Clinical and Biological Evaluation of the Novel CD30/CD16A ...
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0 10 20 30 40 50 60 70 0 5 28 56 77 154 CD4 + CD 275+ cells Days % CD69 expressing NK cells over time in non- responders CU002 CU004 CU005 CU006 0 10 20 30 40 50 60 70 0 5 28 56 77 CD69 % cells Days % CD69 expressing NK cells over time in responders CU001 CU003 CU007 Pre Study Cycle 1 Week 11 Post Cycle 2 Clinical and Biological Evaluation of the Novel CD30/CD16A Tetravalent Bispecific Antibody (AFM13) in Relapsed or Refractory CD30-Positive Lymphoma with Cutaneous Presentation: A Biomarker Phase Ib/IIa Study (NCT03192202). • Population: subjects with relapsed or refractory CD30 expressing lymphoma with cutaneous involvement • AFM13 is a CD30/CD16A targeting high affinity bispecific tetravalent antibody that engages and activates NK cells and macrophages. • AFM13 was well tolerated. • AFM13 demonstrated a high ORR of 50% and showed activity post-brentuximab vedotin failure. • Tumor biopsies in patients who were responding to AFM13 showed increased NK cells both before and during treatment. • A phase II multicenter international study of AFM13 in PTCL and T-MF is planned. COI : AFFIMED provided research support for this study . Ahmed Sawas, MD 1 , Pei-Hsuan Chen 2 , George Vlad, PhD 1 , Mikel Lipschitz 2 , Jennifer Lue, MD 1 , Changchun Deng, MD, PhD 1 , Jennifer E Amengual, MD 1 , Enrica Marchi, MD 1 , Francesca Montanari, MD 1 , Maher Abdul-Hay, MD 4 , Jonah Shulman, MD 5 , Hager Elgedawe 1 , Matthew Shong 1 , Karen Khan, RN 1 , Larisa Geskin, MD 1 , Scott J. Rodig, MD, Ph 2,3 , and Owen A. O'Connor, MD, PhD 1 1 Columbia University Medical Center, New York, NY; 2 Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA. 3 Brigham & Women's Hospital, Boston, Massachusetts; Boston, MA. 4 New York University Perlmutter Cancer Center, New York, NY. 5 Mount Sini School of Medicine, New York, NY METHODS BACKGROUND RESULTS CONCLUSION • Response assessment performed by mSWAT, photography, PET imaging and peripheral blood flow cytometry. • A second cycle was administered if there was no progression of disease. • Skin biopsies, whole blood and plasma were collected: pretreatment, day 5 post first dose, week 4 and week 8 of therapy. • Tumor biopsies were analyzed and evaluated by a pathologist and IHC image analyzer to characterize immune cell subpopulations. • Peripheral blood samples were analyzed by flow cytometry. Cohort Dose regimen Total exposure Dose Schedule Duration Cohort 1 1.5 mg/kg weekly weeks 1-8 12 mg/kg Cohort 2 7.0 mg/kg weekly weeks 1-8 56 mg/kg Cohort 3 7.0 mg/kg CIVI * weekly weeks 1-8 56 mg/kg Cohort 4 200mg flat dose weekly weeks 1-8 1600 mg 15- ICML - IMMUNOTHERAPY - No. 259 Rapid and Durable Response in T-MF Response in a T- MF subject then consolidated with an Allogenic stem cell transplant. Responses were seen in: • Nodes • Skin • Peripheral blood • Increased CD69 expression (activation marker) on circulating NK cells from responders vs. non- responders. • Decreased in circulating NK cells during therapy with post therapy recovery, by following cells CD56+ CD3- , CD56+ CD16+ and NKp46+. • Circulating CD4+ CD25+ T cells (Tregs) decrease in responders vs. non-responders. *1 mg/kg loading 6mg/kg as continuous infusion for 5 days per week Cohort Disease Toxicity Response 1 S-ALCL, Alk (-) No AE PR T-MF No AE POD C- ALCL Rash (G4) Skin infection (G3) CR 2 MF IRR (G1) SD T-MF IRR (G1) SD T-MF Skin infection (G3) IRR (G1) Not assessed 3 T-MF No AE PR S-ALCL, Alk (-) No AE PR MF No AE POD 4 T-MF No AE PR ∆ +98% ∆ -31% RESULTS Patient Demographics Table N= 10 Median age, (range) 65 (37-79) Male (%) 7 (70%) Race (% white/ non-white) 30%/70% Median number of prior therapy, (range) 4 (1-11) Patients progressed on brentuximab vedotin 2 Total Skin Electron Beam Radiotherapy 5 Disease Histologies Transformed Mycosis Fungoides (T-MF) 5 Mycosis Fungoides, non-transformed (MF) 2 Systemic Anaplastic Large Cell Lymphoma- ALK negative (S- ALCL, ALK -) 2 Cutaneous Anaplastic Large Cell Lymphoma (C-ALCL) 1 Skin Response in T-MF Patient Peripheral Blood Biomarker Correlatives • Tumor biopsies showed increased infiltration of CD56+ NK cells pre therapy and during therapy in responders (red) vs. non-responders (blue). • NK cell (green) cytotoxicity through the expression of Granzyme B (red) was seen in responders vs. non-responders by comparing pre therapy tumor biopsy (top panel) to W4 tumor biopsy (bottom panel). • No change in CD68 expressing cells (not shown). CD56% CD30% • Tumor CD30 expressing cells decrease significantly in response to therapy in responders (red) vs. non- responders (blue). Pre Post Tumor Biopsies Biomarker Correlatives
Transcript of Clinical and Biological Evaluation of the Novel CD30/CD16A ...
