Study Evaluating Safety, Tolerability and Clinical Activity of GSK2857916 in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Multiple Myeloma (RRMM)
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT03848845
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This is a phase I/II, single arm, open label, two-part study that will assess safety, tolerability and clinical activity of GSK2857916 given in combination with a programmed cell death-1 (PD-1) inhibitor pembrolizumab in subjects with RRMM. This study will enroll adult subjects with RRMM, who have undergone stem cell transplant or who are considered transplant ineligible. Part 1 is a dose escalation phase to evaluate the safety and tolerability of escalating doses of GSK2857916 in combination with 200 milligrams (mg) pembrolizumab to establish the recommended phase 2 dose (RP2D). The following dose levels of GSK2857916 are planned to be studied: 2.5 milligrams per kilograms (mg/kg) (dose level \[DL\] 1) and 3.4 mg/kg (DL2). Part 2 is a dose expansion cohort. Once the RP2D has been identified, an expansion cohort will open for enrolment to confirm the safety profile and to evaluate the clinical activity of the combination. Up to 40 evaluable subjects will be enrolled in this two-part study (up to 12 in Part 1, and 28 in Part 2).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 41
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2: Expansion cohort Pembrolizumab Subjects will receive belantamab mafodotin at RP2D along with 200 mg pembrolizumab via IV infusion on Day 1 of each 21-day cycle. There will be maximum of 35 cycles of combination treatment. Part 1: Dose escalation Pembrolizumab Subjects will receive belantamab mafodotin at escalating doses of 2.5 milligrams per kilograms (mg/kg) and 3.4 mg/kg along with 200 mg pembrolizumab via intravenous (IV) infusion on Day 1 of each 21-day cycle to establish RP2D. There will be maximum of 35 cycles of combination treatment. Part 1: Dose escalation belantamab mafodotin Subjects will receive belantamab mafodotin at escalating doses of 2.5 milligrams per kilograms (mg/kg) and 3.4 mg/kg along with 200 mg pembrolizumab via intravenous (IV) infusion on Day 1 of each 21-day cycle to establish RP2D. There will be maximum of 35 cycles of combination treatment. Part 2: Expansion cohort belantamab mafodotin Subjects will receive belantamab mafodotin at RP2D along with 200 mg pembrolizumab via IV infusion on Day 1 of each 21-day cycle. There will be maximum of 35 cycles of combination treatment.
- Primary Outcome Measures
Name Time Method Part 1 - Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Up to approximately 31 months An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function.
Part 1 - Number of Participants With Dose Limiting Toxicities (DLTs) Up to 21 days DLT is an AE that is considered by the investigator to be clinically relevant and attributed to the study therapy during the 21 day DLT period and meets at least one of the DLT criteria: any Grade 4 and 3 non-hematologic toxicity, any Grade 3 or greater non-hematologic laboratory value, hematologic toxicity lasting \>=7 days, except Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia associated with clinically significant bleeding. Grade 3 or greater febrile neutropenia lasting \>48 hours (h) despite adequate treatment, Nephrotoxicity requiring dialysis, Liver toxicity, prolonged delay (\>14 days) in initiating Cycle 2 due to any treatment (pembrolizumab or GSK2857916) related toxicity, any treatment-related toxicity that causes discontinuation of treatment during Cycle 1, any other toxicity considered to be dose-limiting that occurs beyond 21 days and any other event which in the judgment of the investigator and GlaxoSmithKline Medical Monitor is considered to be a DLT.
Part 1 - Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters Baseline (Day 1) and up to approximately 31 months Blood samples were collected for the analysis of following hematology parameters: hemoglobin, White blood cells (WBC) count, lymphocytes, neutrophils and platelet count. The laboratory parameters were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Any worst-case post baseline increase in grade along with any increase to a maximum grade of 3 and a maximum grade of 4 are presented.
Part 1 - Number of Participants With Worst-case Change Post-baseline in Hematology Parameters Baseline (Day 1) and up to approximately 31 months Blood samples were collected for the analysis of following hematology parameters: basophils, eosinophils, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), erythrocytes, hematocrit, monocytes, neutrophils and reticulocyte. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented.
