14ICML Poster presented at: Printing supported by:

Presented at the International Conference on Malignant Lymphoma | Lugano, Switzerland | 14–17 June 2017

BACKGROUND

METHODS

OBJECTIVES

RESULTS

• Pola + BR or BG has an acceptable safety profile in pts with R/R FL or DLBCL

• Pola + BR or BG showed promising efficacy including some durable responses

• Enrollment has been completed in Phase II randomization portions comparing Pola + BR vs BR in R/R FL and R/R DLBCL. Results from these arms of the study will be presented when data are available

CONCLUSIONS

Figure 1: Pola Mode of Action

Figure 3: Adverse Events (>20% patients)

ACKNOWLEDGEMENTSScientific support was provided by Grace Ku, MD, of Genentech, Inc. Editorial assistance for this poster was provided by Anne Nunn, PhD, of Envision Pharma Group and funded by F. Hoffmann-La Roche. Thank you to all participating patients, investigators, and research staff. This study was sponsored by F. Hoffmann-La Roche Ltd.

MJM: grants and personal fees from Genentech; AH: grants and personal fees from BMS, Genentech, Merck, Pharmacyclics, and grants from Seattle Genetics; MK: personal fees from Seattle Genetics; AM: grants from Genentech, BMS, Incyte, MedImmune, Merck, Pharmacyclics, Seattle Genetics; SA: personal fees from Janssen, Lundbeck, Shire. IF: personal fees from Amgen, Gilead, Janssen, Lundbeck, Merck, Novartis, Roche, Seattle Genetics; TMK: nothing to disclose; WSK: grants from Celgene, Dong-A, J&J, Kyowa-Kirin, Novartis, Takeda, and personal fees from Celltrion; FB: grants and personal fees from F. Hoffmann-La Roche; JR: grants and personal fees from Takeda, personal fees from Novartis and Seattle Genetics; CF: grants from Abbvie, Acerta, Celgene, Gilead Sciences, Infinity Pharmaceuticals, Janssen Pharmaceuticals, Millennium/Takeda, Onyx Pharmaceuticals, Pharmacyclics, NIH, Spectrum, and personal fees from Bayer, Celgene, Gilead, Optum Rx, Seattle Genetics, Spectrum; LB and W-JH are employees of Genentech, Inc; LS: grants from Roche/Genentech, personal fees from Abbvie, Amgen, Celgene, Gilead, Janssen, Lundbeck, Pfizer, Seattle Genetics, TG Therapeutics.

Polatuzumab Vedotin plus Bendamustine and Rituximab or Obinutuzumab in Relapsed/Refractory Follicular Lymphoma or Diffuse

Large B-Cell Lymphoma: Updated Results of a Phase IB/II StudyMatthew Matasar,1 Alex F. Herrera, 2* Manali Kamdar,3* Amitkumar Mehta,4 Sarit Assouline,5 Isabelle Fleury,6 Tae Min Kim,7 Won Seog Kim,8

Francesc Bosch,9 John Radford,10 Christopher R. Flowers,11 Lilian Bu,12 Wan-Jen Hong,13 Laurie H. Sehn14

1Memorial Sloan Kettering Cancer Center, New York, NY, US; 2City of Hope, Duarte, CA, US; 3University of Colorado, Denver, Department of Medicine, Denver, CO, US; 4University of Birmingham, Birmingham, AL, US; 5Jewish General Hospital, Montreal, Canada; 6Department of Hematology, Maisonneuve-Rosemont Hospital and University of Montreal, Montreal, Canada; 7Seoul National University Hospital, Seoul, South Korea; 8Samsung Medical Center, Seoul, South Korea; 9Hospital Universitari Vall

d’Hebron, Barcelona, Spain; 10University of Manchester and the Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 11Winship Cancer Institute of Emory University, Atlanta, GA, US; 12Roche, Shanghai, China; 13Genentech, Inc., South San Francisco, CA, US; 14BC Cancer Agency, Vancouver, Canada; *Presenting author

Poster: 284

Primary• Phase Ib

– Safety and tolerability of Pola + BR or BG– Identify the recommended Phase II dose (RP2D) of Pola when given in

combination with BR or BG

Key Secondary• To evaluate the efficacy of the combination of Pola + BG as measured by:

– Best objective response, objective response at end of treatment (tx), and complete response (CR) at end of tx by investigator or independent review committee (IRC) (IRC data not yet available)

• As of 28 February 2017, 24 pts (12 FL, 12 DLBCL) were enrolled in the safety run-in and 20 R/R FL and 21 R/R DLBCL pts were enrolled into the expansion cohort. Safety run-in confirmed the Pola RP2D to be 1.8 mg/kg

• Baseline characteristics are shown in Table 1. In the DLBCL expansion cohort, 1 pt was enrolled but did not receive study tx, and is included in efficacy assessments

• Patients (pts) with transplant-ineligible relapsed/refractory (R/R) follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) have poor outcomes

