scholarly journals A randomized phase II trial of efficacy and safety of the immunotherapy ALECSAT as an adjunct to radiotherapy and temozolomide for newly diagnosed glioblastoma

2021 ◽  
Author(s):  
Katja Werlenius ◽  
Giuseppe Stragliotto ◽  
Michael Strandeus ◽  
Malin Blomstrand ◽  
Helena Carén ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Open Label ◽  
Serious Adverse Events ◽  
Significant Difference

Abstract Background There is an urgent need for effective treatments against glioblastoma (GBM). In this trial we investigated the efficacy and safety of an adoptive cell-based immunotherapy. Methods Patients with newly diagnosed GBM were recruited at four study sites in Sweden. The patients were randomized 1:2 to receive either radiotherapy (RT), 60 Gy/30 fractions, with concomitant and adjuvant temozolomide (TMZ) only, or RT and TMZ with addition of Autologous Lymphoid Effector Cells Specific Against Tumor (ALECSAT) in an open-label phase II trial. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were survival and safety of ALECSAT. Results Sixty-two patients were randomized to either RT and TMZ alone (n=22) or RT and TMZ with ALECSAT (n=40). Median age was 57 years (range 38-69), 95% of the patients were in good performance status (WHO 0-1). There was no significant difference between the study arms (SOC vs. ALECSAT + SOC) in PFS (7.9 vs. 7.8 months; HR 1.28; 95% CI 0.70, 2.36; P=0.42), or in median overall survival (OS) (18.3 vs. 19.2 months; HR 1.16, 95% CI 0.58, 2.31; P=0.67). The treatment groups were balanced in terms of serious adverse events (52.4% vs. 52.5%), but adverse events ≥ grade 3 were more common in the experimental arm (81.0% vs. 92.5%). Conclusion Addition of ALECSAT immunotherapy to standard treatment with radiochemotherapy was well tolerated but did not improve PFS or OS for patients with newly diagnosed GBM.

scholarly journals Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation

2020 ◽  
Vol 38 (13) ◽  
pp. 1378-1388 ◽  
Author(s):  
Eileen M. O’Reilly ◽  
Jonathan W. Lee ◽  
Mark Zalupski ◽  
Marinela Capanu ◽  
Jennifer Park ◽  
...  
Keyword(s):  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
High Response Rate ◽  
Open Label ◽  
Free Survival ◽  
Palb2 Mutation

PURPOSE Five percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (g BRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in g BRCA/PALB2+ PDAC. PATIENTS AND METHODS Eligible patients had untreated g BRCA/PALB2+ PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses. RESULTS Fifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B ( P = .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B ( P = .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months; P = .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months; P = .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia. CONCLUSION Cisplatin and gemcitabine is an effective regimen in advanced g BRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in g BRCA/ PALB2+ PDAC.

A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4566-4566
Author(s):  
S. Sym ◽  
S. Park ◽  
J. Park ◽  
K. Kwon ◽  
I. Jung ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tolerability Profile ◽  
Preliminary Results ◽  
Weekly Docetaxel ◽  
Randomized Phase Ii ◽  
Significant Difference

4566 Background: Docetaxel, in combination with cisplatin or oxaliplatin, has demonstrated efficacy against AGC. This randomized phase II trial evaluated two weekly docetaxel-based regimens to see which would be most promising according to objective response rate (ORR) as first-line therapy in AGC. Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric adenocarcinoma and a performance status ≤2 were randomly assigned to receive docetaxel (35 mg/m2) weekly on days 1 and 8 of a 21-day cycle plus either cisplatin (60 mg/m2 on day 1) (arm A) or oxaliplatin (120 mg/m2 on day 1) (arm B). Toxicity was assessed on days 1, 8, and 21 of each cycle, and response was evaluated every 2 cycles. Results: Between March 2007 and December 2008, 61 eligible patients entered. In Arm A, 29 patients were evaluable for objective response and 31 for safety. In Arm B, 28 patients were evaluable for objective response and 30 for safety. Median age was 52 years and disease status was comparable for both arms. Ten of 29 (34.5%) patients had a confirmed objective response in the arm A (95% confidence interval [CI] 17.1–51.8%) and 11 of 28 (39.2%) patients had a confirmed objective response in the arm B (95% CI 21.1- 57.2%). No significant difference was noted between the arms both for ORR (p=0.202) or for disease control (58.6% and 82.1%, respectively, p=0.082). Median progression free survival time was 4.4 month in the arm A and 4.3 months in the arm B (Hazard ratio = 0.936; 95% CI, 0.503–1.744; p = 0.836). There was no relevant difference in the occurrence of overall grade ¾ toxicity between the two arms (51.6% vs. 46.6%, respectively; p=0.800). Neutropenia was the most common grade 3/4 toxicity (32.3% vs. 36.6%, respectively). There was one treatment related death in Arm B. Conclusions: The preliminary results showed that both treatment arms have similar clinical efficacy as front-line treatment in AGC. Each regimen has a manageable tolerability profile. The accrual is ongoing. No significant financial relationships to disclose.