Part 1 - Number of Participants With Worst-case Grade Change From Baseline in Lab Chemistry Parameters Baseline (Day 1) and up to approximately 31 months Blood samples were collected for the analysis of clinical chemistry parameters: glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), blood bilirubin, calcium, creatine kinase (CPK), creatinine, gamma glutamyl transferase (GGT), magnesium, phosphate, potassium and sodium. Laboratory parameters were graded according to NCI-CTCAE version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Any worst case post baseline increase in grade along with any increase to a maximum grade of 3 and a maximum grade of 4 are presented.
Part 1 - Number of Participants With Worst-case Change Post-baseline in Lab Chemistry Parameters Baseline (Day 1) and up to 31 months Blood samples were collected for the analysis of following chemistry parameters: calcium, carbon dioxide, chloride, direct bilirubin, protein, thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3). The summaries of worst case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented.
Part 1 - Number of Participants With Worst-case Change Post-baseline Urinalysis Results Baseline (Day 1) and up to approximately 31 months Urine samples were collected to assess urine glucose, protein, occult blood and ketones using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for urinalysis parameters were recorded as no change/decreased and any increase. Data for worst-case post baseline urinalysis results is presented.
Part 1 - Changes From Baseline in Urine Potential of Hydrogen (pH) Baseline (Day 1) and Week 46 Urine samples were collected from participants to assess urine pH levels. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Part 1 - Changes From Baseline in Urine Specific Gravity Baseline (Day 1) and Week 46 Urine samples were collected from participants to assess urine specific gravity. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Part 1 - Number of Participants With Worst-case Grade Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Baseline (Day 1) and up to approximately 31 months DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.03. For SBP: Grade 0 (\<=120 millimeter of mercury \[mmHg\]), Grade 1 (121-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). For DBP: Grade 0 (\<=80 mmHg), Grade 1 (81-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). Higher grade indicates greater severity. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst-case post baseline with any grade increase and a maximum post-baseline grade increase to Grade 3 from their baseline grade are presented.
Part 1 - Number of Participants With Worst-case Change From Baseline in Vital Signs: Pulse Rate and Body Temperature Baseline (Day 1) and up to approximately 31 months Vital signs (pulse rate and temperature) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. The abnormal vital sign ranges were: For pulse rate (low \<60 beats per minute \[bpm\] and high \>100 bpm); For body temperature (\<=35 degrees Celsius or \>=38 degrees Celsius). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Data for worst case change from baseline was presented as Baseline to low, Baseline to Normal or No change and Baseline to High.
Part 2 - Percentage of Participants With Overall Response Rate (ORR) Up to approximately 31 months ORR was defined as the percentage of participants with a confirmed partial response (PR) or better (i.e., PR, very good partial response \[VGPR\], complete response \[CR\] and stringent complete response \[sCR\]), according to the International Myeloma Working Group (IMWG) Response Criteria. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component \<100 mg/24 h; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 h.
- Secondary Outcome Measures
Name Time Method Part 1 - Percentage of Participants With Overall Response Rate (ORR) Up to approximately 178 weeks ORR was defined as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR), according to the IMWG Response Criteria. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR \>= 90% reduction in serum M-component plus urine M-component \<100 mg/24 h; PR = \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 mg/24 h.
Part 2 - Number of Participants With Worst-case Change Post-baseline in Hematology Parameters Baseline (Day 1) and up to approximately 178 weeks Blood samples were collected for the analysis of following hematology parameters: basophils, eosinophils, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), Erythrocytes, hematocrit, monocytes, neutrophils and reticulocyte. The summaries of worst-case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. The number of participants with decreases to low from baseline, changes to normal or no changes from baseline, and increases to high values have been presented.
Part 2 - Number of Participants With Worst-case Grade Change From Baseline in Lab Chemistry Parameters Baseline (Day 1) and up to approximately 178 weeks Blood samples were collected for the analysis of clinical chemistry parameters: glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), blood bilirubin, calcium, creatine kinase (CPK), creatinine, gamma glutamyl transferase (GGT), magnesium, phosphate potassium and sodium. Laboratory parameters were graded according to NCI-CTCAE version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Any worst case post baseline increase in grade along with any increase to a maximum grade of 3 and a maximum grade of 4 are presented.
