A Phase II, Multi Centre Study of BGB324 in Combination With Pembrolizumab in Patients With Previously Treated, Locally Advanced and Unresectable or Metastatic Triple Negative Breast Cancer (TNBC) or Triple Negative Inflammatory Breast Cancer (TN-IBC)
Overview
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- BerGenBio ASA
- Enrollment
- 29
- Locations
- 17
- Primary Endpoint
- Objective Response Rate (ORR)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •Life expectancy of at least 3 months.
- •Adequate organ function confirmed at Screening and within 10 days of initiating treatment, as evidenced by:
Exclusion Criteria
- •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;
Arms & Interventions
Bemcentinib (BGB324) + pembrolizumab
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.
Intervention: Bemcentinib; pembrolizumab (Drug)
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: 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.
Secondary Outcomes
- 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))
- 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))