Interim safety analysis of the DANTE trial: Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma—A randomized, open-label phase II trial of the German Gastric Group at the AIO and SAKK.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4549-4549
Author(s):  
Nils Homann ◽  
Sylvie Lorenzen ◽  
Michael Schenk ◽  
Peter C. Thuss-Patience ◽  
Eray Goekkurt ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Safety Analysis ◽  
Open Label ◽  
Serious Adverse Events ◽  
Open Label Phase

4549 Background: The DANTE study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with perioperative FLOT. Here, we report the protocol-defined interim safety analysis. Methods: DANTE is a multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients (pts) with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Pts are randomized 1:1 to 4 pre-operative 2-week cycles of FLOT followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS). Results: Recruitment started in Sep 2018; by Feb 2020, a total of 175 pts have been randomized. This analysis is based on the first 40 pts (20 pts in each arm). The pts had a median age of 62 y and 75% of pts had an ECOG PS of 0 in both arms. The cohort was well balanced in terms of tumor location and clinical stage. 5% of the 40 patients (overall 7.4% of 175 pts enrolled) showed microsatellite instability. 90% of pts enrolled completed all pre-operative cycles in each arm. Total number of adverse events with relation to study treatment was 154 in arm A and 148 in arm B. Total number of serious adverse events (SAE; related or not) was 16 in Arm A and 14 in arm B. 20% of pts in each arm had an SAE due to perioperative morbidity. No surgical mortality was observed. 18 and 19 pts proceeded to operation in arms A and B, respectively. Premature treatment discontinuation occurred in 2 pts in each arm: disease progression (1) and deterioration of general health condition (1) in arm A; and pts’ wish (1) and death (1) in arm B. Median hospitalization time was 15 days in arm A and 16 days in arm B. Conclusions: Perioperative atezolizumab plus FLOT is feasible and safe. The study continues recruitment. Clinical trial information: NCT03421288 .

scholarly journals ACTR-69. FEASIBILITY STUDY OF THE EMULATE THERAPEUTICS™ VOYAGER SYSTEM IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi29-vi29
Author(s):  
Garni Barkhoudarian ◽  
Nicholas Blondin ◽  
Sajeel Chowdhary ◽  
Ekokobe Fonkem ◽  
Brian Vaillant ◽  
...  
Keyword(s):  
Adverse Events ◽  
Outcome Measure ◽  
Progression Free Survival ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Secondary Outcome Measure ◽  
Newly Diagnosed ◽  
Open Label ◽  
Serious Adverse Events ◽  
Radio Frequency Energy