Part 2 - Number of Participants With AEs and SAEs Up to approximately 178 weeks An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function.
Part 2 - Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters Baseline (Day 1) and up to approximately 178 weeks Blood samples were collected for the analysis of following hematology parameters: hemoglobin, White blood cell (WBC) count, lymphocytes, neutrophils and platelet. The laboratory parameters were graded according to NCI-CTCAE version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Any worst case post baseline increase in grade along with any increase to a maximum grade of 3 and a maximum grade of 4 are presented.
Part 2 - Changes From Baseline in Urine Specific Gravity Baseline (Day 1) and until end of treatment (up to 178 weeks) Urine samples were collected from participants to assess urine specific gravity. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date
Part 2 - Changes From Baseline in Urine pH Baseline (Day 1) and until end of treatment (up to 178 weeks) Urine samples were collected from participants to assess urine pH levels. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Part 2 - Number of Participants With Worst-case Grade Change From Baseline in Vital Signs: DBP and SBP Baseline (Day 1) and up to approximately 178 weeks DBP and SBP were measured after resting for at least 5 minutes in a supine or semi-recumbent position. They were graded according to NCI-CTCAE version 4.0. For SBP: Grade 0 (\<=120 millimeter of mercury \[mmHg\]), Grade 1 (121-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (\>=160 mmHg). For DBP: Grade 0 (\<=80 mmHg), Grade 1 (81-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (\>=100 mmHg). Higher grade indicates greater severity. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. An increase is defined as an increase in grade relative to Baseline grade. Data for worst-case post Baseline with any grade increase and a maximum post-baseline grade increase to Grade 3 from their baseline grade are presented.
Part 2 - Outcome of First Occurrence of Worsening Eye in BCVA Score Up to approximately 178 weeks The onset of any visual acuity event (change from baseline in logMAR score \>= 0.3 in either eye) was considered resolved if the change from baseline in logMAR score was less than 0.3 in both eyes. Participants with resolved and not resolved outcome of the worsening eye were presented.
Part 2 - Number of Participants With Worst-case Shift From Baseline in Ophthalmological Epithelium Exam Baseline (Day 1) and up to approximately 178 weeks Participants with worst-case shift from baseline in corneal epithelium defects by right eye, left eye and worse eye are presented as normal (N), abnormal (AN) and missing. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Part 2 - Duration of Response Up to approximately 178 weeks Duration of response was defined as the time from first documented evidence of PR or better, to the time when disease progression (PD) is documented per IMWG response criteria; or death due to PD occurs among participants who achieve an overall response, i.e. confirmed PR or better. PD= Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg per 24 h). PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \<200 mg/24 h.
Part 2 - Number of Participants With Worst-case Change Post-baseline in Lab Chemistry Parameters Baseline (Day 1) and up to approximately 178 weeks Blood samples were collected for the analysis of following chemistry parameters: calcium, carbon dioxide, chloride, direct bilirubin, protein, thyrotropin (TSH), thyroxine (T4) and triiodothyronine (T3). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. The summaries of worst case change from baseline with respect to normal range was analyzed for only those laboratory tests that were not gradable by CTCAE version 4.03. The number of participants with decreases to low, changes to normal or no changes from baseline, and increases to high values have been presented.
Part 2 - Number of Participants With Worst-case Change Post-baseline Urinalysis Results Baseline (Day 1) and up to approximately 178 weeks Urine samples were collected to assess urine glucose, protein, occult blood and ketones using dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace, 1+, 2+, 3+ indicating proportional concentrations in the urine sample. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Result for uranalysis parameters were recorded as no change/decreased and any increase. Data for worst-case post baseline are presented.
