Clinical Trials Register

Summary
EudraCT Number:	2017-004689-93
Sponsor's Protocol Code Number:	207497
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-08-06
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2017-004689-93

A.3

Full title of the trial

A Phase I/II, Open-label, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-Drug Conjugate GSK2857916 Administered in Combination with Lenalidomide Plus
Dexamethasone (Arm A), or Bortezomib Plus Dexamethasone (Arm B) in Participants with Relapsed / Refractory Multiple Myeloma – DREAMM 6

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

study to evaluate the safety of the study drug, GSK2857916, at different doses and how well it works to treat people with multiple myeloma when taken together with Lenalidomide Plus Dexamethasone (Arm A), or Bortezomib Plus Dexamethasone (Arm B).

A.3.2

Name or abbreviated title of the trial where available

GSK 207497 DREAMM 6

A.4.1

Sponsor's protocol code number

207497

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03544281

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Research & Development Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Research & Development Ltd
B.5.2	Functional name of contact point	GSK Clinical Support Help Desk
B.5.3	Address:
B.5.3.1	Street Address	980 Great West Road
B.5.3.2	Town/ city	Brentford, Middlesex
B.5.3.3	Post code	TW8 9GS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 800 783 9733
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/077/17
D.3 Description of the IMP
D.3.1	Product name	Belantamab Mafodotin
D.3.2	Product code	GSK2857916
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Belantamab Mafodotin
D.3.9.2	Current sponsor code	GSK2857916
D.3.9.3	Other descriptive name	Belantamab Mafodotin
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Relapsed / Refractory Multiple Myeloma

E.1.1.1

Medical condition in easily understood language

Multiple Myeloma

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10028228
E.1.2	Term	Multiple myeloma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Dose Escalation: Determine safety, tolerability of belantamab mafodotin in combination with either Len/Dex (Arm A) or Bor/Dex (Arm B) to establish a recommended dose range and schedule to evaluate in Dose Expansion for participants with RRMM

Dose Escalation and Expansion: Select the dose(s) and dosing schedule for further investigation based on safety and tolerability of belantamab mafodotin in combination with either Len/Dex (Arm A) or Bor/Dex (Arm B) for participants with RRMM

Dose Expansion
To determine preliminary clinical activity of belantamab mafodotin in combination with either Len/Dex (Arm A) or Bor/Dex (Arm B) for participants with RRMM

E.2.2

Secondary objectives of the trial

- To evaluate the pharmacokinetics profile of belantamab mafodotin when administered in combination with Len/Dex (Arm A) or Bor/Dex (Arm B) in participants with RRMM
- To evaluate the pharmacokinetics profile of lenalidomide when administered in combination with belantamab mafodotin and dexamethasone
- To evaluate the pharmacokinetics profile of bortezomib when administered in combination with belantamab mafodotin and dexamethasone
- To assess anti-drug antibodies (ADAs) against belantamab mafodotin
- To evaluate the effect and tolerability of belantamab mafodotin in combination with Len/Dex (Arm A) or Bor/Dex (Arm B) on symptomatic adverse events in participants with RRMM
- To further characterize safety of belantamab mafodotin administered in combination with Len/Dex (Arm A) or Bor/Dex (Arm B) in participants with RRMM
- To evaluate the effect of belantamab mafodotin in combination with Len/Dex(Arm A) or Bor/Dex (ArmB) on health-related quality of life in participants with RRMM

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Male or female, 18 years or older (at the time consent is obtained).
3. Have confirmed diagnosis of Multiple Myeloma as defined by the International Myeloma Working Group (IMWG)[Rajkumar, 2016].
4. Eastern Cooperative Oncology Group (ECOG) performance status:
 -For Arm A only: 0 to 1 (Appendix 3, Section 13.3 in the Protocol).
 -For Arm B only: 0 to 2 (Appendix 3, Section 13.3 in the Protocol).
5. Have undergone autologous SCT or are considered transplant ineligible.
6. Have been previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy.
7. Must have at least ONE aspect of measurable disease, defined as one of the following:
a. Urine M-protein excretion ≥200 mg/24h, or
b. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or
c. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL
(≥100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65).
8. Participants with a history of autologous stem cell transplant (SCT) are eligible for study participation provided the following eligibility criteria are met:
a. Autologous SCT was >100 days prior to study enrollment
b. No active bacterial, viral, or fungal infection(s) present
c. Participant meets the remainder of the eligibility criteria outlined in this protocol
9. 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 enrollment, except for alopecia. Participants with Grade 2 neuropathy can be enrolled into Len/Dex treatment arm, but not into Bor/Dex treatment arm.
10. Adequate organ system functions as defined by laboratory assessments listed in Table 13 in the Protocol.

(For Inclusion Criteria related with Female and Male Participants
Contraception, please refer to the Protocol)

Additional Inclusion Criteria for WOCBP Participants Assigned to Arm A Due to lenalidomide being a thalidomide analogue with risk for embryofetal toxicity and prescribed under a pregnancy prevention/controlled distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control (one method that is highly effective), beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide treatment. Thereafter, WOCBP participants must use a contraceptive method that is highly effective (with a failure rate of <1% per year) for a further 3 months, and agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period.
Two negative pregnancy tests must be obtained prior to initiating lenalidomide therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing lenalidomide therapy.

Additional Inclusion Criteria for WOCBP Participants Assigned to Arm B WOCBP assigned to Arm B must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1 and agree to use effective contraception during the study and for 4 months after the last dose of belantamab mafodotin or 7 months from the last dose of bortezomib, whichever is longer.

E.4

Principal exclusion criteria

1. Systemic anti-myeloma therapy (including systemic steroids) within ≤ 14 days, or plasmapheresis within 7 days prior to the first dose of study drug.
2. Use of an investigational drug within 14 days or five half-lives (whichever is longer) preceding the first dose of study drug.
3. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs.
4. Prior allogenic stem cell transplant.
Note: Participants who have undergone syngeneic transplant will be allowed only if they have no history and no currently active, graft versus host disease (GvHD)
5. Evidence of active mucosal or internal bleeding.
6. Any major surgery within the last four weeks.
7. Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfill criteria given in Table 8 in the Protocol
8. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures.
9. Current active liver or biliary disease (with the exception of Gilbert’s syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease per investigator’s assessment).
10. Participants with invasive malignancies other than multiple myeloma
are excluded, unless the second malignancy has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease.
Note: Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction.
11. Evidence of cardiovascular risk including any of the following:
a. Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block.
b. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening.
c. Class III or IV heart failure as defined by the New York Heart Association functional classification system (Appendix 5, Section 13.5 in the Protocol).
d. Uncontrolled hypertension.
12. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
13. Pregnant or lactating female.
14. Active infection requiring treatment.
15. Known HIV infection.
16. 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)
17. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing
18. Current corneal disease except for mild punctate keratopathy (Appendix 8, Section 13.8 in the Protocol). Note: Participants with mild punctate keratopathy are allowed.

Additional Exclusion Criteria for Participants Assigned to Arm A
(belantamab mafodotin plus Len/Dex)
19. Participants unable to tolerate antithrombotic prophylaxis must be excluded.
20. Discontinuation of prior treatment with lenalidomide due to intolerable adverse events.

Additional Exclusion Criteria for Participants Assigned to Arm B
(belantamab mafodotin plus Bor/Dex)
21. Unacceptable adverse effects from previous bortezomib treatment.
22. Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain from previous bortezomib treatment.
23. Intolerance or contraindications to anti-viral prophylaxis

E.5 End points

E.5.1

Primary end point(s)

Dose Escalation
Number (%) of participants with dose-limiting toxicities (DLTs).
Number (%) of participants with adverse events (AEs), changes in clinical signs and laboratory parameters.

Dose Escalation and Expansion
A comprehensive determination based on safety and SAE/AEs.

Dose Expansion
A specific determination based on ORR defined as percentage (%) of participants achieving >= PR as defined by the IMWG Uniform Response Criteria for MM [Kumar,2016].

E.5.1.1

Timepoint(s) of evaluation of this end point

Please refer to the Protocol

E.5.2

Secondary end point(s)

- belantamab mafodotin PK parameters, as data permit
- Lenalidomide PK parameters, as data permit in Cycle 1
- Bortezomib PK parameters, as data permit in Cycle 1
- Incidence and titers of ADAs against belantamab mafodotin pre-dose in Cycle 1 and selected subsequent cycles
- Changes from baseline in symptoms and related impacts as measured by OSDI, NEIVFQ-25 and PRO CTCAE
- Incidence of AEs, including SAEs and AEs of special interest (corneal events, thrombocytopenia and infusion related reactions).
- Ocular findings on ophthalmic exam
- Changes from baseline in health-related quality of life as measured by the EORTC QLQ-C30 AND QLQ-MY20

E.5.2.1

Timepoint(s) of evaluation of this end point

Please refer to the Protocol.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

tolerability

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

France

Spain

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

A participant will be considered to have completed the study if he or she received at least one dose of study treatment and has progressed or died before the end of the study, has not been lost to Follow-up, or has not withdrawn consent, or the study or a treatment arm has been
terminated.
A participant will be considered to have withdrawn from the study if
- has not died and is lost to Follow-up, or
- has withdrawn consent, or
- is no longer being followed at the investigator's discretion

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1