FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab for patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction as second-line therapy: Interim safety and efficacy results from the phase II RAMIRIS Study (AIO-STO-0415) of the German Gastric Group at AIO.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4023-4023 ◽  
Author(s):  
Sylvie Lorenzen ◽  
Peter C. Thuss-Patience ◽  
Claudia Pauligk ◽  
Eray Goekkurt ◽  
Thomas Jens Ettrich ◽  
...  
Keyword(s):  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Safety Analysis ◽  
Treated Group ◽  
Phase Iii ◽  
Response Analysis ◽  
Second Line ◽  
Study Results ◽  
Line Setting

4023 Background: Ramucirumab as monotherapy and in combination with paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. For those pts, the benefit of a combination of ramucirumab and paclitaxel is unclear, and physicians would choose an irinotecan-based regimen as second line treatment. This provides a rationale for the evaluation of FOLFIRI + ramucirumab. Methods: This is a multicenter, randomized, investigator initiated, phase II trial, planned to include 111 pts with advanced GEA to receive 2:1 either FOLFIRI plus ramucirumab every two weeks (Arm A) or paclitaxel (days 1, 8, 15 of a 28-day cycle) plus ramucirumab every two weeks (Arm B). Primary endpoint is 6-months OS rate. This abstract displays interim results of safety and overall objective response (ORR) in docetaxel pre-treated group from up to 65 randomized pts. The results were needed to decide on conducting a subsequent phase III study. Results: 58 (A, 36; B, 22) pts were included in the safety analysis and 50 pts with tumor assessment in the response analysis. Main ≥ grade 3 adverse events were respectively in arms A/B: neutropenia (20%/22%), fatigue (6%/0%), diarrhea (8%/3%), and related SAEs (14% v 23%). Twenty-nine of 50 pts (58%) were pre-treated with docetaxel. In these pts, ORR was 30% in Arm A (5/17) and 8% (1/12) in Arm B. Disease control rate (DCR) was 65% and 50% for Arm A and B respectively. Conclusions: The interim safety analysis of the RAMIRIS trial has demonstrated feasibility of the combination of FOLFIRI and ramucirumab. Docetaxel pre-treated pts had higher ORR and DCR when ramucirumab is combined with FOLFIRI, instead of paclitaxel. EudraCT: 2015-005171-24. Clinical trial information: NCT03081143.

Activity and survival benefit of second-line chemotherapy (2L-Ctx) in advanced pancreatic adenocarcinoma (APC): Pooled analysis of the literature.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15019-e15019 ◽  
Author(s):  
MinYuen Teo ◽  
Raymond S. McDermott
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Survival Benefit ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Line Setting ◽  
Line Chemotherapy

e15019 Background: Many clinicians adopt a nihilistic approach to the management of APC. Delivery of 2L-Ctx is relatively uncommon and no recognized standard exists. We sought to examine the published activity of chemotherapy in the 2nd line setting, and the rate of 2L-Ctx delivery and its influence on reported overall survival in 1st line trials. Methods: 1st and 2L-Ctx randomized trials published between 2000 and 2012 were identified from Pubmed, and manuscripts were obtained for data extraction. Pooled weighted objective response rates (ORR) and disease control rates (DCR) were calculated. For 1st line studies, the percentage of patients who received 2L-Ctx were extracted and plotted against reported median overall survival (OS) and post-progression survival (PPS), defined as arithmetic difference between median OS and progression-free survival. Spearman correlation and linear regression were performed. Results: Sixty nine 2L Ctx studies (77 arms, n=2859) were identified. Majority received prior gemcitabine-based chemotherapy. Pooled ORR was 6.6% (95% CI 5.6 – 7.6%) and DCR was 36.7% (34.5 – 38.0%). When only prospective studies were evaluated (42 studies, 48 arms, n=1546), ORR was 5.0% (3.8 – 6.2%) and DCR was 33.9% (31.0 – 36.9%). Exploratory analysis suggested that intensification of gemcitabine-based therapy (ORR: 10.0%; DCR: 54.7%) might be marginally more active than fluoropyrimidine (7.6%; 32.2%) or taxane based 2L-Ctx (5.2%; 33.6%). 28/52 identified 1st line studies (54%) reported the percentage of patients treated with second-line chemotherapy (11 phase II, 28 arms, n=1450; 17 phase III, 33 arms, n=5051). Percentage of 2L-Ctx delivery ranged from 14 – 68% and correlated with OS (r=.49 [.26 – .67], p<.01) and PPS (r=.57 [.36 – .72], p<.01). When phase II studies were excluded, correlation was improved for OS (r=.63 [.35 – .81], p<.01) and PPS (r=.79 [.59 – .89], p<.01). Percentage of locally advanced disease did not correlate with OS/PPS nor affect prior analysis. Conclusions: Whilst awaiting further advancement in the 1st line setting, increased delivery of 2L-Ctx to patients with APC and maintained performance status may offer a survival benefit.