Part 2 - Number of Participants With Worst-case Change From Baseline in Vital Signs: Pulse Rate and Body Temperature Baseline (Day 1) and up to approximately 178 weeks Vital signs (pulse rate and temperature) were measured after resting for at least 5 minutes in a supine or semi-recumbent position. The abnormal vital sign ranges were: For pulse rate (low \<60 beats per minute \[bpm\] and high \>100 bpm); For body temperature (\<=35 degrees Celsius or \>=38 degrees Celsius). Participants were counted in the worst case category that their value changed to (low, normal or high), unless there was no change in their category. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Part 2 - Number of Participants With Maximum Worst-case Change From Baseline in Best Corrected Visual Acuity Test (BCVA) Scores Baseline (Day 1) and up to approximately 178 weeks BCVA score was calculated based on the Logarithm of the Minimum Angle of Resolution (logMAR score). Any maximum worst-case change from baseline categories are presented for right and left eyes. No change/improved vision is defined as a change from baseline \<0.12; a possible worsened vision is defined as a change from baseline \>=0.12 to \<0.3; a definite worsened vision is defined as a change from baseline \>=0.3 logMAR score. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Part 2 - Time Taken for the Onset of First Occurrence of Worsening in BCVA Score Up to approximately 178 weeks The time for the onset of any visual acuity event (change from baseline logMAR score \>= 0.3 in either eye) was calculated.
Part 2 - Number of Participants According to the Number of Definite Events of Worsening of Vision Up to approximately 178 weeks A definite worsened vision was defined as a change from baseline \>=0.3 logMAR score.
Part 2 - Number of Participants With Resolution of Post Treatment Exposure Worsening in BCVA Score Up to approximately 178 weeks The event was considered resolved if the change from baseline in logMAR score \< 0.3 in both eyes.
Part 2 - Duration of Resolution Post-treatment Exposure of Worsening in BCVA Score Up to approximately 178 weeks The time taken for the resolution of worsening eye post treatment exposure. Duration was defined as the time from onset of any visual acuity event (change from baseline logMAR score \>= 0.3 in either eye) until the event was considered resolved (change from baseline logMAR score \< 0.3 in both eyes). It required at least a one day gap between the resolution of all events from first occurrence to the onset of second occurrence. The end of treatment exposure was defined as 20 days from last infusion date.
Part 2 - Number of Participants With Post-baseline Decline in BCVA to Light Perception or no Light Perception Baseline (Day 1) and up to approximately 178 weeks Part 2 - Progression-free Survival Up to approximately 178 weeks Progression-free survival was defined as the time from first dose until the earliest date of PD per IMWG response criteria, or death due to any cause. PD= Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg per 24 h).
Part 2 - Time to Disease Progression Up to approximately 178 weeks Time to disease progression was defined as the time from first dose until the earliest date of PD per IMWG response criteria, or death due to PD. PD= Increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>= 0.5 g/dL; Serum M-protein increase \>= 1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>= 200 mg per 24 h).
Part 2 - Duration of First Occurrence of Worsening in BCVA Score Up to approximately 178 weeks The time from onset of any visual acuity event (change from baseline logMAR score \>= 0.3 in either eye) until the event is resolved (change from baseline logMAR score \< 0.3 in both eyes) was used to calculate the duration of first occurrence.
Part 2 - Number of Participants With Worst-case Shift From Baseline in Corneal Examinations Baseline (Day 1) and up to approximately 178 weeks Participants with worst-case shift from baseline in corneal examination: corneal ulcer, epithelial microcystic edema, subepithelial haze, corneal neovascularization and microcysts without edema, by right eye (R), left eye (L) and worse eye (W) are presented as yes (Y), no (N) and missing (M). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Part 2 - Number of Participants With Worse Case Post-baseline Punctate Keratopathy Findings Baseline (Day 1) and up to approximately 178 weeks Participants with worse case punctate keratopathy findings post baseline at any ocular exam by right eye, left eye and worse eye are presented as none, mild, moderate and severe. Worse eye indicates the eye with the worst visual acuity. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Part 2 - Number of Participants With Worst-case Shift From Baseline in Lens Examinations Baseline (Day 1) and up to approximately 178 weeks Participants with worst-case shift from baseline in corneal examination which included: clear, pseudophakia, nuclear sclerosis, cortical cataract and posterior subcapsular cataract by right eye, left eye and worse eye are presented as yes (Y), no (N) and missing. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Part 2 - Percentage of Participants With Clinical Benefit Rate Up to approximately 178 weeks Clinical benefit rate was defined as the percentage of participants with a confirmed minimal response (MR) or better according to the IMWG Response Criteria. MR is \>= 25% but \< 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%.
