatment of advanced cervical cancer. This phase II trial (ClinicalTrials.gov identifier: NCT03495882 ) evaluated the combination of balstilimab plus zalifrelimab in patients with recurrent and/or metastatic cervical cancer who relapsed after prior platinum-based therapy. PATIENTS AND METHODS Patients were intravenously dosed with balstilimab 3 mg/kg once every 2 weeks and zalifrelimab 1 mg/kg once every 6 weeks, for up to 24 months. The primary end point was objective response rate (ORR, RECIST version 1.1, assessed by independent central review). Secondary end points included duration of response, safety and tolerability, and survival. RESULTS In total, 155 women (median age, 50 years [range 24-76 years]) were enrolled and treated with balstilimab plus zalifrelimab; 125 patients had measurable disease at baseline and one prior line of platinum-based therapy in the advanced setting, and these patients constituted the efficacy-evaluable population. The median follow-up was 21 months. The confirmed ORR was 25.6% (95% CI, 18.8 to 33.9), including 10 complete responders and 22 partial responders, with median duration of response not reached (86.5%, 75.5%, and 64.2% at 6, 9, and 12 months, respectively). The ORRs were 32.8% and 9.1% in patients with programmed death ligand-1–positive and programmed death ligand-1–negative tumors, respectively. For patients with squamous cell carcinoma, the ORR was 32.6%. The overall disease control rate was 52% (95% CI, 43.3 to 60.6). Hypothyroidism (14.2%) and hyperthyroidism (7.1%) were the most common immune-mediated adverse events. CONCLUSION Promising and durable clinical activity, with favorable tolerability, was seen in this largest trial to date evaluating dual programmed death-1/cytotoxic T-lymphocyte–associated antigen-4 blockade in patients with recurrent and/or metastatic cervical cancer. Further investigation of the balstilimab and zalifrelimab combination in this setting is continuing.

Phase II study of afatinib in recurrent and/or metastatic esophageal squamous cell carcinoma (R/M ESCC) (KCSG HN14-18).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4051-4051
Author(s):  
Min Hee Hong ◽  
Yun-Gyoo Lee ◽  
Hyo Song Kim ◽  
Keon Uk Park ◽  
Hoon-Gu Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Clinical Investigation ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Open Label ◽  
Platinum Based Chemotherapy

4051 Background: Afatinib, an irreversible pan-ErbB kinase inhibitor showed anti-tumor activity against esophageal cancer in phase I trial. In this multicenter, open-label, single arm phase II study, we aimed to evaluate the activity and safety of afatinib in R/M ESCC. Methods: Patients (pts) who had ECOG PS 0-2 and had progressed on platinum-based chemotherapy for R/M ESCC were enrolled. Pts were treated with afatinib 40mg/day until disease progression, unacceptable toxicity, or patient’s refusal. Primary endpoint was objective response rate (ORR) per RECIST 1.1. The estimated sample size was 49, using a two-stage minimax design to evaluate incremental response rate from 5 to 15%. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety profile. Additionally, we try to identify biomarker to predict efficacy of afatinib with target capture sequencing and gene expression profile as exploratory endpoints. Results: In a total of 49 enrolled pts (median age 60; range 44 -84), ORR and DCR were 14.3 % and 73.3%, respectively. With a median follow-up of 6.6 months, median PFS and OS was 3.4 months (95% CI 2.2-4.6) and 6.6 months (95% CI 5.2-8.0). Median treatment duration and duration of response were 2.8 months (range, 0.4-15.3) and 7.1 months (range, 2.5-13.9), respectively. Dose reduction and interruption occurred in 19 (38.8%) and 15 (30.6 %) pts. Treatment-related adverse events (TRAE) occurred in 33 pts (67.3%) with most common TRAEs being diarrhea (n=22, 44.9%) and acneiform rash (n=12, 24.5%). G3-4 TRAEs were rare, occurring in 7 pts (14.3 %). Conclusions: Afatinib demonstrated modest efficacy with manageable toxicity in platinum-resistant R/M ESCC patients. Given the modest response rate, identification of predictive biomarkers is essential for further clinical investigation of afatinib in R/M ESCC. Those biomarkers are being analyzed and will be presented in the conference (NCT02353936). Clinical trial information: NCT02353936. [Table: see text]

NivoCUP: An open-label phase II study on the efficacy of nivolumab in cancer of unknown primary.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 106-106 ◽  
Author(s):  
Junko Tanizaki ◽  
Kan Yonemori ◽  
Kohei Akiyoshi ◽  
Hironobu Minami ◽  
Hiroki Ueda ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pathological Examination ◽  
Unknown Primary ◽  
Open Label ◽  
Previously Treated

