Last updated: 03/15/2024 11:10:14

Study evaluating safety, tolerability and clinical activity of GSK2857916 in combination with pembrolizumab in subjects with relapsed/refractory multiple myeloma (RRMM)DREAMM 4

GSK study ID
205207
See study documents
Clinicaltrials.gov ID
NCT03848845
See results summary
EudraCT ID
2018-002816-29
EU CT Number
Not applicable
Trial status
Completed
Completed
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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)
Trial description: 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).
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Part 1: Percentage of subjects with adverse events (AEs) and serious adverse events (SAEs)

Timeframe: Up to 2 years

Part 1: Number of subjects with abnormal hematology parameters

Timeframe: Up to 2 years

Part 1: Number of subjects with abnormal clinical chemistry parameters

Timeframe: Up to 2 years

Part 1: Number of subjects with abnormal urinalysis results

Timeframe: Up to 2 years

Part 1: Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP)

Timeframe: Up to 2 years

Part 1: Number of subjects with abnormal pulse rate

Timeframe: Up to 2 years

Part 1: Number of subjects with abnormal body temperature

Timeframe: Up to 2 years

Part 1: Number of subjects with dose limiting toxicities (DLTs)

Timeframe: Up to 21 days

Part 2: Overall Response Rate

Timeframe: Up to 2 years

Secondary outcomes:

Part 1: Overall response rate

Timeframe: Up to 2 years

Part 1: AUC (0-tau) for total monoclonal antibody (mAb) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose

Timeframe: Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 of Cycle 1 (Each Cycle will be of 21 days)

Part 1: AUC (0-168 hours [h]) for cysteine maleimidocaproyl monomethyl auristatin F (cys-mcMMAF) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose

Timeframe: Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 of Cycle 1 (Each Cycle will be of 21 days)

Part 1: Maximum concentration (Cmax) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose

Timeframe: Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 of Cycle 1 (Each Cycle will be of 21 days)

Part 1: Time of Cmax (tmax) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose

Timeframe: Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 of Cycle 1 (Each Cycle will be of 21 days)

Part 1: Last time point where the concentration is above the limit of quantification (tlast) following IV administration of GSK2857916 in combination with pembrolizumab after the first dose

Timeframe: Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 of Cycle 1 (Each Cycle will be of 21 days)

Part 1: Concentration at trough (Ctrough) following IV administration of GSK2857916 in combination with pembrolizumab for Cycles 2 and 5

Timeframe: Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 and pembrolizumab of Cycles 2 and 5 (Each Cycle will be of 21 days)

Part 1: Ctrough following IV administration of GSK2857916 for Cycles 8 and 11

Timeframe: Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 of Cycles 8 and 11 (Each Cycle will be of 21 days)

Part 1: Ctrough following IV administration of GSK2857916 for Cycle 14 and every 3 Cycles until Cycle 35

Timeframe: Pre-dose (prior to start of infusion) after GSK2857916 of Cycles 14 and every 3 Cycles until Cycle 35 (Each Cycle will be of 21 days)

Part 1: End of infusion concentration following IV administration of GSK2857916 in combination with pembrolizumab

Timeframe: Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 and pembrolizumab of Cycles 2, 5, 8, 11, 14 and every 3 Cycles until Cycle 35 (Each cycle will be of 21 days)

Part 1: Number of subjects with positive anti-drug antibodies (ADAs) against GSK2857916

Timeframe: Up to 2 years

Part 1: Titers of ADAs against GSK2857916

Timeframe: Up to 2 years

Part 2: Number of subjects with AEs and SAEs

Timeframe: Up to 2 years

Part 2: Number of subjects with abnormal hematology parameters

Timeframe: Up to 2 years

Part 2: Number of subjects with abnormal clinical chemistry parameters

Timeframe: Up to 2 years

Part 2: Number of subjects with abnormal urinalysis results

Timeframe: Up to 2 years

Part 2: Number of subjects with abnormal SBP and DBP

Timeframe: Up to 2 years

Part 2: Number of subjects with abnormal pulse rate

Timeframe: Up to 2 years

Part 2: Number of subjects with abnormal body temperature

Timeframe: Up to 2 years

Part 2: Number of subjects with ocular findings on ophthalmic exam

Timeframe: Up to 2 years

Part 2: Clinical benefit rate

Timeframe: Up to 2 years

Part 2: Duration of response

Timeframe: Up to 2 years

Part 2: Time to response

Timeframe: Up to 2 years

Part 2: Time to best response

Timeframe: Up to 2 years

Part 2: Progression-free survival

Timeframe: Up to 2 years

Part 2: Time to disease progression

Timeframe: Up to 2 years

Part 2: Overall Survival

Timeframe: Up to 2 years

Part 2: AUC (0-tau) for total mAb following IV administration of GSK2857916 in combination with pembrolizumab after the first dose