Part 2 - Time to Response Up to approximately 178 weeks Time to response (TTR) was defined as the time between the date of first dose and the first documented evidence of response (PR or better) among participants who achieved a confirmed response of PR or better.
Part 2 - Time to Best Response Up to approximately 178 weeks Time to best response was defined as the time between the date of first dose and the first best documented response (PR or better) among participants who achieved a confirmed response of PR or better.
Part 2 - Cmax for Belantamab Mafodotin After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - End of Infusion Concentration (C-EOI) for Belantamab Mafodotin EOI post belantamab mafodotin dose on Day 1 of each 21 day Cycle till Cycle 11 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - C-EOI for Belantamab Mafodotin EOI post belantamab mafodotin dose on Day 1 of each 21 day Cycle till Cycle 11 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - Time of Cmax (Tmax) for Belantamab Mafodotin After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - Overall Survival Up to approximately 178 weeks Overall Survival was defined as the time from first dose until death due to any cause.
Part 1 - Maximum Concentration (Cmax) for Belantamab Mafodotin After First Dose Pre-dose, end of infusion (EOI), 2, 4, 9, and 24 h post-SOI (start of infusion) on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for Pharmacokinetic (PK) analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - Trough Concentration Prior to the Next Dose for Each Cycle (Ctrough) for Belantamab Mafodotin Pre-dose on Day 1 of each 21 day cycle from Cycle 1 until Cycle 13 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. Ctrough was calculated as the observed concentration at the end of a dosing interval, immediately before next study drug administration on Day 1 of each Cycle. PK parameter was determined using standard non-compartmental methods.
Part 2 - Tmax for Belantamab Mafodotin After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - Tlast for Belantamab Mafodotin After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - Area Under Plasma Concentration-time Curve (AUC) From Time 0 to End of the Dosing Interval [AUC (0-tau)] for Belantamab Mafodotin After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - AUC (0-tau) for Belantamab Mafodotin After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - Cmax for Total mAb After First Dose Pre-dose, EOI, 2, 4, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - C-EOI for Total mAb EOI post belantamab mafodotin dose on Day 1 of Cycle 1, Cycle 2, and Cycle 5 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - Ctrough for Belantamab Mafodotin Pre-dose on Day 1 of each 21 day cycle from Cycle 1 until Cycle 13 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. Ctrough was calculated as the observed concentration at the end of a dosing interval, immediately before next study drug administration on Day 1 of each Cycle. PK parameter was determined using standard non-compartmental methods.
Part 1 - Cmax for Total Monoclonal Antibody (mAb) After First Dose Pre-dose, EOI, 2, 4, 9, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) for Belantamab Mafodotin After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - C-EOI for Total mAb EOI post belantamab mafodotin dose on Day 1 of Cycle 1, Cycle 2, Cycle 5, Cycle 8, and Cycle 11 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - Tmax for Total mAb After First Dose Pre-dose, EOI, 2, 4, 9, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - Tmax for Total mAb After First Dose Pre-dose, EOI, 2, 4, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - Ctrough for Total mAb Cycle 1, Cycle 4, Cycle 7, Cycle 10, and Cycle 13 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. Ctrough was calculated as the observed concentration at the end of a dosing interval, immediately before next study drug administration on Day 1 of each Cycle. PK parameter was determined using standard non-compartmental methods.
Part 1 - Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) for Total mAb After First Dose Pre-dose, EOI, 2, 4, 9, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods. Tlast is the time of last observed quantifiable concentration of belantamab mafodotin in Cycle 1 which extended beyond protocol defined duration for some participants across treatment groups.