Abstract BACKGROUND The EMulate Therapeutics Voyager system is an investigational non-sterile, non-invasive, non-thermal, non-ionizing, portable, home-use medical device that uses a specific, localized ultra-low radio frequency energy (ulRFE®) cognate for the treatment of brain cancer. METHODS This open-label, multi-center study (NAT-109) enrolled adults newly diagnosed with GBM. Following surgical debulking, patients were enrolled and treated concurrently with temozolomide, radiotherapy, and Voyager. The objective of the study is to assess if the Voyager is a safe and feasible treatment for newly diagnosed GBM when combined with standard of care. The primary outcome measure is safety, assessed by the incidence and evaluation of any adverse events (AEs) associated with the Voyager. The secondary outcome measure is clinical utility, assessed by progression-free survival and overall survival. RESULTS Enrollment is closed, and treatment and long-term follow-up is ongoing. A total of 37 patients were enrolled and treated. 27 patients reported 282 AEs, none of which required withdrawal from the study. One AE was reported as probably related to the device - i.e., mild dysesthesia, which resolved without interruption or cessation of treatment with the device. 15 patients reported 28 SAEs, and none were reported as related to the device. 56% of patients were progression-free at 6 months, and 43% were progression-free at 12 months. 89% of patients were still alive after 6 months, 71% were still alive after 12 months. CONCLUSIONS The Voyager system appears to be safe and feasible for the treatment of newly diagnosed GBM. Given that therapy is delivered non-invasively and no device-related serious adverse events were reported, further prospective study of the investigational device is planned.

Phase II study to evaluate efficacy and safety of irinotecan, capecitabine, and bevacizumab in metastatic colorectal cancer (mCRC) patients.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 501-501 ◽  
Author(s):  
Pilar Garcia Alfonso ◽  
Manuel Chaves-Conde ◽  
Andres Munoz ◽  
Antonia Salud ◽  
Carlos Garcia-Giron ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Efficacy And Safety ◽  
Open Label ◽  
Ecog Performance Status ◽  
Combination Methods ◽  
Kras Status

501 Background: XELIRI regimen biweekly (combination of capecitabine and irinotecan) is an active and well tolerated treatment for mCRC. Bevacizumab provides significant clinical benefits in previously treated patients with mCRC. On this basis, the aim of this study is to evaluate the efficacy and safety of this combination. Methods: Multicentric, prospective, open-label phase II trial. Treatment scheme: irinotecan (iri) (175mg/m2 d1 q2w) + capecitabine (xel)(1,000mg/m2bid d 2-8) + bevacizumab (bev) (5mg/kg, d1 q2w). Results: 77 patients (p) were evaluated (66.2%, male) with a median age of 65.1 years (41.1-81.1). ECOG performance status was ≤1 in 96.1%. Primary tumor locations were: colon (53.2%), rectum (31.2%), and rectum/colon (15.6%). 27 p (35.1%) received adjuvant chemotherapy. Metastases were detected in liver (62.3%) and lung (54.5%). Mean time in treatment was: 7.1±4.9 months and median of cycles administered was 12(1-43). Median relative dose intensity was 89% for xel and bev and 85% for iri. Best response confirmed were: complete response (5.2%), partial response (32.5%), stable disease (46.8%). After a median of follow-up of 23.3 (0.4-39.6) months, median overall survival (OS) and progression free survival (PFS) was 24.8 and 11.8 months respectively. Analysis on Kras status was done in 71 p. There were no significant differences in OS or in PFS between WT and MUT p. 17 p (22.1%) underwent salvage surgery, 12 of whom had an R0 resection. The most frequent G3-4 toxicities were: diarrhea (18.2%), asthenia (16.9%), pulmonary embolism (13%; in eight of 10 p were asymptomatic), neutropenia (10.4%), febrile neutropenia (6.5%) and HFS (5.2%). Three treatment related deaths were reported (2 cases of multi-organ failure, and 1 case of intestinal perforation). Conclusions: Bevacizumab combined with biweekly XELIRI is an active first-line regimen for mCRC treatment with a feasible and manageable safety profile. Bevacizumab treatment efficacy was independent on Kras status. Clinical trial information: NCT00875771. [Table: see text]

RAINIER: A randomized, double-blinded, placebo-controlled phase II trial of gemcitabine (gem) plus nab-paclitaxel (nab-P) combined with apatorsen (A) or placebo (Pl) in patients (pts) with metastatic pancreatic cancer (mPC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 419-419 ◽  
Author(s):  
Andrew H. Ko ◽  
Patrick B. Murphy ◽  
James D. Peyton ◽  
Dianna Shipley ◽  
Ahmed Al-Hazzouri ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Experimental Treatment ◽  
Progression Free Survival ◽  
Serious Adverse Events ◽  
Secondary Endpoints ◽  
Tumor Growth And Metastasis ◽  
Double Blinded