Timeframe: Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 of Cycle 1 (Each Cycle will be of 21 days)

Part 2: AUC (0-168 h) for cys-mcMMAF following IV administration of GSK2857916 in combination with pembrolizumab after the first dose

Timeframe: Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 of Cycle 1 (Each Cycle will be of 21 days)

Part 2: Cmax following IV administration of GSK2857916 in combination with pembrolizumab after the first dose

Timeframe: Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 of Cycle 1 (Each Cycle will be of 21 days)

Part 2: tmax following IV administration of GSK2857916 in combination with pembrolizumab after the first dose

Timeframe: Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 of Cycle 1 (Each Cycle will be of 21 days)

Part 2: Tlast following IV administration of GSK2857916 in combination with pembrolizumab after the first dose

Timeframe: Pre-dose (prior to start of infusion), end of infusion after GSK2857916 and pembrolizumab; 4, 9 or 24 hours after GSK2857916 start of infusion of Cycle 1 Day 1; Anytime on Day 4, Anytime between Days 8 of Cycle 1 (Each Cycle will be of 21 days)

Part 2: Ctrough following IV administration of GSK2857916 in combination with pembrolizumab for Cycles 2 and 5

Timeframe: Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 and pembrolizumab of Cycles 2 and 5 (Each Cycle will be of 21 days)

Part 2: Ctrough following IV administration of GSK2857916 for Cycles 8 and 11

Timeframe: Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 of Cycles 8 and 11 (Each Cycle will be of 21 days)

Part 2: Ctrough following IV administration of GSK2857916 for Cycle 14 and every 3 Cycles until Cycle 35

Timeframe: Pre-dose (prior to start of infusion) after GSK2857916 of Cycle 14 and every 3 Cycles until Cycle 35 (Each Cycle will be of 21 days)

Part 2: End of infusion concentration following IV administration of GSK2857916 in combination with pembrolizumab

Timeframe: Pre-dose (prior to start of infusion) and end of infusion after GSK2857916 and pembrolizumab of Cycles 2, 5, 8, 11, 14 and every 3 Cycles until Cycle 35 (Each cycle will be of 21 days)

Part 2: Number of subjects with positive ADAs against GSK2857916

Timeframe: Up to 2 years

Part 2: Titers of ADAs against GSK2857916

Timeframe: Up to 2 years

Interventions:
Drug: belantamab mafodotin
Drug: Pembrolizumab
Enrollment:
41
Observational study model:
Not applicable
Primary completion date:
2021-18-10
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Multiple Myeloma
Product
Not applicable
Collaborators
Merck
Study date(s)
March 2019 to June 2023
Type
Interventional
Phase
1/2

Participation criteria

Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
  • 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).
  • A subject will NOT be eligible for inclusion in this study if any of the following criteria
  • apply:
Inclusion and exclusion criteria
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

Trial location(s)

Location
Status
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Location
GSK Investigational Site
Atlanta, Georgia, United States, 30322
Status
Study Complete
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Location
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2M9
Status
Study Complete
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Location
GSK Investigational Site
Pozuelo de Alarcón/Madrid, Spain, 28223
Status
Study Complete
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Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
Status
Study Complete
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Location
GSK Investigational Site
Badalona, Spain, 08916
Status
Study Complete
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Location
GSK Investigational Site
Calgary, Alberta, Canada, T2N 2T9
Status
Study Complete
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Location
GSK Investigational Site
Hamburg, Hamburg, Germany, 20246
Status
Study Complete
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Location
GSK Investigational Site
Salamanca, Spain, 37007
Status
Study Complete
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Location
GSK Investigational Site
Madison, Wisconsin, United States, 53792
Status
Study Complete
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Location
GSK Investigational Site
Berlin, Berlin, Germany, 12200
Status
Study Complete
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Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
Status
Study Complete
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Location
GSK Investigational Site
Charlotte, North Carolina, United States, 28204
Status
Study Complete
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Study documents

Protocol
Available language(s): English
Download document(s)
Statistical analysis plan
Available language(s): English
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If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status
Completed
Actual primary completion date
2021-18-10
Actual study completion date
2023-14-06

Plain language summaries

Summary of results in plain language
Available language(s): English, German, Spanish
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To view plain language summaries on trialsummaries.com click here.

Additional information about the trial

Additional information
Not applicable
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