Part 2 - Tlast for Total mAb After First Dose Pre-dose, EOI, 2, 4, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods. Tlast is the time of last observed quantifiable concentration of belantamab mafodotin in Cycle 1 which extended beyond protocol defined duration for some participants across treatment groups.
Part 2 - AUC (0-tau) for Total mAb After First Dose Pre-dose, EOI, 2, 4, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - Ctrough for Total mAb Cycle 1 and Cycle 4 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. Ctrough was calculated as the observed concentration at the end of a dosing interval, immediately before next study drug administration on Day 1 of each Cycle. PK parameter was determined using standard non-compartmental methods.
Part 1 - AUC (0-tau) for Total mAb After First Dose Pre-dose, EOI, 2, 4, 9, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - Cmax for Cysteine Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) After First Dose Pre-dose, EOI, 2, 4, 9, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - Cmax for Cys-mcMMAF After First Dose Pre-dose, EOI, 2, 4, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - C-EOI for Cys-mcMMAF After First Dose EOI post belantamab mafodotin dose on Day 1 of Cycle 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - C-EOI for Cys-mcMMAF After First Dose EOI post belantamab mafodotin dose on Day 1 of Cycle 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - Tmax for Cys-mcMMAF After First Dose Pre-dose, EOI, 2, 4, 9, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods. Tlast is the time of last observed quantifiable concentration of belantamab mafodotin in Cycle 1 which extended beyond protocol defined duration for some participants across treatment groups.
Part 1 - Cmax for Pembrolizumab After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - AUC From Time 0 to 168 h After Dosing [AUC (0-168h)] for Cys-mcMMAF After First Dose Pre-dose, EOI, 2, 4, 9, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, and Cycle 1 Day 8 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - AUC (0-168 h) for Cys-mcMMAF After First Dose Pre-dose, EOI, 2, 4, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, and Cycle 1 Day 8 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - Tmax for Cys-mcMMAF After First Dose Pre-dose, EOI, 2, 4, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods. Tlast is the time of last observed quantifiable concentration of belantamab mafodotin in Cycle 1 which extended beyond protocol defined duration for some participants across treatment groups.
Part 1 - Tlast for Cys-mcMMAF After First Dose Pre-dose, EOI, 2, 4, 9, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods. Tlast is the time of last observed quantifiable concentration of belantamab mafodotin in Cycle 1 which extended beyond protocol defined duration for some participants across treatment groups.
Part 2 - Tlast for Cys-mcMMAF After First Dose Pre-dose, EOI, 2, 4, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods. Tlast is the time of last observed quantifiable concentration of belantamab mafodotin in Cycle 1 which extended beyond protocol defined duration for some participants across treatment groups.
Part 2 - Cmax for Pembrolizumab After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - Tmax for Pembrolizumab After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - Tmax for Pembrolizumab After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - AUC (0-tau) for Pembrolizumab After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 2 - Number of Participants With Post-baseline Positive ADAs Against Belantamab Mafodotin Baseline (Day 1) and until end of treatment (up to 178 weeks) Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers. At the time of primary results posting, there was no participants with positive ADA results. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Part 2 - Titers of ADAs Against Belantamab Mafodotin Baseline (Day 1) and up to approximately 178 weeks Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were to be further tested in screening assay, and positive samples were further to be characterized for antibody titers.
Part 1 - Titers of ADAs Against Belantamab Mafodotin Up to approximately 178 weeks Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were to be further tested in screening assay, and positive samples were further to be characterized for antibody titers.
Part 2 - AUC (0-tau) for Pembrolizumab After First Dose Pre-dose, EOI, 2, 4, 9, and 24 h post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, Cycle 1 Day 8, and pre-dose on Cycle 2 Day 1 Blood samples were collected for PK analysis of belantamab mafodotin when administered intravenously in combination with pembrolizumab. PK parameter was determined using standard non-compartmental methods.
Part 1 - Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin Baseline (Day 1) and until end of treatment (up to 178 weeks) Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers. At the time of primary results posting, there was no participants with positive ADA results. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date.
Trial Locations
- Locations (1)
GSK Investigational Site
🇪🇸Salamanca, Spain