100

50

-50

-100

0

Best

% C

hang

e in

Tar

get N

odal

Les

ions

Patients

100

50

-50

-100

0

Best

% C

hang

e in

Tar

get N

odal

Les

ions

Patients

Overall Response Rate (Investigator Assessment per modified IWCLL/IWG Criteria)

CI= confidence interval; CR= complete response; CRi = CR with incomplete marrow recovery; LNRR = lymph node response rate (i.e. >50% decrease in target nodal lesion); ORR= overall response rate; PR= partial response; PRwL = PR with lymphocytosis

• For patients with 17p deletion treated with duvelisib (n=20), the ORR was 80% (95% CI: 63, 98), which included 2 (10%) CRi, 13 (65%) PR, and 1 (5%) PRwL

Progression-Free Survival Per Investigator Assessment

Growth &survival ofmalignant

B cells

Recruitment ofmalignant B cells

Recruitment & differentiation of cellssupporting B cell growth & survival

Tumor-associatedmyeloid cell

PI3K-γ

PI3K-γ

Tumor Microenvironment (TME)

BCR

Cytokinereceptor

Cytokines

Cytokines

Migration, activation, andM2 polarization signals

Cytokinereceptor

CD40R CD40L

Anti-tumorimmune response

CXCL13

CXCR5 CXCR4

CXCL12

CXCR4

CXCL12

CD4+ T cell

PI3K-δ PI3K-γ

Malignant B cell

PI3K-δPI3K-γ

Category N = 89

Median Age (years) 68

Min, Max 39, 90

≥ 65 years, % 61

Sex, %

Male 63

Female 37

Race, %

White 92

Other 5

Unknown 3

Background

The Efficacy of Duvelisib Monotherapy Following Disease Progression on Ofatumumab Monotherapy in Patients with Relapsed/Refractory CLL or SLL in the DUOTM Crossover Extension Study

Bryone Kuss1; Matthew S. Davids2; Peter Hillmen3; Carol Moreno4; James H. Essell5; Nicole Lamanna6; Zsolt Nagy7; Ulrich Jaeger8; Constantine Tam9; Stephan Stilgenbauer10; Paolo Ghia11; Julio Delgado12; Diep Le13; Brenda Jeglinksi13; Marco Montillo14

1Flinders Medical Centre, Bedford Park, AUS; 2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; 3St. James’s Institute of Oncology, The Leeds Teaching Hospitals, Leeds, UK; 4Hospital de la Santa Creu i Sant Pau, Barcelona,Spain; 5Oncology Hematology Care, SCRI, Cincinnati, Ohio, USA; 6New York Presbyterian, Columbia University Medical Center, New York, NY; 71st Department of Internal Medicine, Semmelweis University, Budapest, HUN; 8Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, AUT; 9Peter MacCallum Cancer Centre, St Vincent’s Hospital and University of Melbourne , Melbourne, AUS; 10Department III of Internal Medicine, University Hospital Ulm, Ulm, GER; 11Università Vita-Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele, Milan, ITA;

12Hospital Clinic, Barcelona, SPA; Flinders Medical Centre (FMC), Bedford Park, AUS; 13Verastem Oncology, Needham, MA; 14Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, ITA

Demographics and Baseline Characteristics

• Duvelisib is an oral dual inhibitor of PI3K-δ and PI3K-γ being developed for treatment of hematologic malignancies, including relapsed/refractory (R/R) CLL/SLL

• The Phase 3 DUOTM Study (NCT02004522; Study IPI-145-07) in patients with R/R CLL/SLL met its primary endpoint, with duvelisib monotherapy demonstrating a statistically significant improvement in PFS vs ofatumumab monotherapy (Flinn ASH 2017)

• In DUO, the most common ≥ Gr 3 AEs were hematologic and included neutropenia (30%), anemia (13%), and thrombocytopenia (8%); the most common severe non-hematologic AEs were diarrhea (15%), pneumonia (14%), and colitis (12%)

CategoryDuvelisib monotherapy

N=160Ofatumumab monotherapy

N=159

Median PFS (months) 13.3 * 9.9

95% CI 12.1, 16.8 9.2, 11.3

ORR, % 74 * 45

95% CI 66.9, 80.6 37.5, 53.0

LNRR, % 85 * 16

95% CI 79.5, 90.5 10.1, 21.4

DUO™ Study

Study IPI-145-12

Crossover Study

Ofatumumab IVAdministration same as DUON=8

Duvelisib25 mg BID continuouslyN=89

Duvelisib25 mg BID PO continuously N=160

Ofatumumab IV- 300 mg IV infusion on Day 1- 2000 mg IV weekly (x7) then monthly (x4)N=159

Relapsed or Refractory

CLL/SLL patients

319 Patients Randomized 1:1

Category N = 89

Diagnosis, %

CLL 99

SLL 1

High-Risk Cytogenetics, %

17p deletion present (per central lab) 20

Years from Initial Diagnosis

Median 7

Min, Max 0.5, 22.0

Current Stage – Rai, (n=38), %

I 16

II 34

III 13

IV 37

Current Stage – Binet, (n=51), %

A 0

B 74

C 26

Baseline Lymphocytes (×109/L)