419 Background: Heat shock protein 27 (Hsp27) is over-expressed in PC, enabling tumor growth and metastasis. A is an antisense oligonucleotide that binds to Hsp27 mRNA and inhibits production of Hsp27 protein. This randomized phase II trial evaluates the efficacy of gem/nab-P plus A or Pl in pts with mPC. Methods: Pts with untreated mPC were randomized 1:1 to Arm A (gem, nab-P, A) or Arm B (gem, nab-P, Pl). 3 loading doses of 600mg A IV or Pl IV were given, then 600 mg A or Pl weekly with chemotherapy in 28 day cycles. Both arms received gem 1000mg/m2 IV, nab-P 125mg/m2 IV days 1, 8, and 15. Restaging was every 2 cycles. Serum Hsp27 levels were collected at baseline and on treatment. Primary endpoint compared overall survival (OS); secondary endpoints were progression free survival (PFS), response rate (RR), CA 19-9 response, and toxicity. Results: 132 pts were randomized: median age 66 yrs, 57% male, 47% ECOG 0. Demographics were similar for both arms. 36% of pts on Arm A and 48% of pts Arm B discontinued due to progressive disease, and 24% and 14% due to adverse events (AEs). There was a higher incidence of ≥Grade (G) 4 and serious adverse events (SAEs) in Arm A. The most frequently reported G 3/4 treatment-related AEs were anemia (20%), neutropenia (17%), and fatigue (16%) on Arm A and anemia (27%), neutropenia (19%), and thrombocytopenia (13%) on Arm B. Overall RR was 18% on each arm. With a median f/u of 9.1 mos, median PFS and OS are 2.7 and 5.2 mos on Arm A and 3.8 and 6.9 mos on Arm B (p=NS). Correlative analyses between Hsp27 expression and clinical outcomes will be presented. In a statistical model using only Arm B data, 3 base attributes, ECOG >0, liver mets, and neutrophil levels had a strong prognostic relationship to OS. Conclusions: This study showed no improvement in clinical outcomes adding A to gem plus nab-p. G 4 AEs and SAEs were increased with A. We await analysis for Hsp 27 and CA 19-9 levels and further analysis to identify any pt subgroup who might have benefited from the experimental treatment. Clinical trial information: NCT01844817.

Phase II trial of bevacizumab and temozolomide for upfront treatment of elderly patients with newly diagnosed glioblastoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2012-2012
Author(s):  
Phioanh Leia Nghiemphu ◽  
Hye Hyun Bahng ◽  
Albert Lai ◽  
Nadia Faiq ◽  
William H. Yong ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Adverse Events ◽  
Elderly Patients ◽  
Tumor Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Safety And Efficacy

2012 Background: Randomized clinical trials in newly diagnosed, elderly GBM patients have shown that treatment with temozolomide chemotherapy is at least equivalent to treatment with radiotherapy. Glioblastoma in elderly patients may also have high angiogenic activities. Bevacizumab is an antiangiogenic agent, a humanized monoclonal antibody directed against the vascular endothelial growth factor. We conduct a clinical trial of temozolomide and bevacizumab to evaluate the safety and efficacy of this combination in the treatment of elderly patients with newly diagnosed GBM, good performance status, and willing to forgo upfront treatment with radiation therapy. Methods: This is a phase II trial of newly diagnosed GBM patients age ≥70 with no prior treatments other than surgery and Karnofsky Performance Status (KPS) ≥60. Patients receive treatments 4-6 weeks after surgery with bevacizumab (10mg/kg every 2 weeks) and temozolomide (150-200 mg/m2 for 5 days out of 28 days, up to 12 cycles) until tumor progression. Primary outcome measures are overall survival and safety evaluations. Results: From June 2010 to January 2016, 50 GBM patients enrolled in this study. To date, all patients have tumor progression and 3 are still alive. The median age is 75 (range 70 - 87), and median KPS is 80 (range 60-100). 15 patients have a gross total resection. 26 out of 49 patients with tissues available for evaluation have methylation of the MGMT promoter, and no patient has IDH-1 mutation. Median overall survival is 12.3 months (14.8 months for those with methylation of MGMT, 10.0 months for unmethylated MGMT). Serious adverse events related to treatments include wound healing problems (2), CNS hemorrhage (3), pulmonary embolism (4), and bowel perforation (1). Serious hematological adverse events include thrombocytopenia (3) and neutropenia (5). Conclusions: For patients with newly diagnosed GBM age ≥70, KPS ≥60, treatment with temozolomide and bevacizumab may show promising survival benefits and have tolerable side effects. More detailed safety and efficacy analysis will be presented. Clinical trial information: NCT01149850.

