A Phase II Multi Center Study of BGB324 in Combination With Pembrolizumab in Patients With Previously Treated Advanced Adenocarcinoma of the Lung
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- BerGenBio ASA
- Enrollment
- 99
- Locations
- 13
- Primary Endpoint
- Objective Response Rate (ORR)
Overview
Brief Summary
This is an open-label, multi-center, single arm, phase II study to assess the anti-tumor activity and safety of bemcentinib in combination with pembrolizumab in up to 106 participants with previously treated, advanced adenocarcinoma of the lung. The study will enrol three cohorts of participants with previously treated, advanced adenocarcinoma of the lung. Cohort A will consist of participants who received a maximum of 1 prior line of platinum-containing chemotherapy and no prior immunotherapy. Cohort B will consist of participants who received a maximum of one prior line of an anti-programmed death receptor (PD)-(L)1 therapy (monotherapy). Cohort C will consist of participants who received a maximum of one prior line of therapy with an anti-PD-(L)1 therapy in combination with a platinum-containing chemotherapy. The primary objective is to assess the anti-tumor activity of bemcentinib in combination with pembrolizumab.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- 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 were aged 18 years or older at the time of provision of informed consent.
- •Histopathologically or cytologically documented Stage IV adenocarcinoma NSCLC; Note: Patients with a mixed cell histology including a significant area of adenocarcinoma histology were eligible.
- •Cohort A: Had disease progression on or after a prior platinum-containing chemotherapy; Note: Patients with EGFR mutations or ALK genomic rearrangements had to have documented disease progression on at least 1 licensed therapy for these indications and may not have received platinum-containing chemotherapy.
- •Had received a maximum of 1 prior line of an anti-PD-(L)1 therapy (monotherapy).
- •Must have had disease control containing at least 2 doses of anti-PD-(L)1 therapy. Disease control was defined as:
- •i. Stable disease for at least 12 weeks (date of first progression on anti-PD-(L)1 therapy) Or ii. Confirmed PR or CR - confirmatory scan must have been performed \>4 weeks from initial scan) c) Had disease progression when entering Screening (first date of progression of disease was taken as end date of response to previous anti-PD-(L)1 therapy) and this must have been within 12 weeks of last dose of treatment containing an anti-PD-(L)1 therapy. Progression should have been confirmed in 1 of the following ways: i. Having had 2 scan assessments completed at least 4 weeks apart, both showing progression according to response evaluation criteria in solid tumors (RECIST) 1.113 or ii. Having had 1 scan assessment completed showing disease progression according to standards used for previous therapy combined with rapid disease progression / clinical progression.
- •Had received a maximum of 1 prior line of an anti-PD-(L)1 therapy in combination with a platinum-containing chemotherapy.
- •Must have had disease control containing at least 2 doses of anti-PD-(L)1 therapy. Disease control was defined as:
- •i. Stable disease for at least 12 weeks (date of first progression on anti-PD-(L)1 therapy) Or ii. Confirmed PR or CR - confirmatory scan must be performed \>4 weeks from initial scan c) Had disease progression when entering Screening (first date of progression of disease was taken as end date of response to previous anti-PD-(L)1 therapy) and this must have been within 12 weeks of last dose of treatment containing an anti-PD-(L)1 therapy. Progression had to be confirmed in 1 of the following ways: i. Having had 2 scan assessments completed at least 4 weeks apart, both showing progression according to RECIST 1.113 or ii. Having had 1 scan assessment completed showing disease progression according to standards used for previous therapy combined with rapid disease progression/clinical progression
Exclusion Criteria
- •Had disease suitable for local therapy administered with curative intent.
- •Had received more than 1 prior line of chemotherapy for advanced or metastatic adenocarcinoma of the lung. For all cohorts: Note: Patients may have received additional prior radiotherapy or chemotherapy in the adjuvant setting, providing it was completed at least 6 months prior to start of study treatment.
- •Cohort A: Had received prior therapy with an immunomodulatory agent; Cohort B: Had received prior chemotherapy alone or in combination with immunotherapy in the metastatic setting.
- •Had a known additional malignancy that was progressing or required active treatment; Note: Exceptions included basal cell carcinoma of the skin, squamous cell carcinoma of the skin that had undergone potentially curative therapy, or in situ cervical cancer.
- •Had known active central nervous system (CNS) metastases and/or carcinomatous meningitis; Note: Patients with previously treated brain metastases could participate provided they were stable (without evidence of progression by scans \[using the identical modality for each assessment, either MRI or CT scan\] for at least 4 weeks prior to the first dose of study treatment and any neurological symptoms had returned to Baseline), having no evidence of new or enlarging brain metastases, and were not using steroids for at least 7 days prior to study treatment.