Median 13.96

Min, Max 0.0, 273.2

Prior Treatment N = 89

Median number of prior anticancer therapies

3

Min, Max 2-8

Received ≥ 3 prior lines of therapy, % 61

Prior Therapies, %

Purine Analog 73

Alkylator 96

Cyclophosphamide 72

Bendamustine 38

Chlorambucil 29

Monoclonal antibody 100

Ofatumumab 100

Rituximab 87

Obinutuzumab 2

Alemtuzumab 1

Baseline Characteristics Disease History Prior to DUO Entry

Prior Anticancer Therapy

Efficacy

DUO Study Pre-crossoverOfatumumab

N=89%

Study IPI-145-12 Post-crossoverDuvelisib

N=89%

ORR 28 73

95% CI 19, 37 64, 82

CR 1 0

CRi 0 5

PR 27 57

PRwL 0 11

LNRR 27 73

Percent Change in Nodal Target Lesions (Ofatumumab Pre-crossover)

Percent Change in Nodal Target Lesions (Duvelisib Post-crossover)

Safety

Preferred TermAll Grades

%Grade 3

%Grade 4

%

Hematologic Neutropenia 25 12 10

Nonhematologic Diarrhoea 38 17 0

Pyrexia 23 3 0

Rash 21 5 0

Colitis 11 9 0

Vomiting 11 0 0

Asthenia 11 0 0

Cough 11 0 0

Decreased appetite 10 0 0

Nausea 10 0 0

Pneumonia 10 9 0

0 10 20 30 40 50 60 70 80 90 100

Infection SOC

Neutropenia

Diarrhea

Colitis

Skin reaction SOC

Pneumonia

Transaminitis

Pneumonitis

% of Patients

Adverse Events of Interest

Treatment-Emergent AEs by Grade (>10% Overall) All Causalities

Note: AEs coded using MedDRA version 16.1. Percentages are based on the number of treated patients.

Abbreviation: SOC = system, organ, class

• Few discontinuations due to AEs of interest• Three patients with severe opportunistic infections - Pneumocystis jirovecii pneumonia (PJP) (n=2): 1 not receiving prophylaxis at the

time of onset - Pneumonia cytomegaloviral (n=1) • 1 AE on study leading to death assessed as related to duvelisib: PJP (noted above)

• In this extension study, duvelisib monotherapy achieved robust responses in 89 R/R CLL/SLL patients who had disease progression following ofatumumab treatment on the DUO study

- ORR: 73% on duvelisib (28% on prior ofatumumab)

- Median PFS: 15 months on duvelisib (9 months on prior ofatumumab)

- 83% of evaluable patients had >50% reduction in target nodal lesions

• The safety profile of duvelisib monotherapy was manageable and consistent with what was observed in the Phase 3 DUO study

• These data further support the potential clinical benefit of duvelisib monotherapy in patients with R/R CLL/SLL

Conclusions

Presented at the 2018 American Society for Clinical Oncology Annual Meeting • Chicago, Illinois, USA • June 1-5, 2018

Patient Enrollment and Disposition

Poster # 170; Abstract 7533

Study Enrollment by Region/Country

• 89 of 101 patients treated with ofatumumab with confirmed disease progression on DUO elected to enroll in Study IPI-145-12

• As of 19 July 2017, 60 (67%) patients have discontinued duvelisib, 32 (36%) due to AEs, 16 (18%) due to PD, 4 (5%) due to death, and 8 (9%) for other reasons (e.g. voluntary withdrawal)

• 29 (33%) patients remain on duvelisib

17%11%

12%

13%8%

9%

6%

8%

5%

3%

9%

US (n=7; 8%)Australia (n=5; 6%)New Zealand (n=4; 5%)

Hungary (n=15; 17%) Italy (n=12; 13%) Spain (n=11; 12%)France (n=10; 11%)

Belgium (n=8; 9%) UK (n=8; 9%)Austria (n=7; 8%)Germany (n=2; 3%)

28% (24/87 evaluable patients) had a >50% reduction in target nodal lesions

83% (65/78 evaluable patients) had a >50% reduction in target nodal lesions

100

Prob

abili

ty o

f Pro

gres

sion

-Fre

e Su

rviv

al

89 65 55 42 25 20 10 5 2 1 089 82 63 54 31 13 4 3 2 1 0

Time (months)Number at Risk

80

60

40

20

0 3 6 9 12 15 18 21 24 27 300

Ofatumumab (N= 89) DUO Study Pre-crossoverDuvelisib (N= 89) Study IPI-145-12 Post-crossoverTreatment

≥ Grade 3 AEsAEs leading to discontinuation (any Grade)

Median PFS (months) (95% CI)Ofatumumab (Pre-crossover): 9 (9, 11)Duvelisib (Post-crossover): 15 (10, 17)

Key Efficacy Results from the DUOTM Study (Flinn ASH 2017)

All results per blinded independent review committee*statistically significant vs ofatumumab: p<0.0001LNRR = lymph node response rate (i.e. >50% decrease in target nodal lesion)

• Study IPI-145-12 (NCT02049515) is an open-label, optional, crossover extension study where patients with radiologically confirmed disease progression on DUO were given the option to receive the opposite treatment

• Herein we present data for the 89 patients who voluntarily crossed over following radiologically confirmed disease progression on ofatumumab on DUO and received duvelisib on Study IPI-145-12

• To further characterize duvelisib, an ad-hoc analysis was performed for ORR and PFS for the 89 patients while receiving ofatumumab pre-crossover in the DUO study

• Eligible patients enrolled within 3 months of radiologically-confirmed disease progression on the DUO study (excluding Richter’s transformation or prolymphocytic leukemia)

• Duvelisib 25 mg BID was administered until PD, intolerance, death, or study withdrawal • All patients received mandatory prophylaxis for PJP

Study Design

For more information+1-781-292-4200MedicalAffairs@verastem.com

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