Safety of perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: An interim safety analysis of the DANTE, a randomized, open-label phase II trial of the German Gastric Group at the AIO and the SAKK.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 398-398
Author(s):  
Salah-Eddin Al-Batran ◽  
Sylvie Lorenzen ◽  
Michael Schenk ◽  
Peter C. Thuss-Patience ◽  
Eray Goekkurt ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Safety Analysis ◽  
Open Label ◽  
Serious Adverse Events ◽  
Open Label Phase

398 Background: The DANTE study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with perioperative FLOT. Here, we report the protocol-defined interim safety analysis. Methods: DANTE is a large, multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients (pts) with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Pts are randomized 1:1 to 4 pre-operative 2-week cycles (8 weeks) of FLOT followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS). Results: Recruitment started in Sept 2018; by September 2019, a total of 122 pts have been randomized. This analysis is based on the first 40 pts (20 pts in each arm). The pts had a median age of 62 y and 75% of pts had an ECOG PS of 0 in both arms. The cohort was well balanced in terms of tumor location and clinical stage. 90% of pts enrolled completed all pre-operative cycles in each arm. Total number of adverse events with relation to study treatment was 154 in arm A and 148 in arm B. Total number of serious adverse events (SAE; related or not) was 16 in Arm A and 14 in arm B. 20% of pts in each arm had an SAE due to perioperative morbidity. No surgical mortality was observed. 18 and 19 pts proceeded to operation in arms A and B, respectively. Premature treatment discontinuation occurred in 2 pts in each arm: disease progression (1) and deterioration of general health condition (1) in arm A; and pts’ wish (1) and death (1) in arm B. Median hospitalization time was 15 days in arm A and 16 days in arm B. Conclusions: perioperative atezolizumab plus FLOT is feasible and safe. The study continued recruitment. Clinical trial information: NCT03421288.

scholarly journals An open-label, single-arm, phase II trial of buparlisib in patients with melanoma brain metastases not eligible for surgery or radiosurgery—the BUMPER study

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Teresa Amaral ◽  
Heike Niessner ◽  
Tobias Sinnberg ◽  
Ioannis Thomas ◽  
Andreas Meiwes ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Pi3k Inhibitor ◽  
Open Label ◽  
Preclinical Data ◽  
Overall Response ◽  
Intracranial Disease ◽  
Dismal Prognosis

Abstract Background Patients with melanoma brain metastasis (MBM) still carry a dismal prognosis. Preclinical data originated in xenograft models showed that buparlisib therapy was highly effective in therapy-naïve MBM. Patients and Methods In this open-label, phase II trial, we investigate the safety and efficacy of monotherapy with buparlisib, a PI3K inhibitor, in patients with asymptomatic MBM who were not candidates for local therapy. These patients had also progressed under immunotherapy if BRAF wild-type or under targeted therapy with BRAF/MEK inhibitors if carrying a BRAFV600E/K mutation. The primary endpoint was the intracranial disease control rate assessed by the investigators. The secondary endpoints were overall response rate, duration of response (DOR) of intracranial disease, overall response, progression-free survival (PFS), overall survival (OS), safety, and tolerability of buparlisib. Results A total of 20 patients were screened and 17 patients were treated with buparlisib. Twelve patients had progressed under more than 2 systemic therapy lines and 17 had received at least 1 previous local therapy. There were no intracranial responses. Three patients achieved intracranial stable disease; the median DOR was 117 days. The median PFS was 42 days (95% confidence interval [CI]: 23–61 days) and the median OS was 5.0 months (95% CI: 2.24–7.76 months). No new safety signs were observed. Conclusions Buparlisib was well tolerated but no intracranial responses were observed. These results might be explained in part by the inclusion of only heavily pretreated patients. However, preclinical data strongly support the rationale to explore PI3K inhibitor-based combinations in patients with MBM displaying hyperactivation of the PI3K–AKT pathway.