Multicenter phase II clinical trial of everolimus in Japanese patients with unresectable or metastatic renal cell carcinoma (mRCC) after failure of treatment with first-line tyrosine kinase inhibitor (TKI) therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 455-455
Author(s):  
Seiichiro Ozono ◽  
Masafumi Oyama ◽  
Masahiro Nozawa ◽  
Kiyohide Fujimoto ◽  
Ken Kishida ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Line Setting

455 Background: Everolimus has shown the efficacy and the safety in the phase III trial (RECORD-1) in patients with mRCC after failure of Vascular Endothelial Growth Factor Receptor-TKI. However, 26% of patients received two TKIs (sunitinib and sorafenib) as previous therapy in RECORD-1. In addition, as pre-treatment before TKI, 65% of patients received cytokine therapy and 13% of patients received chemotherapy. Therefore, there is still no clear evidence of everolimus as second line setting after failure of 1st-line TKI therapy. Methods: This study is an open-label, multi-center, single-arm, phase II trial. Primary endpoint is progression-free survival (PFS), and secondary endpoints are overall survival, objective response rate, time-to-treatment-failure, safety and quality of life (EORTC QLQ-C30, FKSI-DRS, EQ-5D). Key eligibility criteria are RCC with clear cell component, patients who received one TKI as first line therapy, patients who did not receive cytokine and chemotherapy and ECOG performance status 0-1. Results: 57 patients were enrolled from 02/11 to 12/12. Median age was 63 years, common sites of metastasis were lung (32.7%) and bone (12.2%), 79.6% had previous nephrectomy, previous TKI therapy were sunitinib (69.4%), sorafenib (22.4%) and axitinib (8.2%). Median PFS was 4.4 months (95% confidence interval: 3.7-6.0). 8.2% had partial response and 57.1% had stable disease according to RECIST v.1.0. The incidence of adverse events (AEs) of all grades was 95.9%. Major AEs were stomatitis (49.0%), hypertriglyceridemia (26.5%) and hypercholesterolemia (24.5%). Serious AEs were stomatitis (10.2%), interstitial lung disease (6.1%) and rash (6.1%). There were no treatment related deaths. All QOL scores were not changed at 2 months, while dyspnea and global health scores of EORTC QLQ-C30 and FKSI-DRS score were worsened at 4 months. Conclusions: This study is a first report of everolimus as second line setting after failure of 1st-line TKI. Further study and long-term follow-up would be warranted. Clinical trial information: UMIN000004742.

FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel: Results from the phase II RAMIRIS Study of the AIO.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4514-4514 ◽  
Author(s):  
Sylvie Lorenzen ◽  
Peter C. Thuss-Patience ◽  
Claudia Pauligk ◽  
Eray Goekkurt ◽  
Thomas Jens Ettrich ◽  
...  
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Response Rate ◽  
Objective Response ◽  
Disease Control Rate ◽  
Phase Iii ◽  
Response Analysis ◽  
Second Line ◽  
Significant Difference ◽  
Gastroesophageal Adenocarcinoma

