Study Evaluating Safety, Tolerability and Clinical Activity of GSK2857916 in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Multiple Myeloma (RRMM)

GlaxoSmithKline41 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Provide signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Male or female, 18 years or older (at the time consent is obtained). * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Subjects must: have histologically or cytologically confirmed diagnosis of Multiple myeloma (MM), as defined by IMWG, 2014 and has undergone stem cell transplant or is considered transplant ineligible, and has been treated with at least 3 prior lines of prior anti-myeloma treatments including an immunomodulatory imide drug (IMiD) (eg. lenalidomide or pomalidomide), a proteasome inhibitor (eg. bortezomib, ixazomib or carfilzomib) and an anti-CD38 antibody alone or in combination. Line of therapy are defined by consensus panel of the International Myeloma Workshop, Has measurable disease defined as one the following: a) Serum M-protein \>=0.5 grams per deciliter (g/dL) (\>=5 grams per liter \[g/L\]). b) Urine M-protein ≥200 mg/24h. c) Serum Free light chain (FLC) assay: Involved FLC level ≥10 milligrams per deciliter (mg/dL) (≥100 milligrams per liter \[mg/L\]) and an abnormal serum free light chain ratio (\<0.26 or \>1.65). * Subjects with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: a) transplant was \> 100 days prior to study enrolment. b) no active infection(s). c) subject meets the remainder of the eligibility criteria. * Adequate organ system functions as defined by the laboratory assessments. * All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events \[NCI-CTCAE\], version 4.03, 2010) must be \<= Grade 1 at the time of enrolment except for alopecia and Grade 2 neuropathy. * A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), preferably with low user dependency, during the intervention period and for at least 120 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. * Male subjects are eligible to participate if they agree to the following during the intervention period and for at least 140 days after the last dose of study intervention. Male subjects should refrain from donating sperm, plus, either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of \<1% per year when having sexual intercourse with a woman of childbearing potential who is not currently pregnant. Exclusion criteria: A subject will NOT be eligible for inclusion in this study if any of the following criteria apply: * Systemic anti-myeloma therapy or an investigational drug \<=14 days or five half-lives, whichever is shorter, preceding the first dose of study drug * Plasmapheresis within 7 days prior to the first dose of study drug * Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs * Has received prior therapy with an anti-PD-1, anti-Programmed cell death Ligand 1 (PD-L1), or anti-Programmed cell death Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated antigen 4 \[CTLA-4\], OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune related adverse event (irAE) * Current corneal epithelial disease except mild punctate keratopathy * Any major surgery within the last four weeks prior to the first dose of study therapy * Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect subject's safety). Subjects with isolated proteinuria resulting from MM are eligible, provided they fulfil criteria as per adequate organ system function mentioned under inclusion criteria. * Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures. * Has received prior radiotherapy within 2 weeks of start of study therapy. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (\<=2 weeks of radiotherapy) to non-central nervous system (CNS) disease. * History of (non-infectious) pneumonitis that required steroids, or current pneumonitis * Current active liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. * Malignancies other than disease under study are excluded, except for any other malignancy from which the subject has been disease-free for more than 2 years and, in the opinion of the principal investigators and GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (RRMM). Subjects with curatively treated non-melanoma skin cancer are allowed. * Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study therapy * Evidence of cardiovascular risk including any of the following: a) corrected for heart rate by Fridericia's formula (QTcF) interval ≥470 msecs. b) Evidence of current clinically significant uncontrolled arrhythmias; i. including clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block. c) History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening. d) Class III or IV heart failure as defined by the New York Heart Association functional classification system. e) Uncontrolled hypertension. f) Presence of cardiac pacemaker (or defibrillator) with a predominantly ventricular paced rhythm, limiting ECG/QTcF analysis. g) Abnormal cardiac valve morphology (\>=Grade 2) documented by echocardiogram (subjects with grade 1 abnormalities \[i.e., mild regurgitation/stenosis\] can be entered on study). Subjects with moderate valvular thickening should not be entered on study. * Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916 or pembrolizumab, or any of the components of the study treatment. * Pregnant or lactating female. * Known active infection requiring antibiotic, antiviral, or antifungal treatment. * Known Human Immunodeficiency Virus (HIV) infection. * Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of study treatment * Positive hepatitis C antibody test result or positive hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. * Has received a live-virus vaccination within 30 days of planned start of study therapy. * Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other chronic form of immunosuppressive therapy within 7 days prior the first dose of study therapy. * Has known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study. * Has had an allogenic tissue/solid organ transplant

Locations (12)

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Madison, Wisconsin, United States

GSK Investigational Site

Calgary, Alberta, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Berlin, Germany

GSK Investigational Site

Hamburg, Germany

GSK Investigational Site

Badalona, Spain

...and 2 more locations

Outcomes

Primary Outcomes

Part 1 - Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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.