scholarly journals POS0630 COMPARISON OF THE EFFICACY AND SAFETY OF ORIGINAL AND BIOSIMILAR ADALIMUMAB MOLECULES IN CHILDHOOD RHEUMATIC DISEASES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 553.1-553
Author(s):  
K. Ulu ◽  
F. Demir ◽  
T. Coşkuner ◽  
Ş. Çağlayan ◽  
B. Sözeri
Keyword(s):  
Adverse Events ◽  
Disease Activity ◽  
Rheumatic Diseases ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Inactive Disease ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Significant Difference ◽  
Abp 501

Background:The TNF-α inhibitor adalimumab is a biological disease modifying anti-rheumatic drug (bDMARD) that has been used in different rheumatic diseases with a resistant course. ABP-501 is a biosimilar product (BP) of adalimumab, recently approved by the FDA and EMA. To our knowledge, there is no study assess the efficacy and safety of these two molecules on pediatric patients.Objectives:We aimed to compare the efficacy and safety of the original and biosimilar adalimumab (ABP-501) molecules in childhood rheumatic diseases.Methods:This non-interventional, retrospective, single-centre analysis carried out in Umraniye Training and Resrach Hospital, Pediatric Rheumatology Clinic, Istanbul, Turkey. The study group consisted of patients who were followed due to chronic rheumatic disease between January 1, 2016 and June 1, 2020, and received reference or biosimilar adalimumab therapy for at least three months. Demographic and clinical data of patients were collected at baseline, 3rd, 6th, and 12th months of treatment. Disease activity assessment was made with JADAS-27 in JIA patients, with SUN criteria in uveitis patients, and with Behçet’s Disease Activity Index in BD patients. Efficacy and safety of treatments were compared between reference and biosimilar adalimumab groups.Results:A total of 89 patients (65 with original and 24 with biosimilar molecule) treated with adalimumab, were included in the study. There were 45 female and 44 male in the study, and the median age at the initiation of the adalimumab was 166 months (min-max: 36-231). Of the 89 patients evaluated, the primary diagnoses of 62 were juvenile idiopathic arthritis, 13 were idiopathic uveitis, eight were Behçet’s disease, three were Blau syndrome, two were chronic recurrent multifocal osteomyelitis and one was Vogt-Koyanagi-Harada syndrome. 63 of the patients were biologic-naïve, and 13 were switched from etanercept, 11 from infliximab, and two from other bDMARDs. The median exposure time of adalimumab was 16 months (min-max:3-70) in RP and 14.5 months (min-max: 3-23) in BP. All patients had active disease before treatment. In the group treated with RP, inactive disease was achieved in 60%, 76.6% and 87.2% of the patients at the 3rd, 6th and 12th months, respectively. Also, inactive disease was achieved in 62.5%, 78.2% and 78.2% of the patients at the 3rd, 6th and 12th months in the group treated with BP, respectively. There was no statistically significant difference in efficacy between the groups at the 3rd, 6th and 12th months (p=0.83, 0.07 and 0.32). Serious adverse events were seen in one patient in each groups (lymphoma in RP group, tuberculous meningitis in BP group). Non-serious adverse events were observed in eight patients (12.3%) in the RP group and in two patients (8.3%) in the BP group, without statistically significant difference between groups (p=0.86).Conclusion:No significant difference was observed between the biosimilar adalimumab ABP-501 and RP adalimumab in terms of efficacy and safety.References:[1]Renton, William D et al. Pediatr Rheumatol Online J. 2019;17(1):67.[2]Lovell DJ, Ruperto N, Goodman S, et al. N Engl J Med. 2008;359(8):810-820.[3]Kingsbury, Daniel J et al. Clin Rheumatol 2014;33(10):1433-41.Disclosure of Interests:None declared

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