Presented at the American Society for Clinical Oncology (ASCO) Congress, Virtual Format, May 29–31, 2020

Study population

Eligibility criteria for this study have been previously reported.5

Key inclusion criteria were:

• Age ≥18 years

• Histologically or cytologically confirmed multiple myeloma (International Myeloma Working Group

[IMWG] criteria)8

• Measurable disease (according to serum and/or urine M-protein and/or serum free light chain levels)

• Eastern Cooperative Oncology Group (ECOG) performance status 0–2

• ≥3 prior lines of therapy and refractory to immunomodulatory agents and proteasome inhibitors, and

refractory/intolerant to an anti-CD38 antibody

• Prior autologous stem cell transplantation allowed if >100 days prior to screening and no active infections

• Acceptable hematologic- (neutrophil, hemoglobin and platelet) and vital-organ (liver, heart and kidney) function

Study endpoints

Efficacy endpoints were assessed according to IMWG 2016 criteria9 and included:

• ORR (by independent review committee) • PFS

• Clinical benefit rate (CBR) • Overall survival (OS)

• DoR

• Safety was assessed by adverse events (AEs) and AEs of special interest (AESIs), which were graded by

the investigator according to CTCAE version 4.0310 (with the exception of changes in the corneal

epithelium observed by ophthalmic examination); and rates of discontinuations and dose adjustments.5

Patients with relapsed or refractory multiple myeloma (RRMM) and high-risk (HR) cytogenetics have a poor

prognosis and therefore need effective therapies.1,2

B-cell maturation antigen (BCMA) is a cell membrane receptor that is expressed on all malignant plasma cells

and is essential for their proliferation and survival.3

Belantamab mafodotin (belamaf; GSK2857916) is a first-in-class BCMA-binding, humanized, afucosylated,

monoclonal antibody–drug conjugate.3

Belamaf binds to BCMA and eliminates multiple myeloma cells by a multimodal mechanism of action,

including apoptosis, release of immunogenic cell-death markers, antibody-dependent cell-mediated

cytotoxicity, and antibody-dependent phagocytosis.3,4

In the DREAMM-2 study (NCT03525678), single-agent belamaf demonstrated deep and durable responses

and an acceptable safety profile in patients with heavily pretreated (median of 6–7 prior lines) RRMM.5,6 The

results at 6-month follow-up were:5

• Belamaf 2.5 mg/kg: overall response rate (ORR) 31% (97.5% CI 20.8–42.6); median progression-free

survival (PFS) 2.9 months (95% CI 2.1–3.7); median duration of response was not reached (NR).

• Belamaf 3.4 mg/kg: ORR 34% (97.5% CI 20.8–42.6); median PFS 4.9 months (95% CI 2.3–6.2); median

DoR was NR.

Background

DREAMM-2: Single-Agent Belantamab Mafodotin (GSK2857916) in Patients With

Relapsed/Refractory Multiple Myeloma (RRMM) and High-Risk (HR) Cytogenetics

Poster No. 441

Adam D Cohen1*, Suzanne Trudel2, Sagar Lonial3, Edward Libby4, Hans C Lee5,

Britta Besemer6, Thierry Facon7, Ajay K Nooka3, Natalie Callander8, Ajai Chari9,

Ira Gupta10, Sofia Paul10, Joanna Opalinska10, Paul Richardson11

1Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; 2 Princess Margaret Cancer Centre, Toronto, ON,

Canada; 3Emory University, Winship Cancer Institute, Atlanta, GA, USA; 4Division of Medical Oncology, University of Washington,

Seattle, WA, USA; 5MD Anderson Cancer Center, Houston, TX, USA; 6Universitaetsklinikum Tuebingen, Tuebingen, Germany; 7CHRU de Lille, Hôpital Claude Huriez, Lille, France; 8University of Wisconsin School, Carbone Cancer Center, Madison, WI, USA; 9Icahn School of Medicine at Mount Sinai, New York, NY, USA; 10GlaxoSmithKline, Upper Providence, PA, USA; 11Dana Farber

Cancer Institute, Boston, MA, USA

Results

Conclusions• Single-agent belamaf represents a new treatment option for patients with RRMM, including those with HR cytogenetics.

• Efficacy and safety of single-agent belamaf were similar in patients with HR cytogenetics and in those with SR cytogenetics;

ORR, DoR, and OS were similar to those observed in the overall DREAMM-2 population.5,6

• Patients with HR cytogenetics maintain deep and durable clinical responses with single-agent belamaf, comparable to those

reported in the overall population.5,6

• The safety profile remained consistent with previous reports.5,6

• Further investigation of patients with HR cytogenetics receiving single-agent belamaf is warranted.

• Belamaf is being evaluated in other clinical trials in various combination strategies in various MM settings (oral presentation

no. 8502 and poster nos. 452 & 456). Other analyses of the DREAMM-2 study are also presented in poster nos. 436 & 419.

Details of the DREAMM-2 study design (Figure 1) have been previously published.5 Here, we report

outcomes from HR and standard risk (SR) patient groups in the DREAMM-2 9-month follow-up.

HR and SR patient groups were determined by cytogenetic profile:

• HR – patients with any of t(4;14), t(14;16), 17p13del, or 1q21+.1,7

• SR – patients without any of the above cytogenetic features.1

Cytogenetic testing was carried out locally.

Methods

Table 1. Patient demographics and baseline characteristics

Belamaf 2.5 mg/kg (N=97) Belamaf 3.4 mg/kg (N=99)

HR

(n=41)

SR

(n=56)

HR

(n=48)

SR

(n=51)

Age, years; median (range) 67.0 (42–85) 62.5 (39–85) 67.5 (49–84) 67.0 (34–81)

Female, n (%)

Male, n (%)

16 (39)

25 (61)

30 (54)

26 (46)

27 (56)

21 (44)

16 (31)

35 (69)

Prior therapies, n;

median (range)6 (3–11) 7 (3–21) 6 (3–21) 6 (3–15)

ISS stage at screening, n (%)

I

II

III

9 (22)

17 (41)

15 (37)

13 (23)

16 (29)

27 (48)

3 (6)

31 (65)

14 (29)

15 (29)

20 (39)

16 (31)

Cytogenetic markers, n (%)*

17p13del

t(4;14)

t(14;16)

1q21+

16 (39)

11 (27)

7 (17)

25 (61)

0

0

0

0

23 (48)

11 (23)

2 (4)

30 (63)

0

0

0

0

Number of cycles; median (range) 3 (1–15) 3 (1–14)† 4 (1–14) 3 (1–9)

*Patients could have more than one HR cytogenetic marker. †Data not available for 2 patients.

References

1. Chng WJ, et al. Leukemia 2014;28:269–77.

2. Sonneveld P, et al. Blood 2016;127:2955–62.

3. Tai YT, et al. Blood 2014;123:128–38.

4. Tai YT, Anderson KC. Immunotherapy 2015;7:1187.

5. Lonial S, et al. Lancet Oncol 2020;21:207–221.

6. Lonial S, et al. ASCO 2020 Poster 436.

7. Sawyer JR, et al. Leukemia 2017;31:637–44.

8. Rajkumar SV, et al. Lancet Oncol 2014;15:e538–48.

9. Kumar S, et al. Lancet Oncol 2016;17:e328–46.

10. Common Terminology Criteria for Adverse Events (CTCAE)

v.4.03. National Cancer Institute 2010

https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-

06-14_QuickReference_8.5x11.pdf [Accessed April 8, 2020].

Disclosures

ADC has received grant funding from GlaxoSmithKline, Bristol-Myers Squibb, and Novartis; personal

fees from Janssen, Takeda, Oncopeptides, Kite Pharma, and Seattle Genetics; and personal fees and

other association with GlaxoSmithKline and Celgene. ST received consulting fees from Celgene, Amgen,

and GlaxoSmithKline; honoraria from Celgene, Janssen, Takeda, Sanofi, Karyopharm, and Amgen

Canada; and research funding from Celgene, Janssen, Amgen, GlaxoSmithKline, and Genentech. SL

has received grant funding and personal fees from Celgene and Takeda, and personal fees from

Novartis, Bristol-Myers Squibb, GlaxoSmithKline, Amgen, Merck, and Janssen. EL received consulting

fees from Adaptive Biotechnologies, Akcea, and Pharmacyclics. HCL has received grant funding and

personal fees from Amgen, Celgene, Janssen, and Takeda; personal fees from GlaxoSmithKline and

Sanofi, and grant funding from Daiichi Sankyo. BB received travel and accommodation expenses and

honoraria from Janssen-Cilag. TF has nothing to disclose. AKN received consulting fees from Amgen,

Janssen Oncology, Celgene, Spectrum Pharmaceuticals, Bristol-Myers Squibb, GlaxoSmithKline,

Takeda, Oncopeptides, and Karyopharm Therapeutics; personal fees from GlaxoSmithKline; and

research funding from Amgen, Janssen Oncology, and Takeda. NC received research funding from

Cellectar. AC received consulting fees from Celgene, Novartis, Amgen, Janssen Oncology, Seattle

Genetics, Bristol-Myers Squibb, Karyopharm Therapeutics, Genzyme, OncoPeptides, Takeda,

Antengene, GlaxoSmithKline, and Secura Bio; and research funding from Celgene, Novartis, Janssen,

Pharmacyclics, Amgen, Seattle Genetics, and Takeda. IG is an employee of and holds stocks/shares in

GlaxoSmithKline and holds stocks/shares in Novartis. SP and JO are employees of and hold stocks and

shares in GlaxoSmithKline. PR has received grant funding and personal fees from Celgene, Takeda, and

Oncopeptides; grant funding from Bristol-Myers Squibb, and personal fees from Janssen, Karyopharm,

Amgen, and Sanofi.

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Acknowledgments

This study was funded by GlaxoSmithKline

(GSK 205678; NCT03525678); drug linker

technology licensed from Seattle Genetics;

monoclonal antibody produced using

POTELLIGENT Technology licensed from BioWa.

Editorial assistance was provided by Martina

Stagno d’Alcontres CMPP, PhD, and Sarah Hauze,

PhD, at Fishawack Indicia Ltd and funded by GSK.

*For questions, please contact the presenting author: adam.cohen@uphs.upenn.edu

Abbreviations

3L: 3 prior lines of therapy

AE: Adverse event

AESI: Adverse events of special interest

AST: Aspartate aminotransferase

BCMA: B-cell maturation antigen

Belamaf: Belantamab mafodotin

CBR: Clinical benefit rate

CI: Confidence interval

CTCAE: Common Terminology Criteria for Adverse

Events

DoR: Duration of response

DREAMM: Driving Excellence in Approaches to

Multiple Myeloma

ECOG: Eastern Cooperative Oncology Group

HR: High risk

IMWG: International Myeloma Working Group

ISS: International Staging System

IV: Intravenous

NR: Not reached

ORR: Overall response rate

OS: Overall survival

PFS: Progression-free survival

PR: Partial response

Q3W: Every 3 weeks

RRMM: Relapsed/refractory multiple myeloma

SAE: Serious adverse event

SR: Standard risk

Patient demographics and baseline characteristics

Patient demographics and baseline characteristics are reported in Table 1.

Median numbers of prior lines of therapy were balanced across groups.

The most frequently recorded cytogenetic risk factors for patients in this study were 17p13del and 1q21+.

Efficacy

The ORRs were comparable in both HR and SR patients; although there were some numerical differences

these were not considered meaningful (Figures 2A, 2B). For 2.5-mg/kg and 3.4-mg/kg groups, respectively:

• HR: 27% (97.5% CI 14.2–42.9) and 40% (97.5% CI 24.1–56.7).

• SR: 34% (97.5% CI 20.4–49.7) and 31% (97.5% CI 17.7–47.9).Figure 1. DREAMM-2 study design5

Key secondary outcomes

• DoR (time from ≥PR until

disease progression [PD] or

death due to PD)

• Other efficacy: CBR, PFS, OS

• Safety, including ocular findingsPatients:

3L+ RRMM

Treatment until disease

progression or

unacceptable toxicity

Belamaf 2.5 mg/kg

IV, Q3W

(n=97)

Belamaf 3.4 mg/kg

IV, Q3W

(n=99)

Primary outcome

ORR:

% of patients with ≥PR

Screening Randomization

1:1*

Table 2. Most frequent AEs (≥25%) and AESIs

Event, n (%)

Belamaf 2.5 mg/kg (N=95) Belamaf 3.4 mg/kg (N=99)

HR (n=41) SR (n=54) HR (n=48) SR (n=51)

Hematologic AEs

Anemia

Thrombocytopenia*

10 (24)

17 (41)

14 (26)

18 (33)

20 (42)

31 (65)

18 (35)

25 (49)

Non-hematologic AEs

AST increased

Fatigue

Nausea

Pyrexia

9 (22)

4 (10)

11 (27)

11 (27)

10 (19)

11 (20)

12 (22)

10 (19)

12 (25)

14 (29)

16 (33)

11 (23)

11 (22)

12 (24)

16 (31)

14 (27)

Ocular AEs

Dry eye†

Keratopathy

Vision blurred‡

5 (12)

24 (59)

8 (20)

8 (15)

43 (80)

14 (26)

10 (21)

38 (79)

20 (42)

14 (27)

36 (71)

12 (24)

SAEs

Related to study treatment

Fatal SAE

Fatal SAE related to study treatment

19 (46)

7 (17)

3 (7)

1 (2)

19 (35)

4 (7)

0

0

24 (50)

6 (13)

2 (4)

0

23 (45)

14 (27)

7 (14)

2 (4)

Duration of response (months)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pro

po

rtio

n a

live

an

d

pro

gre

ssio

n-f

ree

0.0

0.2

0.4

0.6

0.8

1.0 HR cytogeneticsTreatment

2.5 mg/kg

3.4 mg/kg

Number at risk

(Number of events)2.5 mg/kg

3.4 mg/kg

11(0)

19(0)

11(0)

19(0)

9(2)

19(0)

9(2)

15(2)

8(3)

15(2)

6(4)

12(5)

6(4)

10(7)

5(5)

8(9)

5(5)

8(9)

3(5)

6(9)

0(5)

2(9) 0(9)

Duration of response (months)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pro

po

rtio

n a

live

an

d

pro

gre

ssio

n-f

ree

0.0

0.2

0.4

0.6

0.8

1.0Treatment

2.5 mg/kg

3.4 mg/kg

SR cytogenetics

Number at risk

(Number of events)2.5 mg/kg

3.4 mg/kg

19(0)

16(0)

19(0)

16(0)

16(1)

16(0)

13(3)

13(3)

11(3)

13(3)

10(4)

9(7)

9(5)

5(8)

8(5)

4(9)

5(5)

3(9)

2(5)

2(9)

1(5)

1(9)

0(5)

0(9)

10(4)

7(7)

Figure 2A. Profile plot of responders by cytogenic risk: initial dose 2.5 mg/kg

Figure 2B. Profile plot of responders by cytogenic risk: initial dose 3.4 mg/kg

Median DoR was NR for HR (95% CI 1.4–NR) or SR (95% CI 4.2–NR) patients in the

2.5-mg/kg group. In the 3.4-mg/kg group, median DoR was 6.2 months for both HR (95% CI 4.8–NR) and SR

(95% CI 4.2–NR) patients (Figure 3).

The probability of maintaining a response at 9 months for the HR cohort was 52% (95% CI 20%–77%) and 47%

(95% CI 23%–68%); and 68% (95% CI 38%–85%) and 38% (95% CI 13%–62%) in the SR cohort in the

2.5-mg/kg and 3.4-mg/kg groups, respectively.

Median PFS was 2.1 months (95% CI 0.8–3.7) for HR patients and 2.9 months (95% CI 2.0–6.2) for SR patients

in the 2.5-mg/kg group. In the 3.4-mg/kg group, median PFS was 5.8 months (95% CI 1.5–6.9) for HR patients

and 3.1 months (95% CI 1.4–5.6) for SR patients (Figure 4).

The probability of being progression-free and alive at 6 months for the HR cohort was 30% (95% CI 16%–45%)

and 46% (95% CI 31%–60%), and 37% (95% CI 23%–51%) and 32% (95% CI 18%–46%) in the SR cohort, in

the 2.5-mg/kg and 3.4-mg/kg groups, respectively.

Median OS for the HR cohort was estimated to be 9.4 months (95% CI 4.3–13.1) and 13.8 months

(95% CI NR–NR), and 11.9 (95% CI 11.4–NR) and 9.7 months (95% CI 7.4–NR) in the SR cohort, in the 2.5-

mg/kg and 3.4-mg/kg groups, respectively.

Safety

• Overall rates of AEs were similar among all groups (Table 2).

• Changes in the corneal epithelium observed on eye examination (keratopathy/microcyst-like epithelial changes

[MECs]) were the most frequently reported AE in both dose groups, irrespective of cytogenetic status.

• Overall rates of anemia and thrombocytopenia were higher in HR versus SR patients.

• Three fatal treatment-related serious AEs (SAEs) occurred: 1 HR patient (2.5-mg/kg), and 2 SR patients (3.4-mg/kg).

Time from randomization (months)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pro

po

rtio

n a

live

an

d

pro

gre

ssio

n-f

ree

0.0

0.2

0.4

0.6

0.8

1.0Treatment

2.5 mg/kg

3.4 mg/kg

SR cytogenetics

Number at risk

(Number of events)

2.5 mg/kg

3.4 mg/kg

56(0)

51(0)

39(11)

30(16)

33(17)

27(19)

19(27)

21(22)

17(28)

15(27)

15(30)

14(28)

14(30)

12(30)

12(31)

10(32)

12(31)

7(34)

11(32)

4(36)

7(33)

4(36)

3(33)

2(36)

0(33)

1(36) 0(36)

2.5 mg/kg

3.4 mg/kg

41(0)

48(0)

24(15)

32 (11)

21(18)

27(16)

15(23)

24(18)

12(26)

24(18)

12(26)

22(20)

10(27)

19(23)

10(27)

13(28)

8(29)

12(29)

7(29)

12(29)

5(30)

8(30)

1(30)

4(30)

0(30)

1(30) 1(30) 0(31)

0.0

0.2

0.4

0.6

0.8

1.0

Number at risk

(Number of events)

Time from randomization (months)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pro

po

rtio

n a

live

an

d

pro

gre

ssio

n-f

ree

HR cytogeneticsTreatment

2.5 mg/kg

3.4 mg/kg

Figure 4. PFS

Figure 3. DoR

Aim

To further evaluate the efficacy and safety of single-agent belamaf in patients with RRMM and

HR cytogenetic factors in a post-hoc analysis.

*Includes preferred terms thrombocytopenia, platelet count decreased, and cerebral haemorrhage. †Includes preferred terms dry eye, eye pruritus, ocular

discomfort, and foreign body sensation in eyes. ‡Includes preferred terms vision blurred, visual impairment, diplopia, and visual acuity reduced.

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*Patients stratified based on number of previous lines of therapy (≤4 vs >4) and presence or absence of high-risk cytogenetic features.