1. ASSIST-FL: Rituximab Biosimilar GP2013 vs Rituximab in Treatment-Naive Patients With Advanced Follicular Lymphoma
New Findings in Hematology: Independent Conference Coverage of ASH 2016*; December 3-6, 2016; San Diego, California
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This activity is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, and Seattle Genetics.

2. ASSIST-FL: Background
Follicular lymphoma: most common indolent lymphoma, representing approximately 20% of NHL diagnoses[1,2]
Rituximab: chimeric IgG1 mAb approved for pts with NHL, chronic lymphocytic leukemia, RA, and other conditions[3]
GP2013: biosimilar to rituximab[3]
Biosimilars developed to have no clinically meaningful differences (safety, purity, potency) vs originator drug
PK/PD similar to rituximab in pts with RA[4]
Current ASSIST-FL study compares efficacy, safety, and PK/PD of GP2013 vs rituximab addition to cyclophosphamide, vincristine, and prednisone in treatment-naive pts with advanced follicular lymphoma[5]
NHL, non-Hodgkin lymphoma; PD, pharmacodynamics; PK, pharmacokinetics; RA, rheumatoid arthritis.
1. The Non-Hodgkin’s Lymphoma Classification Project. Blood. 1997;89: National Cancer Institute PDQ. Adult non-Hodgkin lymphoma treatment. 3. Visser J, et al. BioDrugs. 2013;27: Smolen J, et al. EULAR Abstract FRI Jurczak W, et al. ASH Abstract 1809.
Slide credit: clinicaloptions.com

3. ASSIST-FL: Phase III Study Design
Multicenter, international, randomized, double-blind, active-controlled, parallel-group phase III trial
Primary endpoint: ORR equivalence (entire 90% CI for ORR difference within 12% margin)
Secondary endpoints: response, PFS, OS, PK/PD, safety
Stratified by FLIPI score risk group (low/intermediate vs high) and geographic region
Combination Phase
Maintenance Phase*
2 yrs
GP mg/m2 for 8 cycles
Cyclophosphamide 750 mg/m2 IV on Day 1 Vincristine 1.4 mg/m2 IV on Day 1
Prednisone 100 mg PO on Days 1-5 (n = 314)
GP2013 maintenance Q3M
(n = 231)
Treatment-naive pts with advanced stage follicular lymphoma
(N = 629)
Rituximab 375 mg/m2 for 8 cycles
Cyclophosphamide 750 mg/m2 IV on Day 1 Vincristine 1.4 mg/m2 IV on Day 1
Prednisone 100 mg PO on Days 1-5 (n = 315)
Rituximab maintenance Q3M
(n = 231)
CVP, cyclophosphamide, vincristine, prednisone; FLIPI, Follicular Lymphoma International Prognostic Index; PD, pharmacodynamics; PK, pharmacokinetics.
*For responding pts.
Slide credit: clinicaloptions.com
Jurczak W, et al. ASH Abstract 1809.

4. ASSIST-FL: Baseline Pt Characteristics
GP2013-CVP (n = 312)
R-CVP (n = 315)
Full Analysis Set Population* (n = 627)
Mean age, yrs (SD)
< 60 yrs, n (%)
≥ 60 yrs, n (%)
57.4 (11.86)
163 (52.2)
149 (47.8)
56.4 (11.72)
175 (55.6)
140 (44.4)
56.9 (11.79)
338 (53.9)
289 (46.1)
Female sex, n (%)
181 (58.0)
169 (53.7)
350 (55.8)
Mean BMI (SD)
26.4 (4.89)
26.0 (4.82)
26.2 (4.86)
ECOG PS, n (%) 1 2
No data
179 (57.4)
125 (40.1)
5 (1.6)
3 (1.0)
123 (39.0)
13 (4.1)
4 (1.3)
354 (56.5)
248 (39.6)
18 (2.9)
7 (1.1)
Mean time from diagnosis to randomization, mos (SD)
3.9 (11.95)
3.3 (6.73)
3.6 (9.69)
BMI, body mass index; CVP, cyclophosphamide, vincristine, prednisone; ECOG, Eastern Cooperative Oncology Group; PS, performance status; R-CVP, rituximab, cyclophosphamide, vincristine, prednisone; SD, standard deviation.
*Includes all randomized pts who received ≥ 1 partial/complete study dose.
Slide credit: clinicaloptions.com
Jurczak W, et al. ASH Abstract 1809.

5. ASSIST-FL: Baseline Disease Characteristics
GP2013-CVP (n = 312)
R-CVP (n = 315)
Full Analysis Set Population* (n = 627)
Ann Arbor Staging System Status, n (%)
III IV
143 (45.8)
169 (54.2)
135 (42.9)
180 (57.1)
278 (44.3)
349 (55.7)
FLIPI risk group, n (%)
Low (0-1 factors)
Intermediate (2 factors)
High (≥ 3 factors)
30 (9.6)
106 (34.0)
176 (56.4)
35 (11.1)
103 (32.7)
177 (56.2)
65 (10.4)
209 (33.3)
353 (56.3)
CVP, cyclophosphamide, vincristine, prednisone; FLIPI, Follicular Lymphoma International Prognostic Index; R-CVP, rituximab, cyclophosphamide, vincristine, prednisone.
*Includes all randomized pts who received ≥ 1 partial/complete study dose.
Slide credit: clinicaloptions.com
Jurczak W, et al. ASH Abstract 1809.