106 Background: CUP has a poor prognosis with a median survival of less than 12 months. Given the recent approval of immune checkpoint inhibitors in several cancer types, we performed a multicenter phase II study of nivolumab in CUP patients (pts). Methods: The main population of this study is CUP pts who were previously treated with more than one line of systemic chemotherapy. Previously untreated CUP pts were also enrolled for exploratory analysis. Pathological examination (including IHC), CT, FDG-PET, gastroscopy and colonoscopy and medical examination were mandatory for diagnosis of CUP before enrollment. CUP pts belonging to favorable prognosis groups were excluded from the trial. Nivolumab (240 mg/body) was delivered as an intravenous infusion every 2 weeks for up to 52 cycles until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to RECIST 1.1 by an Independent Endpoint Review Committee in previously treated pts. The secondary objectives include investigator-assessed ORR, progression-free survival (PFS), overall survival (OS), safety and the association between the efficacy of nivolumab and PD-L1 expression. Results: A total of 56 CUP pts, 45 previously treated and 11 previously untreated pts, were enrolled in this trial. The median age was 65.5 years, 22 pts were male. Median follow-up was 8.05 mo (range, 0.1 to 20.7 mo). Of 45 previously treated pts, 2 and 9 had an investigator-assessed complete response and partial response (ORR 24.4%, 95% CI: 12.9-39.5%), with a median PFS (mPFS) and OS (mOS) of 5.4 mo (95% CI: 2.6-6.9) and 15.1 mo (95% CI: 8.3-NR), respectively. Among 11 previously untreated pts, 1 pt had partial response (ORR 9.1%, 95% CI: 0.2-41.3%). The mPFS was 3.9 mo and the mOS was not reached in untreated pts (95% CI: 1.1-5.6, and 95% CI: 2.6-NR, respectively). Nivolumab demonstrated a mPFS of 5.1mo (95% CI: 2.7-5.6) and a mOS of 15.9 mo (95% CI: 8.4-NR) in an overall population. Immune-related adverse events occurred in 57% of overall pts with 5% of grade 3 or higher, and the most common were rash (27%), hypothyroidism (16%), and diarrhea/colitis (16%). No treatment related death was observed. Conclusions: In pts with previously treated and untreated CUP, nivolumab demonstrated durable antitumor activity with a manageable safety. Clinical trial information: UMIN000030649.

A phase II study of lorlatinib in patients (pts) with ALK-positive (ALK+) lung cancer with brain-only progression.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9595-9595 ◽  
Author(s):  
Ibiayi Dagogo-Jack ◽  
Geoffrey R. Oxnard ◽  
Jessica Fink ◽  
Gianluca Diubaldi ◽  
Caitlyn Helms ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Duration Of Response ◽  
The Central Nervous System ◽  
Alk Positive

9595 Background: Lorlatinib is a 3rd-generation ALK tyrosine kinase inhibitor (TKI) developed to penetrate the central nervous system (CNS) and overcome resistance to 2nd-generation (2nd-gen) ALK TKIs. In a phase II study, lorlatinib demonstrated significant intracranial (IC) activity after failure of 2nd-gen TKIs. As treatment discontinuation for extracranial (EC) progression can confound assessment of durability of IC response, we performed a phase II study (NCT02927340) to selectively evaluate lorlatinib activity in ALK+ pts with CNS-only disease. Methods: Between 11/2016 and 1/2019, 22 pts with IC progression on an ALK TKI with no other sites of measurable disease were enrolled at 2 institutions. Pts received lorlatinib at a starting dose of 100 mg QD. The primary endpoint was the IC disease control rate (DCR) at 12 weeks per modified RECIST v1.1. Secondary endpoints were IC objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Results: Of the 22 pts enrolled, 21 (95%) had progressed on a 2nd-gen ALK TKI and 14 (64%) had previously received CNS radiation (median 21.1 months between radiation and lorlatinib). Median number of prior ALK TKIs was 2 (range 1-4). As of the data cutoff of 12/15/19, median follow-up was 14 months. At 12 weeks, the IC-DCR was 95%, including 8 pts with stable disease. Best IC ORR was 59% with 6 complete and 7 partial responses. Nine (41%) pts relapsed on study, including 3 IC-only, 5 EC-only, and 1 combined relapse. Four pts continued treatment beyond EC-only progression. Although median IC DOR and PFS were not estimable due to few progression events, the IC progression-free rate at 12 months was 81% (95% CI: 53%-94%). Twelve pts have discontinued study treatment due to progression (n = 6), edema (n = 1), pulmonary hypertension (n = 1), or transition to commercial lorlatinib (n = 4). Conclusions: Lorlatinib induces durable intracranial responses in pts with CNS-only progression on 2nd-gen ALK TKIs, suggesting that CNS-specific relapses are primarily driven by ALK-dependent mechanisms. Further studies are needed to characterize the molecular basis of sensitivity to lorlatinib in this unique subgroup of pts with ALK+ lung cancer. Clinical trial information: NCT02927340 .

