1. No category

High Relapse Rate after Allo
1
Relapsed Hodgkin’s Lymphoma
•  Up to half of patients with relapsed HL progress
again after autologous transplant and others aren’t
able to undergo autograft
•  Regimens for relapsed disease have short remission
durations and most rely on combination
chemotherapy:
–  ICE
–  GVD
–  IGeV
–  ChlVPP
–  GDP
•  Anti-CD30 antibodies alone (SGN-30) not beneficial.
SGN-35/Brentuximab vedotin
•  Antibody-drug conjugate
–  CD30 monoclonal antibody
–  Monomethyl
auristatin E
2
Phase I Study of SGN-35
•  4 center trial for patients with CD30+
malignancies
•  45 patients treated (42 w/ HL)
•  MTD of 1.8mg/kg every 3 weeks
•  DLT’s:
–  Neutropenia/sepsis leading to death (n=1) [3.6mg/kg]
–  Grade 3 renal failure (n=1) [2.7mg/kg]
–  Grade 3 hyperglycemia (n=1) [2.7mg/kg]
–  Grade 3 prostatitis/febrile neutropenia (n=1) [2.7mg/kg]
–  Grade 4 thrombocytopenia (n=1) [1.8mg/kg]
Younes et al, NEJM 2010
Phase I Study of SGN-35
•  Responses at MTD (1.8mg/kg; N=12):
•  CR-4
•  PR-2
•  SD-5
•  PD-1
•  Common adverse events:
–  Neuropathy (36%)
–  Grade 3 or 4 neutropenia (16%)
–  Grade 3 or 4 thrombocytopenia (9%)
Younes et al, NEJM 2010
3
Phase 2 Study-Eligible Patients
•  HL relapsed after autologous transplant
•  Documented CD30+ disease w/
measurable disease
•  ECOG 0-1
•  ANC >1000
•  Plts > 50,000
•  No prior allogeneic transplant
4
Phase 2 Study Design
•  Open label study at 25 centers in US,
Canada, Europe
•  Accrual: Feb-Aug 2009
•  SGN-35 1.8mg/kg q3 wks up to 16 doses
•  CT’s and PET/CT’s scheduled at regular
intervals (i.e., after cycles 2, 4, 7, 10….)
•  Reviewed in an Independent Radiology
Review Facility (IRF)
Phase 2 Statistical Plan
•  Primary endpoint: Overall Response Rate
•  Secondary endpoints:
–  CR Rate
–  Progression-free survival
–  Overall survival
–  Incidence and severity of adverse events
•  100 planned patients allowed a response rate of
29% to exclude a rate ≤ 20% with 95%
confidence.
•  Pre-planned intra-patient PFS comparison
5
Results- Patient Characteristics
•  N = 102 ( 48 males, 54 females)
•  All had prior autologous transplant
•  Median 3.5 prior chemotherapy regimens
(Range 1-13)
•  71% had primary refractory disease
•  42% refractory to prior therapy
•  Median 6.7 months from transplant to first
post-transplant relapse
Results-Efficacy
Median time to response:
5.7 weeks (Range 5.1 to 56
weeks)
Median time to CR:
12 weeks (Range: 5.1 to 56
weeks)
Subgroup analyses showed
no group who did not achieve
anti-tumor activity.
6
Results-Efficacy
Intrapatient PFS Comparison
•  Median PFS most prior therapy:
–  4.1 months
•  Median PFS w/ SGN-35:
–  7.8 months
7
Results-Safety
•  Median no of cycles: 10 (Range 1-16)
•  Most common adverse events:
–  Neuropathy (42%)
–  Nausea (35%)
–  Fatigue (34%)
–  Neutropenia (19%)
–  Diarrhea (18%)
–  Fever (14%)
Results-Adverse Events
8
Discussion
•  Promising, highly active, well-tolerated
outpatient therapy.
•  But….
Discussion
•  Allogeneic transplant still only chance for cure
and has been successfully undertaken after
SGN-35.
•  Recently concluded study evaluating SGN-35 in
post-transplant maintenance.
•  Long-term benefit may be in combination and
not as mono-therapy in relapsed setting, or
possibly utilized in the up-front setting.
9
Discussion
•  Brentuximab + ABVD or AVD HL
–  Multicenter phase I study
–  96% ORR
–  95% CR in ABVD; 92% CR in AVD
–  44% of patients in ABVD arm discontinued
bleomycin due to pulmonary toxicity
–  24% of patients in ABVD had Grade 3 or 4
pulmonary toxicity
Ansell et al, ASH 2012
10