• Polatuzumab vedotin (Pola) is an antibody-drug conjugate (ADC) designed for the targeted delivery of the potent microtubule inhibitor monomethyl auristatin E (MMAE) to cells expressing CD79b (Figure 1)

• Pola combined with rituximab (R) has previously demonstrated promising response rates in pts with R/R FL or DLBCL. The addition of bendamustine (B) to Pola-R and substitution of obinutuzumab (G) for R could improve outcomes in these pts

• We report updated results from the safety run-in of a Phase Ib/II study evaluating Pola combined with BR or BG in R/R DLBCL or R/R FL, and the expansion cohort evaluating Pola combined with BG in R/R DLBCL or R/R FL (Figure 2; Clinical Trials.gov NCT02257567)

Key Inclusion Criteria• Relapsed or refractory FL (Grade 1, 2, or 3a) or DLBCL• At least 1 bi-dimensionally measurable lesion defined as >1.5 cm in long axis• Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2 • For pts with prior bendamustine, response duration must be >1 year

Key Exclusion Criteria• Prior allogeneic stem cell transplant• Autologous transplant <100 days from C1D1• Eligible for autologous stem cell transplant• History of transformation of low-grade lymphoma to DLBCL• Current Grade >1 peripheral neuropathy (PN)

Table 1: Baseline Characteristics

CharacteristicsFL DLBCL

Pola + BR(n=6)

Pola + BG(n=26)

Pola + BR(n=6)

Pola + BG(n=26)

Median age, yr (range) 68 (54–73) 62 (37–86) 65 (58–79) 67 (30–86)

Male, n (%) 2 (33) 14 (54) 4 (67) 15 (58)

Baseline ECOG PS, n (%)0–12

6 (100)0

26 (100)4 (15)

6 (100)0

22 (85)4 (15)

IPI/FLIPI1 at entry, n (%)0–123–5

04 (67)2 (33)

3 (12)11 (42)12 (46)

1 (17)3 (50)2 (33)

3 (12)4 (15)

19 (73)

Stage III/IV disease, n (%) 6 (100) 22 (85) 4 (67) 22 (85)

Bulky disease, n (%)a 2 (33) 4 (15) 1 (17) 6 (23)

Extranodal disease, n (%) 4 (67) 12 (46) 4 (67) 19 (73)

Refractory to last tx, n (%)b 3 (50) 11 (48) 5 (83) 22 (85)aBulky disease ≥7.5 cm; bRefractory=no response or progression within 6 months of last dose of tx.FLIPI1, Follicular Lymphoma International Prognostic Index; IPI, International Prognostic Index

Therapy Delivered• Details of therapy delivered are shown in Table 2. The only adverse events (AE)

leading to Pola discontinuation in >1 pt were PN (2 pts) and infection (2 pts). Cytopenias were the most common AEs leading to Pola dose reduction/delay

Table 2: Therapy DeliveredFL DLBCL

Pola + BR(n=6)

Pola + BG(n=26)

Pola + BR (n=6)

Pola + BG(n=26)

Completed 6 cycles, n (%) 4 (67) 19 (73) 3 (50) 10 (39)

Median cycles received, n (range) 6 (3–6) 6 (1–6) 5 (2–6) 4 (1–6)

Median duration of follow-up, mo (range)

18.7 (17.6–21.7)

10.2(1.4–17.3)

20(1.5–25.2)

9.3(1.4–18.6)

Pola discontinuation for AE, n (%) 0 4 (15) 1 (17)a 5 (19)

Pola dose reduction, n (%) 0 2 (8) 0 0

Median cycle to first reduction, n (range)

NA 4 (3–5) NA NA

Pola dose delay, n (%) 2 (33) 15 (58) 3 (50) 12 (46)

Median cycle to first delay, n (range) 4 (2–5) 5 (2–6) 4 (3–5) 3 (2–6)aFever due to progressive disease; Duration of follow-up: C1D1 to last date known to be alive or date of death. NA, not applicable

Safety • Among the 64 pts enrolled in the FL and DLBCL cohorts who received at least one

dose of study tx, the AEs occurring in >20% of pts with either FL or DLBCL are shown in Figure 3

• Table 3 shows Grade 3/4 AEs occurring in >10% of pts. The most common non-hematological Grade 3/4 AEs were infection and fatigue

• Infections were the only serious AE occurring in >10% of pts: 22% in FL and 31% in DLBCL. Half occurred during study tx

• Grade 5 AEs occurred in 7 (11%) pts with 4 occurring during study tx. These included pneumonia, progressive multifocal leukoencephalopathy during C1, “general physical health deterioration,” and acute pulmonary edema in a pt with previously unknown history of severe aortic stenosis

• PN incidence is shown in Table 4. Overall PN occurred in 33% of pts with most being Grade 1. Grade ≥2 occurred in 13% of pts. PN led to Pola discontinuation in 2 pts and reduction/delay in 3 pts