scholarly journals Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial

2020 ◽  
Vol 38 (34) ◽  
pp. 4095-4106
Author(s):  
Chunyan Lan ◽  
Jingxian Shen ◽  
Yin Wang ◽  
Jundong Li ◽  
Zhimin Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Advanced Cervical Cancer ◽  
Open Label ◽  
Duration Of Response ◽  
Grade 3

PURPOSE Camrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer. METHODS This multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety. RESULTS Forty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%). CONCLUSION Camrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.

Anlotinib plus sintilimab in patients with recurrent advanced cervical cancer: A prospective, multicenter, single-arm, phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5524-5524
Author(s):  
Qin Xu ◽  
Chuanben Chen ◽  
Yang Sun ◽  
Zhangzhou Huang ◽  
Yibin Lin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cervical Cancer ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Advanced Cervical Cancer ◽  
Median Response ◽  
Platinum Based Chemotherapy

5524 Background: It is difficult for patients with recurrent advanced cervical cancer to obtain clinical benefits after the failure of standard chemotherapy. However, antiangiogenic therapy combined with immune checkpoint inhibitors have become a promising strategy for advanced cervical cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor, inhibiting tumour angiogenesis and proliferative signalling. Sintilimab is a fully humanized, high-affinity monoclonal antibody against programmed cell death-1 (PD-1). This phase II, single-arm study (ChiCTR1900023015) aims to evaluate the efficacy and safety of anlotinib plus sintilimab in patients with recurrent advanced cervical cancer. Methods: Patients who have received at least once platinum-based chemotherapy, histopathologically confirmed recurrent advanced cervical cancer (including squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma), more than 1% PD-L1 expression, ECOG 0-1 were considered eligible for enrollment. Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle), and sintilimab was administered intravenously (200mg once every 3 weeks). The treatment was continued until disease progression, death or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: Between September 2019 and February 2021, 42 patients with a median age of 52 years (range:47-58), FIGO histopathological stage I (11.9%), II (31.0%), III (33.3%), IV (9.5%) and undiagnosed (14.3%) were enrolled. 39 of these patients were evaluable. In the efficacy-evaluable population (n = 39), the therapeutic evaluation showed that 2 and 20 patients achieved complete response and partial response respectively, yielding the ORR of 56.4% (22/39, 95% CI:40.2 to 71.5). The DCR was 94.9% (37/39, 95% CI:80.7 to 98.8). The median response time was 1.6 months. The median PFS was not reached. The most common adverse events (AEs) were grade 1 or 2, which included hypothyroidism (33.3%), hypertension (23.8%), AST (21.4%), diarrhea (19.0%), ALT (16.7%), hand-foot syndrome(14.3%), hypertriglyceridemia (14.3%) and anemia (11.9%). The grade 3 AEs were hypertension (4.8%), hyponatremia (4.8%), immune pneumonia (2.4%) and immune myocarditis (2.4%). No higher AEs and treatment-related death were observed. Conclusions: Anlotinib plus sintilimab showed a promising efficacy with a favorable toxicity profile for patients with recurrent advanced cervical cancer. We will report more data in the future. Clinical trial information: ChiCTR1900023015.

A multicenter phase II study of the efficacy and safety of quisinostat (an HDAC inhibitor) in combination with paclitaxel and carboplatin chemotherapy (CT) in patients (pts) with recurrent platinum resistant high grade serous epithelial ovarian, primarily peritoneal or fallopian tube carcinoma cancer (OC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5541-5541 ◽  
Author(s):  
Sergei Tjulandin ◽  
Mikhail Fedyanin ◽  
Vladimir Ivanovich Vladimirov ◽  
Vladimir Kostorov ◽  
Alla Sergeevua Lisyanskaya ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Hdac Inhibitors ◽  
Progression Free Survival ◽  
Good Tolerability ◽  
Platinum Resistant ◽  
Duration Of Response ◽  
Orally Bioavailable ◽  
Number Of Cycles