4514 Background: Ramucirumab (Ram) as monotherapy or plus paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma (GEA). More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. These pts may benefit more from another, non-cross resistant chemotherapy backbone regimen. This trial evaluates the addition of Ram to FOLFIRI as second line treatment. Methods: This is a multicenter, randomized, investigator initiated, phase II trial. Pts with GEA who have progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomized 2:1 to either FOLFIRI plus Ram every two weeks (Arm A) or paclitaxel (days 1, 8, 15 of a 28-day cycle) plus Ram every two weeks (Arm B). Major endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and toxicity. Results: 111 pts (median age 61 years, 65% of pts had prior docetaxel therapy) were enrolled and 110 analyzed within intention to treat population (ITT, Arm A, 72; Arm B, 38). In the ITT, there was no significant difference in median OS (A, 6.8 vs. B, 7.6 months, HR 0.94, p = 0.77) and median PFS (A, 4.6 vs. B, 3.6 months, HR 0.72, p = 0.12). For pts with prior docetaxel use (71/110), median PFS was A, 4.3 vs. B, 2.0 months, HR 0.49, p = 0.008 and median OS was A, 7.5 vs. B, 6.4 months, HR 0.71, p = 0.25. In 101 pts with tumor assessment and included in the response analysis, ORR and DCR was 23% and 65% in Arm A and 11% and 60% in Arm B, respectively. 67 pts assessable for response were pre-treated with docetaxel. In these pts, ORR was 24% in Arm A and 9% in Arm B. Disease control rate (DCR) was 67% and 41% for Arm A and B respectively. Both therapies were similarly tolerable, final safety results will be shown. Conclusions: The RAMIRIS trial demonstrated feasibility of the combination of FOLFIRI and Ram. With a response rate of 24% and a median PFS of 4.3 months, docetaxel pre-treated pts seemed to derive pronounced benefit from FOLFIRI-Ram, providing a rationale for a phase III trial, which is currently ongoing. Clinical trial information: NCT03081143 .

A phase II trial combining tumor-targeting TP53 gene therapy with gemcitabine/nab-paclitaxel as a second-line treatment for metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4139-4139
Author(s):  
Chris Poki Leung ◽  
Minal A. Barve ◽  
Ming-Shiang Wu ◽  
Kathleen F. Pirollo ◽  
James F. Strauss ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Tp53 Gene ◽  
Phase Iii ◽  
Published Data ◽  
Line Treatment ◽  
Second Line ◽  
First Line

4139 Background: Nearly all stage IV pancreatic adenocarcinoma (PAC) patients progress after first-line treatment, and second-line options are limited. SGT-53 is an investigational product for tumor-targeted TP53 gene therapy that has completed phase Ia/Ib trials [Senser et al (2013), Mol Ther 21:1096; Pirollo et al (2016) Mol Ther 24:1697]. Methods: Here we provide an interim analysis of a Phase II trial (SGT53-02-1; NCT02340117) combining SGT-53 with gemcitabine/nab-paclitaxel (GEM/ABX). Eligible were first-line patients or those who had progressed after FOLFIRINOX (FFX) and/or gemcitabine-based therapy (second-line). In a 7-week treatment cycle, SGT-53 (3.6 mg DNA) was given once or twice weekly with GEM/ABX (1000 mg/m2/wk and 125 mg/m2/wk, respectively, for 3 of 4 weeks). Progression-free survival (PFS) and objective response rate (ORR) are primary endpoints.Overall survival (OS) and PFS are estimated by Kaplan-Meier analysis. Results: Of all evaluable patients (n=20), best response in 7 patients was determined to be partial response (PR) and 13 had stable disease (SD); none had progressive disease. In the second-line patients (n=11) there were 5 PR and 6 SD after 9 had failed FFX treatment, 3 had failed gemcitabine-based treatment and 1 had failed both. For patients with elevated CA19-9, SGT-53 + GEM/ABX resulted in marked reductions in the tumor marker. Published data for patients with PAC after therapy failure [Mita et al (2019) J Clin Med 8: 761; Portal et al (2015) Br J Cancer 113:989; Wang-Gillam et al (2016) Lancet 387:545] are shown for comparison. Notably, mPFS in our second-line patients was 7.4 months versus 3.1 months for the approved second-line therapy [Wang-Gillam et al (2016)]. This improvement in PFS exceeds the benchmark proposed to predict a clinically meaningful Phase III trial [Rahib et al (2016) Lancet Oncol 2:1209]. Conclusions: Our data suggest a clinically meaningful benefit of adding SGT-53 to GEM/ABX particularly for second-line PAC patients, most of whom had failed prior FFX treatment. Clinical trial information: NCT02340117. [Table: see text]

