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

NCT03184558 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: BGBC007MK-3475 PN5302016-003608-30
• Study Type: interventional
• Target: 29
• Locations: 4 countries
• Sites: 17

Brief Summary

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.

Conditions

Triple Negative Breast Cancer; Inflammatory Breast Cancer Stage IV

Keywords

bemcentinib; TNBC; pembrolizumab; Keytruda; BGB324

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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.

  Until disease progression or death or withdrawal of consent whichever comes first, up to end of study (Up to 1 year)

Secondary Outcomes (4)

• Duration of Response (DOR)

  Until disease progression or death or withdrawal of consent whichever comes first, up to end of study (Up to 1 year)

• Disease Control Rate (DCR)

  Until disease progression or death or withdrawal of consent whichever comes first, up to end of study (Up to 1 year)

• Progression-free Survival (PFS)

  Until disease progression or death or withdrawal of consent whichever comes first, up to end of study (Up to 1 year)

• Overall Survival (OS)

  Until disease progression or death or withdrawal of consent whichever comes first, up to end of study (Up to 1 year)

Study Arms (1)

Bemcentinib (BGB324) + pembrolizumab

EXPERIMENTAL

Participants received Bemcentinib (BGB324) capsules orally once daily as a loading dose of 400 milligram (mg) on Days 1, 2, and 3. A dose of 200 mg pembrolizumab was given by intravenous infusion over 30 minutes every 3 weeks in all participants. Dosing of both drugs commenced on Day 1. On days when both BGB324 and pembrolizumab were given, pembrolizumab was given first and participants were observed for 1 hour after the end of infusion before BGB324 was administered. From Day 4 onward, participants received a daily maintenance dose of 200 mg along with Pembrolizumab 200 mg intravenous (IV) infusion over 30 minutes every 3 weeks until disease progression, until an unacceptable toxicity occurred that required treatment withdrawal or withdrawal of consent or until 106 weeks had passed.

Drug: Bemcentinib; pembrolizumab

Interventions

Bemcentinib; pembrolizumab DRUG

Bemcentinib is a selective Axl kinase inhibitor; pembrolizumab is a programmed death receptor-1 (PD-1) inhibitor.

Also known as: BGB324; Keytruda

Bemcentinib (BGB324) + pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed informed consent.
• Male and non-pregnant females who are aged 18 years or older at the time of provision of informed consent.
• Histopathologically or cytologically documented TNBC or TN-IBC. Tumors must have been confirmed negative for ER and partial response (PR) by immunohistochemistry (IHC) (\<1% positive tumor nuclei, as per ASCO-CAP guideline recommendations) and negative for human epidermal growth factor receptor 2 (HER2) by IHC or fluorescent or chromogenic in situ hybridization (FISH or CISH). Patients with equivocal HER2 results by IHC should have their negativity status confirmed by FISH.
• Locally advanced and unresectable or metastatic TNBC or triple negative inflammatory breast cancer.
• Received one or more prior therapies for TNBC or inflammatory breast cancer in the metastatic setting, and prior treatment (metastatic or (neo) adjuvant) must have included a prior taxane and/or anthracycline-based therapy.
• Has measurable disease as defined by RECIST 1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) and as determined by the site study team. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Provision of suitable tumor tissue for the analysis of Axl kinase expression and PD-L1 expression.
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
• Life expectancy of at least 3 months.
• Adequate organ function confirmed at Screening and within 10 days of initiating treatment, as evidenced by:
• Platelet count ≥100,000 /mm3;
• Hemoglobin ≥9.0 g/dL (≥5.6 mmol/L);.
• Absolute neutrophil count (ANC) \>1,500 /mm\^3;
• Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal (ULN), or ≤5 times the ULN for patients with liver metastases;
• Total bilirubin ≤1.5 times the ULN, or direct bilirubin \<ULN for patients with total bilirubin levels \>1.5xULN;

You may not qualify if:

• Has disease that is suitable for local therapy administered with curative intent.
• More than 3 previous lines of therapy in the metastatic setting.
• Has received prior therapy with an immunomodulatory agent.
• Has a known additional malignancy that is progressing or requires active treatment. Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• History of the following cardiac conditions:
• Congestive cardiac failure of \>Grade II severity according to the New York Heart Association (NYHA);
• Ischemic cardiac event including myocardial infarction within 3 months prior to first dose;
• Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension (i.e. sustained systolic BP \>160 mmHg or diastolic BP \>90 mmHg), or need to change medication due to lack of disease control within 6 weeks prior to the provision of consent;
• History or presence of sustained bradycardia (≤55 BPM), left bundle branch block, cardiac pacemaker or ventricular arrhythmia. Note: Patients with a supraventricular arrhythmia requiring medical treatment, but with a normal ventricular rate are eligible;
• Family history of long QTc syndrome; personal history of long QTc syndrome or previous drug-induced QTc prolongation of at least Grade 3 (QTc \>500 ms).
• Abnormal left ventricular ejection fraction on echocardiography or Multi Gated Acquisition Scan (MUGA) (less than the lower limit of normal for a patient of that age at the treating institution or \<45%, whichever is lower).
• Current treatment with any agent known to cause Torsades de Pointes which cannot be discontinued at least five half-lives or two weeks prior to the first dose of study treatment.
• Screening 12-lead ECG with a measurable QTc interval according to Fridericia's correction \>450 ms.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.

Sponsors & Collaborators

• BerGenBio ASA: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (17)

City of Hope Cancer Center

Duarte, California, 91010-3012, United States

Location

Sharp memorial Hospital, 7901 Frost Street,

San Diego, California, 92123-2701, United States

Location

Saint Luke's Cancer Institute

Kansas City, Missouri, 64111, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Magee-Womens Hospital, UPMC Cancer Pavilion

Pittsburgh, Pennsylvania, 15232-1309, United States

Location

Haukeland University Hospital

Bergen, 5021, Norway

Location

University General Hospital of Alicante

Alicante, 03010, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Germans Trias i Pujol - Institut Catala d'Oncologia

Barcelona, 08916, Spain

Location

Hospital Universitario Amau de Vilanova de Lieda, Servicio de Oncologia

Lleida, 25198, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Imperial College Healthcare NHS Trust, Charing Cross Hospital

London, W6 8RF, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospitals, City Campus, Hucknall Road

Nottingham, NG5 1 PB, United Kingdom

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Inflammatory Breast Neoplasms

Interventions

bemcentinib; pembrolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

None of the participants achieved CR or PR. As there were no responses, the study was terminated. It was planned to terminate the trial in favor of the null hypothesis of futility when 5 or fewer responses were observed in 28 participants.

Results Point of Contact

• Title: BerGenBio Clinical Team
• Organization: BerGenBio ASA

trialsites@bergenbio.com

+47 559 61 159

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Extension to Simon's 2-stage design allowing termination at the end of Stage 1 for either futility or efficacy.

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 12, 2017
• Study Start: July 26, 2017
• Primary Completion: August 20, 2018
• Study Completion: August 20, 2018
• Last Updated: November 9, 2021
• Results First Posted: November 9, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Proposal should be directed to HYPERLINK "mailto:clinical@bergenbio.com" clinical@bergenbio.com. To gain access, data requestors will need to sign a data access agreement.

Locations

NO (1); ES (7); GB (4); US (5)