5541 Background: Quisinostat is an orally bioavailable potent pan-histone deacetylase inhibitor. Combinations of HDAC inhibitors with paclitaxel or cisplatin demonstrate promising results in preclinical models with cisplatin and paclitaxel resistant OC. In phase Ib study the dosage of Quisinostat in combination of paclitaxel and carboplatin recommended for the phase II study was 12 mg. We report results of the phase II study of Quisinostat in combination with paclitaxel and carboplatin in pts with recurrent platinum resistantOC. Methods: the main inclusion criteria was tumor progression observed not less than 1 month and no more than 6 months after completion of the planned number of cycles of 1st line platinum/paclitaxel based CT. Quisinostat was administered at dose 12 mg p.o. each 3 week cycle on Days 1, 3, 5, 7, 9, 11 with of paclitaxel (175 mg/m2) and carboplatin (AUC5) on Day 7 of each cycle, for 2ndline. Pts received up to 6 cycles. The primary efficacy endpoint is the objective response rate (ORR) verified by the ICR. The secondary endpoints include safety, progression free survival (PFS) and overall survival. The study design implies the use of the two-stage Simon model: 29 patients who underwent treatment would provide 80% power for hypothesis testing in order to frequency of the ORR 30% (α = 0.05). Results: 31 pts were enrolled (30 pts evaluated). Median age was 57 years. Twenty one pts (67.7%) received all 6 cycles of therapy. ORR was 50.0% (15 pts). Median duration of response was 5 months (4.2-5.7). Median PFS - 6 months (95%CI 4.4-7.6). Any SAE were seen in 16.1% pts, AE of grade 3 and 4 – in 71% and 48.4% pts temporarily discontinued therapy due to AE. Dose reduction of CT due to AE was performed in 22.6% pts. The most common adverse events were neutropenia – 67,7%, nausea – 61.3%, weakness – 29%, thrombocytopenia – 22.6%, neuropathy – 19.4%, vomiting – 19.4%. Conclusions: Quisinostat in combination with paclitaxel and carboplatin in pts with recurrent platinum resistant ovarian cancer showed high efficacy and good tolerability Clinical trial information: NCT02948075.

A phase I/II study of nivolumab plus or minus ipilimumab in combination with multifraction stereotactic radiosurgery for recurrent high-grade radiation-relapsed meningioma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2073-TPS2073
Author(s):  
Jiayi Huang ◽  
Jian Li Campian ◽  
Feng Gao ◽  
Tanner Michael Johanns ◽  
Annick Desjardins ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Molecular Signature ◽  
High Grade ◽  
Eligibility Criteria ◽  
Duration Of Response ◽  
Treatment Escalation

TPS2073 Background: There is currently lack of effective therapy for meningiomas that have relapsed despite surgery and radiation therapy (RT). Reirradiation have been used in selected cases, but the long-term clinical outcomes remained poor, especially for high-grade meningiomas. Preclinical data have suggested synergy between hypofractionated radiosurgery with immune checkpoint inhibitors such as PD1 and CTLA4 inhibitors. The purpose of this study is to evaluate feasibility and preliminary clinical efficacy of combining reirradiation using hypofractionated radiosurgery with concurrent nivolumab (PD1 inhibitor) plus or minus ipilimumab (CTLA4 inhibitor) for recurrent high-grade meningiomas. Methods: During the phase I portion, eligible patients will be treated according to treatment-escalation schema following the modified 3+3 design (Table). The maximum tolerated combination (MTC) will be the regimen at which ≤1/6 patients experience dose-limiting toxicity within 8 weeks of the start of study therapy. During the phase II portion, a total of 24 evaluable patients will be enrolled at the MTC using Simon’s MiniMax two-stage design. Key eligibility criteria include patients with recurrent grade II-III meningiomas after prior RT; age ≥ 18 years; ECOG score ≤ 2; measurable disease but ≤ 5 cm (or 20 cm3); prior radiation dose ≤ 70 Gy with at least 6 months interval; normal organ function; no active autoimmunity. The primary endpoints are to determine the MTC (phase I) and the objective response rate of the MTC (phase II). Secondary endpoints include safety, duration of response, progression-free survival, overall survival. Exploratory endpoints include developing an immune or molecular signature for predicting treatment response and resistance. The trial is actively enrolling and funded by the National Cancer Institute Experimental Therapeutics Clinical Trials Network (NCI-ETCTN). Treatment Escalation Schema. Clinical trial information: NCT03604978. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document