- •History of the following cardiac conditions:
- •Congestive cardiac failure of \> Grade II severity according to the New York Heart Association (defined as symptomatic at less than ordinary levels of activity).
- •Ischemic cardiac event including, myocardial infarction, within 3 months before the first dose.
- •Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension (ie, sustained systolic blood pressure (BP) \>160 mm Hg or diastolic BP \>90 mm Hg), or need to change medication because of lack of disease control within 6 weeks before the provision of consent.
- •History or presence of sustained bradycardia (≤55 beats per minute), left bundle branch block, cardiac pacemaker, or ventricular arrhythmia; Note: Patients with a supraventricular arrhythmia requiring medical treatment but with a normal ventricular rate were eligible.
Arms & Interventions
Cohort A Bemcentinib + pembrolizumab
Cohort A bemcentinib (BGB324) in combination with pembrolizumab will be administered to participants with previously treated, advanced adenocarcinoma of the lung who received a maximum of 1 prior line of platinum-containing chemotherapy and no prior immunotherapy.
Intervention: Pembrolizumab (Drug)
Cohort A Bemcentinib + pembrolizumab
Cohort A bemcentinib (BGB324) in combination with pembrolizumab will be administered to participants with previously treated, advanced adenocarcinoma of the lung who received a maximum of 1 prior line of platinum-containing chemotherapy and no prior immunotherapy.
Intervention: Bemcentinib (Drug)
Cohort B Bemcentinib + pembrolizumab
Cohort B bemcentinib (BGB324) in combination with pembrolizumab will be administered to participants with previously treated, advanced adenocarcinoma of the lung who received a maximum of one prior line of an anti-PD-(L)1 therapy (monotherapy).
Intervention: Pembrolizumab (Drug)
Cohort B Bemcentinib + pembrolizumab
Cohort B bemcentinib (BGB324) in combination with pembrolizumab will be administered to participants with previously treated, advanced adenocarcinoma of the lung who received a maximum of one prior line of an anti-PD-(L)1 therapy (monotherapy).
Intervention: Bemcentinib (Drug)
Cohort C Bemcentinib + pembrolizumab
Cohort C bemcentinib (BGB324) in combination with pembrolizumab will be administered to participants with previously treated, advanced adenocarcinoma of the lung who received a maximum of one prior line of therapy with an anti-PD-(L)1 therapy in combination with a platinum-containing chemotherapy.
Intervention: Pembrolizumab (Drug)
Cohort C Bemcentinib + pembrolizumab
Cohort C bemcentinib (BGB324) in combination with pembrolizumab will be administered to participants with previously treated, advanced adenocarcinoma of the lung who received a maximum of one prior line of therapy with an anti-PD-(L)1 therapy in combination with a platinum-containing chemotherapy.
Intervention: Bemcentinib (Drug)
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: The disease response is the best improvement or change in a participants cancer burden, as measured from baseline (screening) and then measured again at regular intervals over the whole period of the study, an average of 24 months.
Objective Response Rate (ORR) includes all participants who have a partial (PR) or complete response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for target lesions and assessed by CT scan or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions,. ORR was defined as the percentage of evaluable patients who had at least 1 confirmed overall response CR or PR according to modified RECIST 1.1 evaluation and definitions of disease response.
Secondary Outcomes
- Disease Control Rate(Disease response is assessed every 9 weeks for the first 45 weeks and then every 12 weeks until disease progression (worsens) or study completion, an average of 24 months.)
- Duration of Response(Disease response is assessed every 9 weeks for the first 45 weeks and then every 12 weeks until disease progression or study completion, an average of 24 months.)
- Overall Survival(Survival visits are conducted every 12 weeks after disease progression until death or until study completion (an average of 24 months).)
- Number of Participants With Adverse Events (AEs)(Adverse events are collected from the date of consent until up to 120 days after cessation of both treatments, up to 24 months of treatment, followed by an additional 120 days following cessation, up to 27 months total.)
- Pharmacokinetic (PK) Parameters: Maximum Observed Concentration (Cmax)(Up to 106 weeks)
- PK Parameters: Area Under the Curve (AUC)(Cycle 1 Day 1 and Day 3 pre-dose, and 2, 4, 6, 8 hours post-dose; Cycle 1 Day 2 , Day 4 ,Day 8 and Day 15 pre-dose; Cycle 2 Day 1, and Cycle 3 Day 1., pre-dose. Each cycle is 21 days in duration.)
- PK Parameters: Elimination Half-life (T½)(Up to 106 weeks)
- Frequency of Clinical Laboratory, Vital Signs, and Electrocardiogram (ECG) Abnormalities.(Up to 106 weeks)
- Progression-free Survival (PFS)(Disease assessments are conducted at screening and then every 9 weeks for the first 45 weeks and then every 12 weeks until disease progression or death, whichever comes first, up to study completion (an average of 24 months))