6. ASSIST-FL: Overall Response and Survival
In per protocol set population during maintenance phase, ORR difference for GP2013 vs rituximab was -0.40% (90% CI: -5.10% to 4.30%) by blinded central review
Similar best ORR between arms during combination phase
Sensitivity analysis found no significant effect of data missing in 5.6% of pts
Median PFS and OS both NR at data cutoff (July 10, 2015)
Overall Response, %
GP2013-CVP
R-CVP
ORR
87.1
87.5 CR
14.8
13.4 PR
72.3
74.1
CVP, cyclophosphamide, vincristine, prednisone; NR, not reached; R-CVP, rituximab, cyclophosphamide, vincristine, prednisone.
Slide credit: clinicaloptions.com
Jurczak W, et al. ASH Abstract 1809.

7. ASSIST-FL: Pharmacokinetics and Pharmacodynamics
Comparable PK/PD profiles for GP2013 vs rituximab
Cmax geometric mean ratio: 1.00 (90% CI: )
PD comparable when assessed by peripheral CD19+ B-cell count; geometric mean ratio of AUEC[0-21 d]: (90% CI: )
Sampling Time Point
PK Parameter
GP2013-CVP (n = 119)
R-CVP (n = 120)
All Pts (N = 239)
Day 1 in Cycle 4
Mean Cmax, mcg/mL (SD, n)
356.03
(121.61, 108)
350.99
(116.79, 120)
353.48
(118.94, 219)
Mean Ctrough, mcg/mL (SD, n)
66.42
(47.59, 104)
82.13
(61.52, 110)
74.50
(55.62, 214)
Cycle 4
Mean AUC[0-21 d], mcg*day/mL (SD, n)
3320
(872, 20)
3500
(1020, 17)
3400
(933, 37)
Geometric mean AUC[0-21 d], mcg*day/mL
3210
3340
3260
Mean AUCAll, mcg*day/mL (SD, n)
2820
(1250, 24)
2950
(1510, 22)
2880
(1370, 46)
Geometric mean AUCAll, mcg*day/mL
2510
2310
2420
AUEC, area under effect-time curve; AUC, area under curve; CVP, cyclophosphamide, vincristine, prednisone; PD, pharmcodynamic; PK, pharmacokinetics; R-CVP, rituximab, cyclophosphamide, vincristine, prednisone; SD, standard deviation.
Jurczak W, et al. ASH Abstract 1809.

8. ASSIST-FL: Safety
Most frequent serious AE was febrile neutropenia (GP2013: 4.8%; rituximab: 2.9%)
Most frequent cause of death until data cutoff was NHL (2.6% vs 1.9%, respectively)
Outcome, %
GP2013-CVP
R-CVP
AEs
Serious AEs
92.6
22.8
91.4
20.0
AE-related discontinuations
7.4
7.0
Deaths
Combination phase
Until data cutoff (July 10, 2015)
1.3
5.8
2.2
5.4
Antidrug antibodies
Neutralizing antidrug antibodies
1.9
0.7
1.1
AE, adverse event; CVP, cyclophosphamide, vincristine, prednisone; NHL, non-Hodgkin lymphoma; R-CVP, rituximab, cyclophosphamide, vincristine, prednisone.
Slide credit: clinicaloptions.com
Jurczak W, et al. ASH Abstract 1809.

9. ASSIST-FL: AEs During Combination Phase
Study Drug-Related AEs in ≥ 5% of Pts, n (%)
GP2013-CVP (n = 312)
R-CVP (n = 315)
All Grades
Grade 3/4
Neutropenia
65 (20.8)
44 (14.1)
76 (24.1)
51 (16.2)
Constipation
3 (1.0)
32 (10.2)
1 (0.3)
Infusion-related reaction
41 (13.1)
37 (11.7)
2 (0.6)
Nausea
34 (10.9)
35 (11.1)
Peripheral neuropathy
33 (10.6)
4 (1.3)
25 (7.9)
Fatigue
26 (8.3)
18 (5.7)
Paresthesia
23 (7.4)
30 (9.5)
Asthenia
21 (6.7)
22 (7.0)
Leukopenia
7 (2.2)
24 (7.6)
13 (4.1)
Alopecia
20 (6.4)
17 (5.4)
16 (5.1)
15 (4.8)
Vomiting
14 (4.4)
Pyrexia
11 (3.5)
AE, adverse event; CVP, cyclophosphamide, vincristine, prednisone; R-CVP, rituximab, cyclophosphamide, vincristine, prednisone.
Jurczak W, et al. ASH Abstract 1809.

10. ASSIST-FL: Conclusions
Difference in ORR between GP2013-CVP vs R-CVP was within prespecified 12% margin for equivalence (-0.40%; 90% CI: -5.10% to 4.30%)
CR and PR rates similar between arms
PK/PD profiles superimposable between arms
Safety profiles and AE rates comparable (any-grade AEs: 92.6% for GP2013-CVP vs 91.4% for R-CVP)
Investigators concluded that GP2013 demonstrated therapeutic equivalence for primary and secondary endpoints as well as a similar safety profile in treatment-naive pts with advanced follicular lymphoma
AE, adverse event; CVP, cyclophosphamide, vincristine, prednisone; PD, pharmacodynamics; PK, pharmacokinetics; R-CVP, rituximab, cyclophosphamide, vincristine, prednisone.
Slide credit: clinicaloptions.com
Jurczak W, et al. ASH Abstract 1809.

11. Go Online for More CCO Coverage of ASH 2016!
Short slideset summaries of all the key data
Additional CME-certified analyses with expert faculty commentary on all the key studies in:
Leukemias
Lymphomas/CLL
Myeloma/plasma cell disorders
MDS and myeloproliferative neoplasms
clinicaloptions.com/oncology