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NCT03184558

Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With TNBC

Terminated Phase 2 Results posted Last updated 9 November 2021
What this trial tests

Phase 2 trial testing Bemcentinib; pembrolizumab in Triple Negative Breast Cancer in 29 participants. Terminated before completion.

Timeline
26 July 2017
Primary endpoint
20 August 2018
20 August 2018

Quick facts

Lead sponsorBerGenBio ASA
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment29
Start date26 July 2017
Primary completion20 August 2018
Estimated completion20 August 2018
Sites17 locations across United Kingdom, United States, Spain, Norway

Drugs / interventions tested

Conditions studied

Sponsor

BerGenBio ASA — full company profile →

Who can join

18 and older, any sex, with Triple Negative Breast Cancer or Inflammatory Breast Cancer Stage IV. 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.

Objective Response Rate (ORR) Primary · Until disease progression or death or withdrawal of consent whichever comes first, up to end of study (Up to 1 year)

ORR is defined as the percentage of evaluable participants who had at least one confirmed overall response of complete response (CR) or partial response (PR) according to the modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. CR: Disappearance of all target lesions (TLs) since baseline, any pathological lymph nodes selected as TLs must have a reduction in short axis to less than (\<) 10 millimeter (mm). PR: At least a 30 percent decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters.

GroupValue95% CI
Bemcentinib + Pembrolizumab0
Disease Control Rate (DCR) Secondary · Until disease progression or death or withdrawal of consent whichever comes first, up to end of study (Up to 1 year)

DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD). CR: Disappearance of all target lesions (TLs) since baseline, any pathological lymph nodes selected as TLs must have a reduction in short axis to \< 10 mm. PR: At least a 30 percent decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters. SD per modified RECIST 1.1 defined as: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

GroupValue95% CI
Bemcentinib + Pembrolizumab3.4
Progression-free Survival (PFS) Secondary · Until disease progression or death or withdrawal of consent whichever comes first, up to end of study (Up to 1 year)

PFS was defined as the duration from start of treatment until the date of radiological disease progression (the date on which the confirmed progression was initially observed) or the date of death (regardless of cause of death), whichever was earlier.

GroupValue95% CI
Bemcentinib + Pembrolizumab13.112.4 – 18.3
Overall Survival (OS) Secondary · Until disease progression or death or withdrawal of consent whichever comes first, up to end of study (Up to 1 year)

OS was defined as the time from the first dose of study treatment until the date of death (from any cause and irrespective of any subsequent anti-cancer treatment given).

GroupValue95% CI
Bemcentinib + Pembrolizumab32.013.6 – 37.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 1 year. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Bemcentinib + Pembrolizumab
Serious: 22/29 (76%)
Deaths: 16/29

Serious adverse events (35 terms)

ReactionSystemBemcentinib + Pembrolizumab
PyrexiaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Rash maculo-papularSkin and subcutaneous tissue disorders
Febrile neutropeniaBlood and lymphatic system disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Transaminases increasedInvestigations
Rash generalisedSkin and subcutaneous tissue disorders
Adverse drug reactionGeneral disorders
Face oedemaGeneral disorders
Oedema peripheralGeneral disorders
Pruritus generalisedSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
Urinary tract infectionInfections and infestations
Neutropenic sepsisInfections and infestations
PneumoniaInfections and infestations
Septic shockInfections and infestations
Upper respiratory tract infectionInfections and infestations
ThrombocytopeniaBlood and lymphatic system disorders
Hypovolaemic shockVascular disorders
Jugular vein thrombosisVascular disorders
LymphoedemaVascular disorders
Autoimmune hepatitisHepatobiliary disorders
Hepatitis acuteHepatobiliary disorders
Other adverse events (121 terms — click to expand)

ReactionSystemBemcentinib + Pembrolizumab
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
NauseaGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
AnaemiaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
PyrexiaGeneral disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
Blood alkaline phosphatase increasedInvestigations
Musculoskeletal painMusculoskeletal and connective tissue disorders
Oral candidiasisInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Abdominal distensionGastrointestinal disorders
Electrocardiogram QT prolongedInvestigations
HypokalaemiaMetabolism and nutrition disorders
PainGeneral disorders
Influenza like illnessGeneral disorders
DyspepsiaGastrointestinal disorders
White blood cell count decreasedInvestigations
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
Neck painMusculoskeletal and connective tissue disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Rash generalisedSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
TremorNervous system disorders
Hot flushVascular disorders
Oedema peripheralGeneral disorders
Axillary painGeneral disorders
ChillsGeneral disorders
Lymphocyte count decreasedInvestigations
Blood creatinine increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Pyrexia, Dyspnoea, Alanine aminotransferase increased, Aspartate aminotransferase increased, Rash maculo-papular, Febrile neutropenia, Pleural effusion, Transaminases increased.

Data from ClinicalTrials.gov NCT03184558 adverse events section.

Sponsor's own description

This is an open label, single arm, multi-centre phase II study to assess the anti-tumour activity and safety of bemcentinib (BGB324) in combination with pembrolizumab in participants with previously treated, locally advanced and unresectable, or metastatic TNBC or TN-IBC. The primary objective is objective response rate.

Publications & conference data

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

  1. Recent advances in therapeutic strategies for triple-negative breast cancer.
    Li Y, Zhang H, Merkher Y, Chen L, et al · · 2022 · cited 643× · PMID 36038913 · DOI 10.1186/s13045-022-01341-0
  2. AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications.
    Zhu C, Wei Y, Wei X. · · 2019 · cited 398× · PMID 31684958 · DOI 10.1186/s12943-019-1090-3
  3. Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets.
    Di X, Gao X, Peng L, Ai J, et al · · 2023 · cited 358× · PMID 37518181 · DOI 10.1038/s41392-023-01501-9
  4. Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment.
    Myers KV, Amend SR, Pienta KJ. · · 2019 · cited 333× · PMID 31088471 · DOI 10.1186/s12943-019-1022-2
  5. The clinical promise of immunotherapy in triple-negative breast cancer.
    Vikas P, Borcherding N, Zhang W. · · 2018 · cited 111× · PMID 30573992 · DOI 10.2147/cmar.s185176
  6. Leveraging NKG2D Ligands in Immuno-Oncology.
    Fuertes MB, Domaica CI, Zwirner NW. · · 2021 · cited 110× · PMID 34394116 · DOI 10.3389/fimmu.2021.713158
  7. Gas6/Axl Signaling Pathway in the Tumor Immune Microenvironment.
    Tanaka M, Siemann DW. · · 2020 · cited 109× · PMID 32660000 · DOI 10.3390/cancers12071850
  8. Phosphatidylserine receptors enhance SARS-CoV-2 infection.
    Bohan D, Van Ert H, Ruggio N, Rogers KJ, et al · · 2021 · cited 99× · PMID 34797899 · DOI 10.1371/journal.ppat.1009743

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Other recruiting trials for Triple Negative Breast Cancer

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