Table 3: Grade 3/4 Adverse Events (>10% patients)FL

(n=32)DLBCL(n=32)

Total(N=64)

Hematological, n (%)NeutropeniaThrombocytopeniaAnemiaFebrile neutropenia

10 (30)4 (13)2 (6)2 (6)

9 (28)5 (16)4 (13)4 (13)

19 (30)9 (14)6 (9)6 (9)

Non-Hematological, n (%)Infectiona

Fatigue5 (16)2 (6)

7 (22)4 (13)

13 (20)6 (9)

aGrade 3/4 infection, defined by SOC infection and infestation; data are for BR and BG groups combined. SOC, MeDRA System Organ Class

Table 4: Peripheral NeuropathyFL

(n=32)DLBCL(n=32)

History of prior PN, n (%) 5 (16) 16 (50)

Ongoing PN at study entry, n (%) 4 (13) 13 (41)

All grades, n (%) Grade ≥2

11 (34)3 (9)

10 (31)4 (13)

Action taken with Pola, n (%)ReducedDelayedDiscontinued

2 (6)10

00

2 (6)

Data are for BR and BG groups combined

Efficacy • Responses by positron emission tomography/computed tomography (PET/CT) are

reported in Table 5 and duration of responses are shown in Figure 4

Table 5: Investigator-Assessed Response by PET/CTa

FL DLBCL

Pola + BR(n=6)

Pola + BG(n=26)

Pola + BR (n=6)

Pola + BG(n=27)

Best Objective Response

ORR, n (%)CRPRSDPDUE

6 (100)4 (67)2 (33)

000

23 (89)17 (65)6 (23)

01 (4)2 (8)

3 (50)2 (33)1 (17)

02(33)1 (17)

16 (60)11 (41)5 (19)2 (7)

6 (22)3 (11)

Objective Response at End of Tx

ORR, n (%)CRPR

5 (83)4 (67)1 (17)

21 (81)17 (65)4 (15)

3 (50)2 (33)1 (17)

10 (37)9 (33)1 (4)

Median duration of response, mo (range)b

16.1 (3.8–16.3)

NR (15.2–20.6)

NR (0.03–14.5)

NR (0.03–15.7)

Median PFS, mo (range)b

18.4 (7.2–18.9)

NR(1.4–17.1)

NR (1.5–22.7)

5.4 (0.03–17.6)

aModified Lugano 2014 response criteria: for CR, repeat bone marrow biopsy required to confirm clearance of bone marrow if involved at screening. bKaplan-Meier method; range data are at clinical data cut-off. NR, not reached; ORR, objective response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; UE, unable to evaluate.

Anti-CD79bTargets to B-Cell

malignancies

Linker

MMAEMicrotubule

disrupter

Patients with FL (N=32) Patients with DLBCL (N=32)

DISCLOSURES

Pola 1.8 mg/kg + BR

(n=6/histology)

Pola 1.8 mg/kg + BG

(n=6/histology)

Phase II Expansion: Pola + BG

BR (n=40/histology)

• R/R FL• R/R DLBCL

Pola 1.8 mg/kg + BG (n=20/histology)

• R/R FL (N=80)• R/R DLBCL (N=80)

Phase II Randomization: Pola 1.8 mg/kg + BR vs BR

Pola + BR (n=40/histology)

Safety Run-In Phase: Pola + BR or Pola + BG • R/R FL

• R/R DLBCL

Reported here:

Ongoing:

Tx: Pola 1.8 mg/kg IV with BR or BG every 28 days for FL pts and every 21 days for DLBCL pts for a total of 6 cycles. Response assessed after 3 cycles, end of tx, and every 6 months during follow-up

Figure 2: Study Design

0 20 40 60

Grade 1Grade 2Grade 3Grade 4Grade 5

0204060

Nausea

Fatigue

Diarrhea

PN

Constipation

Rash

Vomiting

Neutropenia

Pyrexia

Decreased appetite

Hypokalemia

Thrombocytopenia

Cough

Pneumonia

0

Figure 4: Time to PFS Events in FL Pts (A) and DLBCL Pts (B)

EXP, expansion cohort.

A

B

Patie

nts

(N=3

2)Pa

tient

s (N

=33)

Day of study

Day of study

0 100 200 300 400 500 600

FL Pola 1.8 mg/kg + BR

EXP FL Pola 1.8 mg/kg + BG

FL Pola 1.8 mg/kg + BG

Continued response

Event (PD or death)

0 100 200 300 400 500 600 700 800

DLBCL Pola 1.8 mg/kg + BR

EXP DLBCL Pola 1.8 mg/kg + BG

DLBCL Pola 1.8 mg/kg + BG

Continued response

Event (PD or death)

Patient not treated

Data are for BR and BG groups combined

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Patients (%)

284--PMatthew Matasar DOI: 10.3252/pso.eu.14ICML.2017

New drug development