Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Phase 2 Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma

ABSTRACT: A Phase 2 Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma

PROVIDER: PRJNA773418 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

A Phase 2 Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma

Project description:In a post-hoc exploratory analysis of the KING trial to seek molecular markers of outcome, RNAseq was performed on resected tumor specimens at the time of diagnostic surgery before the recurrence from 57 study patients from all arms with adequate selinexor exposure and evidence of either clinical benefit or resistance defined above. RNAseq data were used to infer the activity for 6,203 master regulator proteins using the VIPER algorithm.

2021-12-01 | GSE186332 | GEO

A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma.

Project description:PurposeSelinexor is an oral selective inhibitor of exportin-1 (XPO1) with efficacy in various solid and hematologic tumors. We assessed intratumoral penetration, safety, and efficacy of selinexor monotherapy for recurrent glioblastoma.Patients and methodsSeventy-six adults with Karnofsky Performance Status ≥ 60 were enrolled. Patients undergoing cytoreductive surgery received up to three selinexor doses (twice weekly) preoperatively (Arm A; n = 8 patients). Patients not undergoing surgery received 50 mg/m2 (Arm B, n = 24), or 60 mg (Arm C, n = 14) twice weekly, or 80 mg once weekly (Arm D; n = 30). Primary endpoint was 6-month progression-free survival rate (PFS6).ResultsMedian selinexor concentrations in resected tumors from patients receiving presurgical selinexor was 105.4 nmol/L (range 39.7-291 nmol/L). In Arms B, C, and D, respectively, the PFS6 was 10% [95% confidence interval (CI), 2.79-35.9], 7.7% (95% CI, 1.17-50.6), and 17% (95% CI, 7.78-38.3). Measurable reduction in tumor size was observed in 19 (28%) and RANO-response rate overall was 8.8% [Arm B, 8.3% (95% CI, 1.0-27.0); C: 7.7% (95% CI, 0.2-36.0); D: 10% (95% CI, 2.1-26.5)], with one complete and two durable partial responses in Arm D. Serious adverse events (AEs) occurred in 26 (34%) patients; 1 (1.3%) was fatal. The most common treatment-related AEs were fatigue (61%), nausea (59%), decreased appetite (43%), and thrombocytopenia (43%), and were manageable by supportive care and dose modification. Molecular studies identified a signature predictive of response (AUC = 0.88).ConclusionsAt 80 mg weekly, single-agent selinexor induced responses and clinically relevant PFS6 with manageable side effects requiring dose reductions. Ongoing trials are evaluating safety and efficacy of selinexor in combination with other therapies for newly diagnosed or recurrent glioblastoma.

| S-EPMC8810630 | biostudies-literature

POISED (Peanut Oral Immunotherapy: Safety, Efficacy, and Discovery)

Project description:POISED (Peanut Oral Immunotherapy: Safety, Efficacy, and Discovery)

| PRJNA886099 | ENA

POISED (Peanut Oral Immunotherapy: Safety, Efficacy, and Discovery)

Project description:POISED (Peanut Oral Immunotherapy: Safety, Efficacy, and Discovery)

| PRJNA886098 | ENA

Selinexor, a First-in-Class XPO1 Inhibitor, Is Efficacious and Tolerable in Patients with Myelodysplastic Syndromes Refractory to Hypomethylating Agents

Project description:PURPOSE The median overall survival (OS) of patients with high-risk myelodysplastic syndromes (MDS) refractory to hypomethylating agents is less than 6 months and there is no standard therapy for such patients. Preclinical studies have shown that inhibition of the nuclear export protein XPO1 causes nuclear accumulation of p53 and disruption of NF-κB signaling, both relevant targets for MDS. We therefore sought to determine the safety, efficacy, and potential molecular correlates of response to selinexor, an oral selective inhibitor of XPO1, in MDS. PATIENTS AND METHODS We report the results of a phase 2 clinical trial of selinexor in high-risk MDS patients refractory to hypomethylating agents. The primary endpoint was overall response rate (ORR) and secondary endpoints included safety, response duration, and OS. RESULTS In 19 evaluable patients, ORR was 32% (95% CI, 13-57) with an additional 42% (95% CI, 24-71) achieving stable disease (SD). Median OS was 9.6 months (95% CI, 8.5-17.1) with median follow-up of 2.1 years. Grade 3 or 4 adverse events (AEs) in the first 3 patients (thrombocytopenia [n=3] and hyponatremia [n=1]) led to dose reduction to 60mg flat dose twice-weekly for two weeks followed by one week off, resulting in significantly improved tolerability. The most frequent adverse event (AE) thereafter was grade 1 or 2 nausea, anorexia and fatigue. These and other AEs were manageable with supportive care implementation. The presence of an SF3B1 mutation was significantly associated with response to selinexor (p=0.02) and correlative studies suggest splicing alterations were induced by selinexor and affected inflammatory pathways such as NF-κB. CONCLUSIONS Selinexor is safe and tolerable in MDS when given at 60mg twice weekly for two weeks with one week off. Responses were enriched in SF3B1 mutated patients.

2020-11-26 | GSE141147 | GEO

Efficacy and safety of ustekinumab treatment in patients with ulcerative colitis

Project description:UNIFI was a randomized placebo-controlled phase 3 clinical trial evaluating the efficacy and safety of ustekinumab (ClinicalTrials.gov Identifier: NCT02407236). Gene expression profiling by microarrays was carried out at baseline on biopsies from the sigmoid colon (15-20cm from anal verge) of patients (n=550) with moderate-to-severe ulcerative colitis and of healthy subjects (n=18). Ulcerative colitis patients received placebo (n=186) or ustekinumab (n=364). The effects of two different dosages were investigated: 130mg (n=180) and 6mg/kg (n=184).

2022-08-08 | GSE206285 | GEO

Enhanced safety and efficacy of protease-regulated CAR-T cell receptors

Project description:Enhanced safety and efficacy of protease-regulated CAR-T cell receptors

| PRJNA794116 | ENA

Safety and Efficacy of Intravenous Norepinephrine for Orthostatic Hypotension - ARD 6104

Project description:Safety and Efficacy of Intravenous Norepinephrine for Orthostatic Hypotension - ARD 6104

| PRJNA514385 | ENA

Safety and Efficacy of Intravenous Norepinephrine for Orthostatic Hypotension - ARD 6104

Project description:Safety and Efficacy of Intravenous Norepinephrine for Orthostatic Hypotension - ARD 6104

| PRJNA514386 | ENA

Efficacy and safety of ustekinumab treatment in patients with ulcerative colitis

Project description:Efficacy and safety of ustekinumab treatment in patients with ulcerative colitis