Time frame: Up to approximately 31 months

Part 1 - Number of Participants With Dose Limiting Toxicities (DLTs)

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.

Time frame: Up to 21 days

Part 1 - Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters

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.

Time frame: Baseline (Day 1) and up to approximately 31 months

Part 1 - Number of Participants With Worst-case Change Post-baseline in Hematology Parameters

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.

Time frame: Baseline (Day 1) and up to approximately 31 months

Part 1 - Number of Participants With Worst-case Grade Change From Baseline in Lab Chemistry Parameters

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.

Time frame: Baseline (Day 1) and up to approximately 31 months

Part 1 - Number of Participants With Worst-case Change Post-baseline in Lab Chemistry Parameters

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.

Time frame: Baseline (Day 1) and up to 31 months

Part 1 - Number of Participants With Worst-case Change Post-baseline Urinalysis Results

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.

Time frame: Baseline (Day 1) and up to approximately 31 months

Part 1 - Changes From Baseline in Urine Potential of Hydrogen (pH)

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.

Time frame: Baseline (Day 1) and Week 46

Part 1 - Changes From Baseline in Urine Specific Gravity

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.

Time frame: Baseline (Day 1) and Week 46

Part 1 - Number of Participants With Worst-case Grade Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

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.

Time frame: Baseline (Day 1) and up to approximately 31 months

Part 1 - Number of Participants With Worst-case Change From Baseline in Vital Signs: Pulse Rate and Body Temperature

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.

Time frame: Baseline (Day 1) and up to approximately 31 months

Part 2 - Percentage of Participants With Overall Response Rate (ORR)

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.

Time frame: Up to approximately 31 months

Secondary Outcomes

Part 1 - Percentage of Participants With Overall Response Rate (ORR)

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.

Time frame: Up to approximately 178 weeks

Part 2 - Number of Participants With AEs and SAEs

Time frame: Up to approximately 178 weeks

Part 2 - Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Number of Participants With Worst-case Change Post-baseline in Hematology Parameters

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Number of Participants With Worst-case Grade Change From Baseline in Lab Chemistry Parameters

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Number of Participants With Worst-case Change Post-baseline in Lab Chemistry Parameters

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Number of Participants With Worst-case Change Post-baseline Urinalysis Results

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Changes From Baseline in Urine Specific Gravity

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

Time frame: Baseline (Day 1) and until end of treatment (up to 178 weeks)

Part 2 - Changes From Baseline in Urine pH

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.

Time frame: Baseline (Day 1) and until end of treatment (up to 178 weeks)

Part 2 - Number of Participants With Worst-case Grade Change From Baseline in Vital Signs: DBP and SBP

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Number of Participants With Worst-case Change From Baseline in Vital Signs: Pulse Rate and Body Temperature

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Number of Participants With Maximum Worst-case Change From Baseline in Best Corrected Visual Acuity Test (BCVA) Scores

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Time Taken for the Onset of First Occurrence of Worsening in BCVA Score

The time for the onset of any visual acuity event (change from baseline logMAR score \>= 0.3 in either eye) was calculated.

Time frame: Up to approximately 178 weeks

Part 2 - Outcome of First Occurrence of Worsening Eye in BCVA Score

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.

Time frame: Up to approximately 178 weeks

Part 2 - Duration of First Occurrence of Worsening in BCVA Score

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.

Time frame: Up to approximately 178 weeks

Part 2 - Duration of Resolution Post-treatment Exposure of Worsening in BCVA Score

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.

Time frame: Up to approximately 178 weeks

Part 2 - Number of Participants With Worst-case Shift From Baseline in Ophthalmological Epithelium Exam

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Number of Participants With Worst-case Shift From Baseline in Corneal Examinations

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Number of Participants With Worse Case Post-baseline Punctate Keratopathy Findings

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Number of Participants With Worst-case Shift From Baseline in Lens Examinations

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.

Time frame: Baseline (Day 1) and up to approximately 178 weeks

Part 2 - Percentage of Participants With Clinical Benefit Rate

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%.

Time frame: Up to approximately 178 weeks

Part 2 - Duration of Response

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.

Time frame: Up to approximately 178 weeks

Part 2 - Time to Response

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.

Time frame: Up to approximately 178 weeks

Part 2 - Time to Best Response

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.

Time frame: Up to approximately 178 weeks

Part 2 - Progression-free Survival

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).

Time frame: Up to approximately 178 weeks

Part 2 - Time to Disease Progression

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).

Time frame: Up to approximately 178 weeks

Part 1 - Maximum Concentration (Cmax) for Belantamab Mafodotin After First Dose

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.

