A PHP Error was encountered

Severity: Warning

Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests

Filename: helpers/my_audit_helper.php

Line Number: 143

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: Attempt to read property "Count" on bool

Filename: helpers/my_audit_helper.php

Line Number: 3100

Backtrace:

File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler

File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global

File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword

File: /var/www/html/index.php
Line: 316
Function: require_once

Phase IIa Study of PLX2853 in Gynecologic Cancers With Known ARID1A Mutation and Phase Ib/IIa Study of PLX2853/Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer. | LitMetric

AI Article Synopsis

  • BET domain proteins play a role in cancer development and PLX2853 is a small-molecule inhibitor that may help overcome platinum resistance in ovarian cancer.
  • A clinical study was conducted to test PLX2853 both alone and in combination with carboplatin in patients with advanced gynecologic cancers, focusing on safety, tolerability, and efficacy.
  • Although the study didn't meet specific response criteria, it showed some clinical activity, suggesting further investigation of BET inhibitors in combination with other treatments may be beneficial for patients with certain mutations.

Article Abstract

Purpose: The Bromodomain and Extra-Terminal (BET) domain proteins facilitate the development of many human cancers via epigenetic regulation. BET inhibitors may be effective in reversing platinum resistance in ovarian cancer (OC) and may generate synthetic lethality with loss. PLX2853 is an orally active, small-molecule inhibitor of BET bromodomain-mediated interactions that exhibits low nanomolar potency in blocking all four BET family members.

Methods: We conducted a multicenter and open-label study with two parallel arms: a phase IIa study of PLX2853 monotherapy in patients with advanced gynecologic malignancies with an mutation and a phase Ib/IIa combination study of PLX2853 plus carboplatin in women with platinum-resistant OC. The primary objectives were safety and tolerability for phase Ib and efficacy for both phase IIa portions. Thirty-four of 37 enrolled patients completed at least one post-baseline response assessment.

Results: Of the 14 evaluable patients on the monotherapy arm, 1 (7.1%) achieved a best overall response of partial response (PR), 5 (35.7%) had stable disease (SD), and 8 (57.1%) had progressive disease (PD). Of the 20 evaluable patients on the combination arm, 1 (5.0%) had PR, 9 (45.0%) had SD, and 10 (50%) had PD.

Conclusion: This study confirmed the safety profile of PLX2853 and demonstrated the feasibility of combination with carboplatin. Although these results did not meet the prespecified response criteria, evidence of clinical activity highlights the rationale for further exploration of BET inhibitors in patients with -mutated gynecologic malignancies, possibly in combination with agents targeting potential feedback mechanisms such as the PI3K pathway.

Download full-text PDF

Source
http://dx.doi.org/10.1200/PO.23.00235DOI Listing

Publication Analysis

Top Keywords

phase iia
12
study plx2853
12
iia study
8
mutation phase
8
phase ib/iia
8
ovarian cancer
8
bet inhibitors
8
gynecologic malignancies
8
evaluable patients
8
phase
6

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: