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Multiple MyelomaPhase 1/2DREAMM 4NCT03848845

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

A Phase 1/2 study testing belantamab mafodotin and Pembrolizumab in people with Multiple Myeloma, run by GlaxoSmithKline at 12 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
belantamab mafodotin and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
12 sitesin 4 countries
Study dates
14 Mar 2019to 14 Jun 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

12 sites in 4 countries.

12 sites in 4 countries

United States4 sites

  • GSK Investigational Site

    Atlanta, Georgia, 30322

  • GSK Investigational Site

    Charlotte, North Carolina, 28204

  • GSK Investigational Site

    Indianapolis, Indiana, 46202

  • GSK Investigational Site

    Madison, Wisconsin, 53792

Other trials in United States

Germany3 sites

  • GSK Investigational Site

    Berlin, 12200

  • GSK Investigational Site

    Hamburg, 20246

  • GSK Investigational Site

    Hanover, Lower Saxony, 30625

Other trials in Germany

Spain3 sites

  • GSK Investigational Site

    Badalona, 08916

  • GSK Investigational Site

    Pozuelo de Alarcón/Madrid, 28223

  • GSK Investigational Site

    Salamanca, 37007

Other trials in Spain

Canada2 sites

  • GSK Investigational Site

    Calgary, Alberta, T2N 2T9

  • GSK Investigational Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase I/II Single Arm Open-Label Study to Explore Safety and Clinical Activity of GSK2857916 Administered in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Multiple Myeloma (DREAMM 4)

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).

Being tested
belantamab mafodotin, Pembrolizumab
Keywords
GSK2857916, Pembrolizumab, Multiple Myeloma, RP2D
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • belantamab mafodotinDrug

    belantamab mafodotin will be available as 20 milligrams per millilitre (mg/mL) solution for IV infusion, supplied as frozen liquid. belantamab mafodotin solution will be diluted in normal 0.9% saline to the appropriate concentration for the dose.

  • PembrolizumabDrug

    Pembrolizumab will be available as 100 mg/4 mL solution that should be stored under refrigeration at 2-8 degree Celsius. Pembrolizumab injection (solution) will be diluted prior to IV administration in 0.9% sodium chloride injection or 5% dextrose injection.

Study groups in NCT03848845
Study groupRoleWhat they receive
Part 1: Dose escalationExperimentalSubjects 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.
Receives: Drug: belantamab mafodotin; Drug: Pembrolizumab
Part 2: Expansion cohortExperimentalSubjects 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.
Receives: Drug: belantamab mafodotin; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to approximately 31 months

  2. 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.

    Measured: Up to 21 days

  3. 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.

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

  4. 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.

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

  5. 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.

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

  6. 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.

    Measured: Baseline (Day 1) and up to 31 months

  7. 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.

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

  8. 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.

    Measured: Baseline (Day 1) and Week 46

  9. 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.

    Measured: Baseline (Day 1) and Week 46

  10. 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.

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

  11. 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.

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

  12. 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.

    Measured: Up to approximately 31 months

Secondary outcomes (74)

  1. 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.

    Measured: Up to approximately 178 weeks

  2. Part 2 - Number of Participants With AEs and 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.

    Measured: Up to approximately 178 weeks

  3. 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.

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

  4. 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.

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

  5. 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.

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

  6. 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.

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

  7. 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.

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

  8. 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

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

  9. 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.

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

  10. 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.

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

  11. 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.

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

  12. 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.

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

  13. 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.

    Measured: Up to approximately 178 weeks

  14. 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.

    Measured: Up to approximately 178 weeks

  15. 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.

    Measured: Up to approximately 178 weeks

  16. Part 2 - Number of Participants According to the Number of Definite Events of Worsening of Vision

    A definite worsened vision was defined as a change from baseline >=0.3 logMAR score.

    Measured: Up to approximately 178 weeks

  17. Part 2 - Number of Participants With Resolution of Post Treatment Exposure Worsening in BCVA Score

    The event was considered resolved if the change from baseline in logMAR score < 0.3 in both eyes.

    Measured: Up to approximately 178 weeks

  18. 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.

    Measured: Up to approximately 178 weeks

  19. Part 2 - Number of Participants With Post-baseline Decline in BCVA to Light Perception or no Light Perception

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

  20. 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.

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

  21. 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.

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

  22. 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.

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

  23. 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.

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

  24. 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%.

    Measured: Up to approximately 178 weeks

  25. 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.

    Measured: Up to approximately 178 weeks

  26. 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.

    Measured: Up to approximately 178 weeks

  27. 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.

    Measured: Up to approximately 178 weeks

  28. 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).

    Measured: Up to approximately 178 weeks

  29. 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).

    Measured: Up to approximately 178 weeks

  30. Part 2 - Overall Survival

    Overall Survival was defined as the time from first dose until death due to any cause.

    Measured: Up to approximately 178 weeks

  31. 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.

    Measured: 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

  32. Part 2 - Cmax for Belantamab Mafodotin 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.

    Measured: 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

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

    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.

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

  34. Part 2 - C-EOI for Belantamab Mafodotin

    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.

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

  35. Part 1 - Time of Cmax (Tmax) for Belantamab Mafodotin 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.

    Measured: 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

  36. Part 2 - Tmax for Belantamab Mafodotin 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.

    Measured: 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

  37. 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.

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

  38. Part 2 - 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.

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

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

    Measured: 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

  40. Part 2 - Tlast for Belantamab Mafodotin 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.

    Measured: 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

  41. 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

    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.

    Measured: 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

  42. Part 2 - AUC (0-tau) for Belantamab Mafodotin 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.

    Measured: 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

  43. Part 1 - Cmax for Total Monoclonal Antibody (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.

    Measured: 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

  44. Part 2 - Cmax 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.

    Measured: 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

  45. Part 1 - C-EOI for Total mAb

    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.

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

  46. Part 2 - C-EOI for Total mAb

    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.

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

  47. Part 1 - Tmax 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.

    Measured: 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

  48. Part 2 - Tmax 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.

    Measured: 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

  49. Part 1 - Ctrough for Total mAb

    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.

    Measured: Cycle 1, Cycle 4, Cycle 7, Cycle 10, and Cycle 13

  50. Part 2 - Ctrough for Total mAb

    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.

    Measured: Cycle 1 and Cycle 4

  51. 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.

    Measured: 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

  52. Part 2 - 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.

    Measured: 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

  53. Part 1 - AUC (0-tau) 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.

    Measured: 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

  54. Part 2 - AUC (0-tau) 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.

    Measured: 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

  55. Part 1 - Cmax for Cysteine Maleimidocaproyl Monomethyl Auristatin F (Cys-mcMMAF) 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.

    Measured: 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

  56. Part 2 - Cmax for Cys-mcMMAF 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.

    Measured: 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

  57. Part 1 - C-EOI for Cys-mcMMAF 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.

    Measured: EOI post belantamab mafodotin dose on Day 1 of Cycle 1

  58. Part 2 - C-EOI for Cys-mcMMAF 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.

    Measured: EOI post belantamab mafodotin dose on Day 1 of Cycle 1

  59. Part 1 - Tmax for Cys-mcMMAF 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.

    Measured: 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

  60. Part 2 - Tmax for Cys-mcMMAF 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.

    Measured: 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

  61. Part 1 - Tlast for Cys-mcMMAF 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.

    Measured: 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

  62. Part 2 - Tlast for Cys-mcMMAF 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.

    Measured: 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

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

    Measured: 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

  64. Part 2 - AUC (0-168 h) for Cys-mcMMAF 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.

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

  65. Part 1 - Cmax for Pembrolizumab 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.

    Measured: 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

  66. Part 2 - Cmax for Pembrolizumab 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.

    Measured: 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

  67. Part 1 - Tmax for Pembrolizumab 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.

    Measured: 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

  68. Part 2 - Tmax for Pembrolizumab 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.

    Measured: 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

  69. Part 1 - AUC (0-tau) for Pembrolizumab 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.

    Measured: 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

  70. Part 2 - AUC (0-tau) for Pembrolizumab 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.

    Measured: 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

  71. 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.

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

  72. Part 2 - Number of Participants With Post-baseline Positive 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.

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

  73. 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.

    Measured: Up to approximately 178 weeks

  74. Part 2 - 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2019
  2. Study start14 Mar 2019
  3. Primary completion18 Oct 2021
  4. Study completion14 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Subjects will receive GSK2857916 at escalating doses along with pembrolizumab on Day 1 of each 21-day Cycle to establish RP2D during the Part 1 of the study. Subjects will receive GSK2857916 at RP2D along with pembrolizumab on Day 1 of each 21-day Cycle in Part 2 of the study.
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03848845
Sponsor's protocol ID
205207
Other IDs
KEYNOTE PN489, 2018-002816-29, 2018
Acronym
DREAMM 4
Status last verified
Mar 2024
First submitted
19 Feb 2019
Last updated
9 Apr 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • Suvannasankha A, Bahlis N, Trudel S, Weisel K, Koenecke C, Oriol A, Voorhees PM, Alonso AA, Callander NS, Mateos MV, Reddy N, Hakim S, LaMacchia J, Patel N, Williams D, Jewell RC, Zhou X, Gupta I, Opalinska J, Nooka AK. Safety and efficacy of belantamab mafodotin with pembrolizumab in patients with relapsed or refractory multiple myeloma. Cancer. 2024 Aug 1;130(15):2629-2641. doi: 10.1002/cncr.35319. Epub 2024 Apr 17.

    PubMed 38630908

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing belantamab mafodotin and Pembrolizumab in people with Multiple Myeloma, run by GlaxoSmithKline at 12 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, Germany, Spain, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 - Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Up to approximately 31 months). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03848845, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2024.

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