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Pre Study Cycle 1 Week 11 Post Cycle 2
Clinical and Biological Evaluation of the Novel CD30/CD16A Tetravalent Bispecific
Antibody (AFM13) in Relapsed or Refractory CD30-Positive Lymphoma with
Cutaneous Presentation: A Biomarker Phase Ib/IIa Study (NCT03192202).
• Population: subjects with relapsed or refractory
CD30 expressing lymphoma with cutaneous
involvement
• AFM13 is a CD30/CD16A targeting high affinity
bispecific tetravalent antibody that engages and
activates NK cells and macrophages.
• AFM13 was well tolerated.
• AFM13 demonstrated a high ORR of 50% and
showed activity post-brentuximab vedotin failure.
• Tumor biopsies in patients who were responding to
AFM13 showed increased NK cells both before and
during treatment.
• A phase II multicenter international study of AFM13
in PTCL and T-MF is planned.
COI : AFFIMED provided research support for this study .
Ahmed Sawas, MD1, Pei-Hsuan Chen2, George Vlad, PhD1, Mikel Lipschitz2, Jennifer Lue, MD1, Changchun Deng, MD, PhD1, Jennifer E Amengual, MD1, Enrica Marchi, MD1, Francesca
Montanari, MD1, Maher Abdul-Hay, MD4, Jonah Shulman, MD5, Hager Elgedawe1, Matthew Shong1, Karen Khan, RN1, Larisa Geskin, MD1, Scott J. Rodig, MD, Ph2,3, and
Owen A. O'Connor, MD, PhD1
1Columbia University Medical Center, New York, NY; 2Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA. 3Brigham & Women's Hospital, Boston, Massachusetts; Boston, MA.4New York University Perlmutter Cancer Center, New York, NY. 5Mount Sini School of Medicine, New York, NY
METHODS
BACKGROUND RESULTS
CONCLUSION
• Response assessment performed by mSWAT,
photography, PET imaging and peripheral blood flow
cytometry.
• A second cycle was administered if there was no
progression of disease.
• Skin biopsies, whole blood and plasma were
collected: pretreatment, day 5 post first dose, week 4
and week 8 of therapy.
• Tumor biopsies were analyzed and evaluated by a
pathologist and IHC image analyzer to characterize
immune cell subpopulations.
• Peripheral blood samples were analyzed by flow
cytometry.
CohortDose regimen Total
exposureDose Schedule Duration
Cohort 1 1.5 mg/kg weekly weeks 1-8 12 mg/kg
Cohort 2 7.0 mg/kg weekly weeks 1-8 56 mg/kg
Cohort 37.0 mg/kg
CIVI * weekly weeks 1-8 56 mg/kg
Cohort 4200mg
flat doseweekly weeks 1-8 1600 mg
15- ICML - IMMUNOTHERAPY - No. 259
Rapid and Durable Response in T-MF
Response in a T-
MF subject then
consolidated with
an Allogenic stem
cell transplant.
Responses were
seen in:• Nodes
• Skin
• Peripheral blood
• Increased CD69 expression (activation marker)
on circulating NK cells from responders vs. non-
responders.
• Decreased in circulating NK cells during therapy
with post therapy recovery, by following cells
CD56+ CD3- , CD56+ CD16+ and NKp46+.
• Circulating CD4+ CD25+ T cells (Tregs) decrease
in responders vs. non-responders.
*1 mg/kg loading 6mg/kg as continuous infusion for 5 days per week
Cohort Disease Toxicity Response
1
S-ALCL, Alk (-) No AE PR
T-MF No AE POD
C- ALCLRash (G4)
Skin infection (G3)CR
2
MF IRR (G1) SD
T-MF IRR (G1) SD
T-MFSkin infection (G3)
IRR (G1)
Not
assessed
3
T-MF No AE PR
S-ALCL, Alk (-) No AE PR
MF No AE POD
4 T-MF No AE PR
∆ +98% ∆ -31%
RESULTS
Patient Demographics Table N= 10
Median age, (range) 65 (37-79)
Male (%) 7 (70%)
Race (% white/ non-white) 30%/70%
Median number of prior therapy, (range) 4 (1-11)
Patients progressed on brentuximab vedotin 2
Total Skin Electron Beam Radiotherapy 5
Disease Histologies
Transformed Mycosis Fungoides (T-MF) 5
Mycosis Fungoides, non-transformed (MF) 2
Systemic Anaplastic Large Cell Lymphoma-
ALK negative (S- ALCL, ALK -)2
Cutaneous Anaplastic Large Cell Lymphoma
(C-ALCL)1
Skin Response in T-MF Patient
Peripheral Blood Biomarker Correlatives
• Tumor biopsies showed increased infiltration of
CD56+ NK cells pre therapy and during therapy in
responders (red) vs. non-responders (blue).
• NK cell (green) cytotoxicity through the expression
of Granzyme B (red) was seen in responders vs.
non-responders by comparing pre therapy tumor
biopsy (top panel) to W4 tumor biopsy (bottom
panel).
• No change in CD68 expressing cells (not shown).
CD56%
CD30%
• Tumor CD30 expressing cells decrease significantly
in response to therapy in responders (red) vs. non-
responders (blue).
Pre
Post
Tumor Biopsies Biomarker Correlatives
