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NCT04493619

PLX2853 as a Single Agent in Advanced Gynecological Malignancies and in Combination With Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer

Terminated Phase 1, PHASE2 Results posted Last updated 4 November 2024
What this trial tests

Phase 1, PHASE2 trial testing PLX2853 in Gynecologic Neoplasms in 37 participants. Terminated before completion.

Timeline
11 August 2020
Primary endpoint
25 April 2022
25 April 2022

Quick facts

Lead sponsorOpna Bio LLC
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment37
Start date11 August 2020
Primary completion25 April 2022
Estimated completion25 April 2022
Sites9 locations across Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Opna Bio LLC — full company profile →

Who can join

18 and older, female only, with Gynecologic Neoplasms or Epithelial Ovarian Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 1b (PLX2853 + Carboplatin Combination): Establish the Number of Participants Reaching MTD/RP2D for the Combination of PLX2853 and Carboplatin Primary · From time of first dose of PLX2853 and carboplatin until 30 days of end of treatment an average of 6 months.

MTD is defined as the maximum tolerated dose, which is determined from dose-limiting toxicity. If DLTs are observed in 2 or more of 6 subjects (or ≥33% of the cohort) at a dose level, the dose at which this occurs will be considered intolerable and the MTD will have been exceeded. The MTD is the dose below the intolerable dose. RP2D is the recommended Phase 2 dose, which was determined to be 80 mg

GroupValue95% CI
PLX2853 Phase 2a Monotherapy0
PLX2853 + Carboplatin Phase 1b/2a Combination Therapy0

Adverse events — posted to ClinicalTrials.gov

Time frame: Through 30 days after last dose of study drug, an average of 6 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PLX2853 Phase 2a Monotherapy
Serious: 6/14 (43%)
Deaths: 5/14
PLX2853 + Carboplatin Phase 1b/2a Combination Therapy
Serious: 10/23 (43%)
Deaths: 11/23

Serious adverse events (21 terms)

ReactionSystemPLX2853 Phase 2a MonotherapyPLX2853 + Carboplatin Phas…
anemiaBlood and lymphatic system disorders
dehydrationMetabolism and nutrition disorders
obstruction gastricGastrointestinal disorders
sepsisInfections and infestations
abdominal painGastrointestinal disorders
thrombocytopeniaBlood and lymphatic system disorders
hepatic hematomaHepatobiliary disorders
fatigueGeneral disorders
large intenstinal obstructionGastrointestinal disorders
small intestinal obstructionGastrointestinal disorders
abdominal infectionInfections and infestations
confusional statePsychiatric disorders
duodenal obstructionGastrointestinal disorders
gastric haemmorhageGastrointestinal disorders
hyponatremiaMetabolism and nutrition disorders
infusion related reactionInjury, poisoning and procedural complications
lethargyNervous system disorders
pneumoniaInfections and infestations
procedural pneumothoraxInjury, poisoning and procedural complications
pyrexiaGeneral disorders
syncopeNervous system disorders
Other adverse events (60 terms — click to expand)

ReactionSystemPLX2853 Phase 2a MonotherapyPLX2853 + Carboplatin Phas…
NauseaGastrointestinal disorders
Platelet count decreasedInvestigations
FatigueGeneral disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypomagnesemiaMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
HeadacheNervous system disorders
HyponatremiaMetabolism and nutrition disorders
Decreased white blood cellInvestigations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
HyperglycemiaMetabolism and nutrition disorders
Neutrophil count decreasedInvestigations
ThrombocytopeniaBlood and lymphatic system disorders
Weight lossInvestigations
Abdominal distensionGastrointestinal disorders
Bilirubin increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
DysgeusiaNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Gastroesophageal reflex diseaseGastrointestinal disorders
Infusion related reactionInjury, poisoning and procedural complications
ProteinuriaRenal and urinary disorders
PyrexiaGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
FlatulenceGastrointestinal disorders
HematuriaRenal and urinary disorders
Influenza like illnessGeneral disorders
Lymphocyte count decreasedInvestigations
EdemaGeneral disorders
Pelvic painReproductive system and breast disorders
HypertensionVascular disorders

Most-reported serious reactions: anemia, dehydration, obstruction gastric, sepsis, abdominal pain, thrombocytopenia, hepatic hematoma, fatigue.

Data from ClinicalTrials.gov NCT04493619 adverse events section.

Sponsor's own description

The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in Advanced Gynecological Malignancies with a Known ARID1A Mutation and PLX2853/Carboplatin Combination Therapy in Platinum-Resistant Epithelial Ovarian Cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Epigenetics-targeted drugs: current paradigms and future challenges.
    Dai W, Qiao X, Fang Y, Guo R, et al · · 2024 · cited 131× · PMID 39592582 · DOI 10.1038/s41392-024-02039-0
  2. Treating ARID1A mutated cancers by harnessing synthetic lethality and DNA damage response.
    Mandal J, Mandal P, Wang TL, Shih IM. · · 2022 · cited 68× · PMID 36123603 · DOI 10.1186/s12929-022-00856-5
  3. Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.
    Yin N, Li X, Zhang X, Xue S, et al · · 2024 · cited 48× · PMID 38773064 · DOI 10.1038/s41392-024-01826-z
  4. ARID1A in cancer: Friend or foe?
    Fontana B, Gallerani G, Salamon I, Pace I, et al · · 2023 · cited 36× · PMID 36890819 · DOI 10.3389/fonc.2023.1136248
  5. Synthetic Lethality in Ovarian Cancer.
    Chandrasekaran A, Elias KM. · · 2021 · cited 34× · PMID 34518297 · DOI 10.1158/1535-7163.mct-21-0500
  6. ARID1A Mutation in Metastatic Breast Cancer: A Potential Therapeutic Target.
    Cheng X, Zhao JX, Dong F, Cao XC. · · 2021 · cited 22× · PMID 34804958 · DOI 10.3389/fonc.2021.759577
  7. Bromodomain-containing protein 4 (BRD4): a key player in inflammatory bowel disease and potential to inspire epigenetic therapeutics.
    Ma Z, Bolinger AA, Zhou J, Tian B. · · 2023 · cited 21× · PMID 36710583 · DOI 10.1080/14728222.2023.2175317
  8. An updated patent review of BRD4 degraders.
    Ma Z, Zhang C, Bolinger AA, Zhou J. · · 2024 · cited 17× · PMID 39219068 · DOI 10.1080/13543776.2024.2400166

Verify or expand the search:

Other trials of PLX2853

Trials testing the same drug.

Other recruiting trials for Gynecologic Neoplasms

Currently open trials in the same condition.

Other Opna Bio LLC trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing