Presented at the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO); June 1–5, 2018; Chicago, IL, USA.

A Phase 2, Multicenter, Open-Label Study of the Safety and Ef� cacy of Luspatercept in Subjects With Myeloproliferative Neoplasm (MPN)-Associated Myelo� brosis and Anemia With or Without RBC Transfusion Dependence

BACKGROUND BACKGROUND BACKGROUND

• Myeloproliferative neoplasm (MPN)-associated myelo� brosis (MF) is a clonal myeloid neoplasm characterized by bone marrow � brosis, defective bone marrow function, extramedullary hematopoiesis, a propensity for transformation to blast phase, and in� ammation1

• Anemia is an important complication of MPN-associated MF, eventually developing in all patients2,3

• Anemia and red blood cell (RBC) transfusion dependence (TD) are independent adverse prognostic and predictive variables for survival among these patients3,4

Luspatercept

• Luspatercept is a recombinant fusion protein consisting of a modi� ed activin receptor type IIB linked to the Fc domain of human immunoglobulin G1 (IgG1) (Figure 1)5,6

• Luspatercept acts as an erythroid maturation agent by binding speci� c transforming growth factor-β (TGF-β) superfamily ligands such as growth differentiation factor-11 (GDF11), blocking their inhibitory effect, and leading to increased RBC production6

• In a recent phase 2 study, luspatercept was shown to be effective and well tolerated for the treatment of anemia in patients with lower-risk myelodysplastic syndromes7

Post-Treatment Follow-Up Period• After treatment discontinuation, follow-up safety data will be collected up to

42 days after the last dose of study treatment• Safety data will then be collected every 3 months for up to 3 years after the last

dose of study treatment or until death, consent withdrawal, or loss to follow-up

Endpoints

• Primary and secondary endpoints are listed in the Table• Exploratory endpoints include treatment exposure–response, biomarkers,

and mutational analyses• All ef� cacy analyses will be performed primarily on the intent-to-treat

population, de� ned as all patients enrolled• Con� rmatory ef� cacy analyses will be performed on the ef� cacy-evaluable

population, de� ned as all patients who: – Received ≥ 3 cycles of study treatment and remain on study for

≥ 21 days after the third study dose OR – Achieved Hb > 13 g/dL in < 3 cycles

• Safety analyses will be performed on all patients receiving ≥ 1 study treatment dose

– Adverse events and laboratory abnormalities are classi� ed according to the NCI-CTCAE version 4.03

• Pharmacokinetic analyses will be based on all patients who have evaluable concentration data to determine the pharmacokinetic parameters

Statistical Analyses• Descriptive statistical analyses will primarily be used• The Kaplan–Meier method may be used to estimate duration of anemia

response• No inferential comparisons between the cohorts will be performed

Study Status

• Enrollment began in November 2017• Target enrollment is 70 patients with MPN-associated MF and anemia, with

or without RBC-TD• As of April 9, 2018 across 24 clinical sites (Figure 3), 12 patients have been

enrolled into the study• Enrollment is currently ongoing (ClinicalTrials.gov identi� er NCT03194542)• If you have a patient who could bene� t from participation in this trial, please

contact the Associate Director of Clinical Trial Disclosure (+1-888-260-1599 or clinicaltrialdisclosure@celgene.com)

REFERENCES REFERENCES REFERENCES1. Mesa RA, et al. Leuk Res. 2011;35(1):12-13.2. Cervantes F, et al. Blood. 2009;113(13):2895-2901.3. Passamonti F, et al. Blood. 2010;115(9):1703-1708.4. Elena C, et al. Haematologica. 2011;96(1):167-170.

5. Attie KM, et al. Am J Hematol. 2014;89(7):766-770.6. Suragani RN, et al. Nat Med. 2014;20(4):408-414.7. Platzbecker U, et al. Lancet Oncol. 2017;18(10):1338-1347.

ACKNOWLEDGEMENTS ACKNOWLEDGEMENTS ACKNOWLEDGEMENTS ANDANDAND DISCLOSURES DISCLOSURES DISCLOSURESThis study was sponsored by Celgene Corporation, Summit, NJ, USA. The authors received editorial assistance and printing support in the preparation of this poster from Excerpta Medica (Daniel Gilmartin, PhD), supported by Celgene Corporation. The authors are fully responsible for all content and editorial decisions.

R.A.M.: Celgene Corporation, CTI, Genentech, Gilead Sciences, Incyte, NS Pharma, P� zer, PharmaEssentia, Promedior – research funding; AOP Orphan Pharmaceuticals, Incyte, Novartis – travel/accommodations/expenses; AOP Orphan Pharmaceuticals, Novartis, Shire – honoraria; Baxalta, Galena Biopharma, Incyte, Novartis – consulting or advisory role. G.B.: no con� icts of interest to disclose. C.N.H.: Celgene Corporation, Novartis – research funding; Celgene Corporation, Gilead Sciences, Novartis – honoraria; Novartis – speakers bureau. J.J.K.: AOP Orphan Pharmaceuticals, Novartis – research funding; Incyte, Novartis, Shire – travel/accommodations/expenses; Novartis, Shire – honoraria; Incyte, Novartis, Shire – consulting or advisory role. R.P.G., T.G., J.P.: Celgene Corporation – employment, stock and other ownership interests, travel/accommodations/expenses. A.L.: Celgene Corporation – employment, stock and other ownership interests, honoraria. P.G.L.: Acceleron Pharma – employment; Abbott Laboratories, AbbVie, Acceleron Pharma, FibroGen – stock and other ownership interests. M.L.S.: Acceleron Pharma – employment, patents/royalties/other intellectual property; Acceleron Pharma, Pulmatrix – leadership, stock and other ownership interests. S.V.: Gilead Sciences, Incyte, Novartis – honoraria; Incyte, Novartis – consulting or advisory role; AstraZeneca, BioPharma Corp., Blueprint Medicines Corp., Bristol-Myers Squibb, Celgene Corporation, CTI, Galena BioPharma, Genentech, Gilead Sciences, Incyte, Lilly Oncology, NS Pharma, P� zer, Promedior, Roche, Seattle Genetics – research funding.

CORRESPONDENCE CORRESPONDENCE CORRESPONDENCERuben A. Mesa – mesar@uthscsa.edu

POSTER TPS7083

Ruben A. Mesa1, Giovanni Barosi2, Claire N. Harrison3, Jean-Jacques Kiladjian4, Robert Peter Gale5, Abderrahmane Laadem5, Torsten Gerike5, Peter G. Linde6, Matthew L. Sherman6, Joseph Pariseau5, Srdan Verstovsek7

1UT Health San Antonio Cancer Center, San Antonio, TX, USA; 2IRCCS Policlinico San Matteo, Pavia, Italy; 3Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 4Hôpital Saint-Louis and Université Paris Diderot, Paris, France; 5Celgene Corporation, Summit, NJ, USA; 6Acceleron Pharma, Cambridge, MA, USA; 7MD Anderson Cancer Center, Houston, TX, USA

STUDY DETAILS ( STUDY DETAILS ( STUDY DETAILS (contcontcont.).).)

Table. Study Endpoints

Endpoints Cohorts 1 and 3a (Anemia Only) Cohorts 2 and 3b (RBC-TD)

Primary ≥ 1.5 g/dL Hb increase from baseline over any consecutive 84-day period without an RBC transfusion

RBC-TI over any consecutive 84-day period

Secondary • Time to anemia response• Duration of anemia response• Symptom response improvement

(defi ned as ≥ 50% reduction in fatigue symptoms or ≥ 50% reduction in total symptom score by MF-SAF or MPN-SAF)

• HRQoL improvement• Safety• Pharmacokinetics• Antidrug antibodies

• Time to anemia response• Duration of anemia response• Frequency of RBC transfusions

(mean RBC units/4 weeks)• Frequency of RBC-TD (defi ned as

reduction in transfusion burden by ≥ 50% from baseline over any consecutive 84-day period)

• Symptom response improvement (defi ned as ≥ 50% reduction in fatigue symptoms or ≥ 50% reduction in total symptom score by MF-SAF or MPN-SAF)

• HRQoL improvement• Safety• Pharmacokinetics• Antidrug antibodies

Hb, hemoglobin; HRQoL, health-related quality of life; MF-SAF, Myelofi brosis Symptom Assessment Form; MPN-SAF, Myeloproliferative Neoplasm Symptom Assessment Form; RBC, red blood cell; TD, transfusion dependence; TI, transfusion independence.

ScreeningPost-treatment

follow-upperiod

Cohort 1(Anemia only)

0 RBC units/84 daysup to cycle 1, day 1

(n = 20)

Cohort 3(Patients on

ruxolitinib as part of standard ofcare therapy)

Anemia only (3a) and RBC-TD (3b)

(n = 30)

Cohort 2(RBC-TD)

Mean 2–4 RBCunits/28 days

(n = 20)

If clinicalbenefit

Continue forup to an

additional1.5 years

If no clinicalbenefit

Discontinuetreatment

Day 169disease

responseassessment

Primary Phase168 days

Post-TreatmentFollow-Up

Period3 years post

last dose

Par

alle

l Enr

ollin

g

End

of

Stu

dy

Treatment PeriodPrimary Phase

168 days

Screening Period

4 weeks

Figure 2. Study Design

RBC, red blood cell; TD, transfusion dependence.

B

A

Figure 3. Clinical Sites in USA (A) and Europe (B)

Erythropoietin-dependent

Luspatercept-responsive

BFU-E CFU-E Pro-E Baso-E Poly-E Ortho-E Reticulocyte RBCs

Hemoglobin

Figure 1. Mechanism of Action of Luspatercept

Baso-E, basophilic erythroblast; BFU-E, burst-forming unit–erythroid; CFU-E, colony-forming unit–erythroid; Ortho-E, orthochromatic erythroblast; Poly-E, polychromatophilic erythroblast; Pro-E, proerythroblast; RBC, red blood cell.

OBJECTIVE OBJECTIVE OBJECTIVE

• To evaluate the ef� cacy and safety of luspatercept for the treatment of anemia in patients with MPN-associated MF with or without RBC-TD

STUDY DETAILS STUDY DETAILS STUDY DETAILS

• This is an ongoing, multicenter, open-label, phase 2 study

Study Population

• Inclusion criteria: – Age ≥ 18 years – MPN-associated MF (primary MF, post-polycythemia vera MF,

or post-essential thrombocythemia MF) – Anemia, de� ned as:

Cohorts 1 and 3a: ≥ 3 hemoglobin (Hb) levels ≤ 9.5 g/dL on ≥ 3 days (including day of dosing), with no RBC transfusions in the 84 days prior to cycle 1 day 1 (C1D1); ≥ 42 days between measurements will be excluded

Cohorts 2 and 3b: average RBC transfusion frequency of 2–4 RBC units/28 days over ≥ 84 days prior to C1D1, with no interval > 42 days without ≥ 1 RBC transfusion; Hb < 13 g/dL on C1D1 prior to luspatercept administration

– Eastern Cooperative Oncology Group performance status ≤ 2

Study Design and Treatment

• The study comprises 3 periods (Figure 2): – Screening period – Treatment period (primary phase, disease response assessment at

day 169, and extension phase) – Post-treatment follow-up period

Screening Period• All screening procedures are conducted ≤ 28 days prior to enrollment

Treatment Period• All patients will receive luspatercept 1 mg/kg subcutaneously on day 1

of each 21-day cycle• Patients will be enrolled in cohorts according to RBC transfusion requirement:

– Cohorts 1 and 3a (anemia only) – Cohorts 2 and 3b (RBC-TD)

• Best supportive care may be used in combination with study treatment• Disease response assessment should be completed at day 169 following

the � rst dose of study treatment – Responders may continue treatment for up to an additional 1.5 years – Non-responders will discontinue treatment

STUDY DETAILS (STUDY DETAILS (STUDY DETAILS (contcontcont.).).)

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Trial Registry: NCT03194542