659 AN SINGLE-ARM OPEN-LABEL PHASE II STUDY OF CAMRELIZUMAB PLUS APATINIB AS SECOND-LINE TREATMENT FOR ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Qingxia Fan ◽  
Junsheng Wang ◽  
Tao Wu ◽  
Yonggui Hong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Squamous Cell ◽  
Objective Response ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line

Abstract   Esophageal squamous cell carcinoma (ESCC) as a common malignancy is prevalent in East Asia and in eastern and southern Africa. Although pembrolizumab, nivolumab and camrelizumab are respectively recommended as second-line treatment for advanced ESCC due to improved overall survival (OS), objective response rate (ORR) was modest. New effective treatments are needed. Hence, the study of camrelizumab plus apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC was performed. Methods This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg camrelizumab intravenously every 2 weeks and apatinib 250 mg orally once per day in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS. Results At data cutoff (Feb 28, 2021), 52 pts were enrolled, including 42 males and 50 with distant metastases, with the median age of 62 years. In the evaluable population of 39 pts, ORR without confirmation was 43.59% and DCR was 94.87%. The median duration of response was 6.9 months (95% CI 4.57–9.23). The median PFS was 6.8 month (95% CI 2.66–10.94). The 12-month overall survival was 52.2%. A total of 80.8% of pts had treatment-related AEs (TRAEs) with 46.2% of grade ≥ 3 TRAEs. The safety profile of camrelizumab and apatinib was consistent with other anti–PD-1 antibodies and angiogenesis inhibitors. Conclusion This is the first study that evaluates the combination anti–PD-1 antibody and anti-angiogenesis inhibitor as a second-line therapy for advanced ESCC. Camrelizumab plus apatinib showed encouraging clinical efficacy and acceptable safety. Further phase III randomized trials are warranted.

scholarly journals HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: a multicenter, single-arm phase II trial

2020 ◽  
Vol 8 (2) ◽  
pp. e001279
Author(s):  
Yan Song ◽  
Ning Li ◽  
Qun Li ◽  
Xinjun Liang ◽  
Shu Zhang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Open Label ◽  
Gastroesophageal Junction Cancer

BackgroundIrinotecan is used as second-line treatment in advanced gastric or gastroesophageal junction (G/GEJ) cancer. The role of anti-programmed death-1 (PD-1) antibody plus irinotecan, in this setting and population is unclear.MethodsThis multicenter, open-label, single-arm, phase II trial was conducted in 11 Chinese hospitals. Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to, or intolerant of, first-line chemotherapy with a platinum and/or fluoropyrimidine. Subjects received HX008 200 mg intravenously every 3 weeks plus irinotecan 160 mg/m2 intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) as assessed according to Response Evaluation Criteria In Solid Tumors V.1.1.ResultsBetween October 2018 and September 2019, a total of 58 patients with advanced G/GEJ cancer were enrolled in this study. Median follow-up was 10.5 months (range 7.4–18.9) months. Confirmed ORR was observed in 16 patients, for an ORR of 27.6% (95% CI 16.1% to 39.1%); 19 patients experienced stable disease, leading to a disease control rate of 60.3% (95% CI 46.4% to 73.0%). ORR in patients with PD-ligand 1 (L1) positive (Combined Positive Score (CPS) ≥1) and negative (CPS＜1) tumors was 38.5% (5/13) and 37.5% (3/8), respectively. Median duration of response was 8.0 months (range 1.5–12.5), 6 of 16 (37.5%) responses were ongoing. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2 to 5.5). Median overall survival (OS) was not reached (NR) (95% CI 8.7 to NR). Patients with PD-L1 positive tumors tended to have longer OS than those with PD-L1 negative tumors, but the difference was not statistically significant (NR vs 8.7 months, p=0.1858).The most common treatment-related adverse events of grade 3 or 4 included neutropenia (32.8%), leukopenia (31.0%), anemia (17.2%), decreased appetite (8.6%), vomit (6.9%), nausea (6.9%) and fatigue (5.2%). There were no treatment-related deaths.ConclusionThe combination of HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer, which warrants further study.Trial registration numberNCT03704246