Time frame: 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

Part 2 - Cmax for Belantamab Mafodotin After First Dose

Time frame: 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

Part 1 - End of Infusion Concentration (C-EOI) for Belantamab Mafodotin

Time frame: EOI post belantamab mafodotin dose on Day 1 of each 21 day Cycle till Cycle 11

Part 2 - C-EOI for Belantamab Mafodotin

Time frame: EOI post belantamab mafodotin dose on Day 1 of each 21 day Cycle till Cycle 11

Part 1 - Time of Cmax (Tmax) for Belantamab Mafodotin After First Dose

Time frame: 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

Part 2 - Tmax for Belantamab Mafodotin After First Dose

Time frame: 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

Part 1 - Trough Concentration Prior to the Next Dose for Each Cycle (Ctrough) for Belantamab Mafodotin

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.

Time frame: Pre-dose on Day 1 of each 21 day cycle from Cycle 1 until Cycle 13

Part 2 - Ctrough for Belantamab Mafodotin

Time frame: Pre-dose on Day 1 of each 21 day cycle from Cycle 1 until Cycle 13

Part 1 - Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) for Belantamab Mafodotin After First Dose

Time frame: 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

Part 2 - Tlast for Belantamab Mafodotin After First Dose

Time frame: 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

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

Time frame: 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

Part 2 - AUC (0-tau) for Belantamab Mafodotin After First Dose

Time frame: 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

Part 1 - Cmax for Total Monoclonal Antibody (mAb) After First Dose

Time frame: 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

Part 2 - Cmax for Total mAb After First Dose

Time frame: 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

Part 1 - C-EOI for Total mAb

Time frame: EOI post belantamab mafodotin dose on Day 1 of Cycle 1, Cycle 2, Cycle 5, Cycle 8, and Cycle 11

Part 2 - C-EOI for Total mAb

Time frame: EOI post belantamab mafodotin dose on Day 1 of Cycle 1, Cycle 2, and Cycle 5

Part 1 - Tmax for Total mAb After First Dose

Time frame: 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

Part 2 - Tmax for Total mAb After First Dose

Time frame: 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

Part 1 - Ctrough for Total mAb

Time frame: Cycle 1, Cycle 4, Cycle 7, Cycle 10, and Cycle 13

Part 2 - Ctrough for Total mAb

Time frame: Cycle 1 and Cycle 4

Part 1 - Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) for Total mAb After First Dose

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.

Time frame: 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

Part 2 - Tlast for Total mAb After First Dose

Time frame: 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

Part 1 - AUC (0-tau) for Total mAb After First Dose

Time frame: 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

Part 2 - AUC (0-tau) for Total mAb After First Dose

Time frame: 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

Part 1 - Cmax for Cysteine Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) After First Dose

Time frame: 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

Part 2 - Cmax for Cys-mcMMAF After First Dose

Time frame: 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

Part 1 - C-EOI for Cys-mcMMAF After First Dose

Time frame: EOI post belantamab mafodotin dose on Day 1 of Cycle 1

Part 2 - C-EOI for Cys-mcMMAF After First Dose

Time frame: EOI post belantamab mafodotin dose on Day 1 of Cycle 1

Part 1 - Tmax for Cys-mcMMAF After First Dose

Time frame: 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

Part 2 - Tmax for Cys-mcMMAF After First Dose

Time frame: 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

Part 1 - Tlast for Cys-mcMMAF After First Dose

Time frame: 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

Part 2 - Tlast for Cys-mcMMAF After First Dose

Time frame: 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

Part 1 - AUC From Time 0 to 168 h After Dosing [AUC (0-168h)] for Cys-mcMMAF After First Dose

Time frame: 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

Part 2 - AUC (0-168 h) for Cys-mcMMAF After First Dose

Time frame: Pre-dose, EOI, 2, 4, and 24 hour post-SOI on Cycle 1 Day 1, Cycle 1 Day 4, and Cycle 1 Day 8

Part 1 - Cmax for Pembrolizumab After First Dose

Time frame: 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

Part 2 - Cmax for Pembrolizumab After First Dose

Time frame: 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

Part 1 - Tmax for Pembrolizumab After First Dose

Time frame: 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

Part 2 - Tmax for Pembrolizumab After First Dose

Time frame: 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

Part 1 - AUC (0-tau) for Pembrolizumab After First Dose

Time frame: 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

Part 2 - AUC (0-tau) for Pembrolizumab After First Dose

Time frame: 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

Part 1 - Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin

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.

Time frame: Baseline (Day 1) and until end of treatment (up to 178 weeks)

Part 2 - Number of Participants With Post-baseline Positive ADAs Against Belantamab Mafodotin

Time frame: Baseline (Day 1) and until end of treatment (up to 178 weeks)

Part 1 - Titers of ADAs Against Belantamab Mafodotin

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.

Time frame: Up to approximately 178 weeks

Part 2 - Titers of ADAs Against Belantamab Mafodotin

Time frame: Baseline (Day 1) and up to approximately 178 weeks