A randomized, double-blind, placebo-controlled phase III study of cisplatin plus a fluoropyrimidine with or without ramucirumab as first-line therapy in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (RAINFALL, NCT02314117).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS178-TPS178 ◽  
Author(s):  
Charles S. Fuchs ◽  
Josep Tabernero ◽  
Salah-Eddin Al-Batran ◽  
Ian Chau ◽  
David H. Ilson ◽  
...  
Keyword(s):  
Disease Progression ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Safety Analysis ◽  
Phase Iii ◽  
Population Pharmacokinetic ◽  
Type I ◽  
Line Treatment ◽  
First Line ◽  
Double Blind

TPS178 Background: Ramucirumab, a human IgG1 monoclonal antibody directed to the ectodomain of VEGFR-2, prevents ligand binding to the receptor, blocking activation of downstream receptor-mediated pathways. Ramucirumab has demonstrated significant improvement in overall survival (OS) and progression-free survival (PFS) in 2 phase III registration studies (REGARD, RAINBOW) in patients in second-line treatment of gastric cancer. This global phase III trial will compare PFS in patients with HER2-negative, metastatic gastric or GEJ adenocarcinoma receiving ramucirumab with cisplatin/capecitabine (or 5-FU) versus placebo with cisplatin/capecitabine (or 5-FU) as first-line treatment. The trial is conducted in 137 sites in the Americas, Europe and Japan and is currently open to enrollment. Methods: Eligible patients will be randomized to receive ramucirumab (8mg/kg on days 1 and 8, based upon population pharmacokinetic modelling) or placebo with cisplatin/capecitabine every 21-day cycle until disease progression, unacceptable toxicity, or other withdrawal criteria are met. The primary endpoint is PFS; OS is the key secondary endpoint. Efficacy will be considered at 3 analysis points: futility analysis for PFS, primary analysis of PFS & final analysis of OS. A gatekeeping strategy will be used to assess PFS and OS. The OS endpoint will only be tested if the PFS test is significant to control Type I error at 5% across both endpoints. An exposure/safety analysis will be done after 60 patients have started the 3rd cycle. The study has 90% power to demonstrate a PFS advantage assuming HR = 0.70 and 80% power to demonstrate an OS advantage assuming HR = 0.77. Other secondary endpoints include PFS2 (the time from randomization to disease progression after the start of additional systemic anticancer treatment, or death from any cause, whichever occurs first), objective response rate, safety and quality of life. As of 9/11/2015, 128 patients have been enrolled in 19 countries. The 1st exposure/safety analysis is underway. Clinical trial information: NCT02314117.

scholarly journals How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1189 ◽  
Author(s):  
Galvano ◽  
Incorvaia ◽  
Badalamenti ◽  
Rizzo ◽  
Guarini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Phase Iii ◽  
Second Line ◽  
Anti Vegf ◽  
Significant Difference ◽  
Line Setting ◽  
The Impact

Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and G3-G5 toxicities. Our results showed significantly improved OS (HR 0.83, 95% CI 0.72–0.94) and DCR (HR 1.27, 95% CI 1.04–1.54) favouring anti-VEGF combinations in overall population; no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95% CI 0.70–1.09). Anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95% CI 0.31–0.96), showing a trend also in all RAS wt patients (RR 0.63, 95% CI 0.48–0.83). No significant difference in PFS and DCR all RAS was registered. Our results provided for the first time a strong rationale to manage both targeted agents in second line setting.

Tremelimumab in combination with durvalumab in first or second-line mesothelioma patients: Safety analysis from the phase II NIBIT-MESO-1 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8558-8558 ◽  
Author(s):  
Luana Calabro ◽  
Aldo Morra ◽  
Diana Giannarelli ◽  
Giovanni Amato ◽  
Erica Bertocci ◽  
...  
Keyword(s):  
Phase Ii ◽  
Liver Toxicity ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Safety Analysis ◽  
Primary Objective ◽  
Second Line ◽  
Open Label ◽  
Ecog Performance Status

8558 Background: The anti-CTLA-4 tremelimumab at two different dose-schedules of administration showed promising activity in second-line malignant mesothelioma (MM) patients (Calabrò et al., Lancet Oncol, 2013; Calabrò et al., Lancet Respir Med, 2015). These initial results and the efficacy of targeting the PD-1/PD-L1 axis in different tumor types, prompted the NIBIT-MESO-1 study aimed at investigating the efficacy and safety of tremelimumab combined with the anti-PD-L1 durvalumab in mm patients. We report the safety analysis from the fully-enrolled NIBIT-MESO-1 study. Methods: The NIBIT-MESO-1 is a phase II, open-label, single Center study. Forty mm patients received tremelimumab at 1 mg/Kg i.v. every 4 weeks (Q4W) for 4 doses, and durvalumab at 20 mg/Kg i.v. Q4W for 13 doses. Primary objective is immune-related (ir)-objective response rate; secondary are safey, ir-disease control rate, ir-progression free survival, and overall survival. Tumor assessment per ir-modified RECIST or ir-RECIST 1.1 for pleural or peritoneal MM, respectively, was performed at baseline and q12 weeks. Adverse events (AEs) were recorded according to CTC v4.0. (ClinicalTrials.gov Id: NCT02588131). Results: From October 2015 to October 2016, 40 mm patients (38 pleural and 2 peritoneal), median age 64 years (range 41-80), ECOG performance status 0 (n = 19) or 1 (n = 21) were enrolled in the study. mm histology was epithelioid (n = 32), biphasic (n = 5), sarcomatoid (n = 2) or undefined (n = 1). As of January 2017, 12 first or 28 second-line mm patients received a median of 5.5 doses of therapy (range = 1-13). Twenty-four patients (60%) experienced any grade irAEs: 5 patients (12.5%) had grade 3-4 AEs, the most frequent being hepatotoxicity (7.5%). AEs were generally manageable and reversible per protocol guidelines. Three patients (7.5%) were discontinued due to treatment-related AEs (1 trombocytopenia, 1 limbic encephalitis, 1 liver toxicity). Conclusions: The combination of tremelimumab and durvalumab is safe and manageable in mm patients. Clinical trial information: NCT02588131.

Ipilimumab (Ipi) retreatment at 10 mg/kg in patients with metastatic melanoma previously treated in phase II trials.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9059-9059 ◽  
Author(s):  
Bart Neyns ◽  
Jeffrey S. Weber ◽  
Celeste Lebbé ◽  
Michele Maio ◽  
Kaan Harmankaya ◽  
...  
Keyword(s):  
Phase Ii ◽  
Safety Profile ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Primary Objective ◽  
Small Sample ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Study Results

9059 Background: Ipi is a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte antigen-4 to augment antitumor immune responses. In phase III study MDX010-20, where patients (pts) could be retreated if they met safety criteria and achieved an objective response or stable disease ≥3 months from the end of the induction period (q3 weeks for 4 doses), 21 of 31 pts (68%) retreated with Ipi reestablished disease control. CA184-025 is a roll-over study of extended Ipi treatment or survival follow-up in pts who received Ipi in phase II trials, with the primary objective of evaluating safety during extended treatment. We report the safety profile in pts retreated with Ipi in study 025. Methods: Eligible pts in phase II trials CA184-004, -007, -008, -022, MDX010-08, or -015 were enrolled in study 025 (N=248) to receive retreatment (at the time of progression), extended maintenance (if no prior progression), or survival follow-up only. Pts were ineligible for retreatment if they had experienced a grade 3-4 non-skin toxicity during prior Ipi therapy. Ipi was administered at 10 mg/kg, q3 weeks for 4 doses, to 111 pts who initially received Ipi induction at 0.3, 3, or 10 mg/kg in a parent study. Results: In this selected population of eligible pts, the nature and frequency of immune-related adverse events (irAEs) during retreatment were similar to those reported in previous studies, which most commonly affected the GI tract and skin (Table). There were no new types of drug-related irAEs and no grade 5 irAEs upon retreatment. Conclusions: Retreatment with Ipi at 10 mg/kg in these pts was generally well tolerated and the safety profile was similar to that during induction dosing in the parent studies. The higher frequencies of irAEs at lower doses should be interpreted with caution given the small sample sizes. An ongoing, randomized phase II trial will evaluate the clinical benefit of Ipi retreatment. Clinical trial information: NCT00162123. [Table: see text]

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