A PHASE I STUDY IN T CELL LYMPHOMA PATIENTS TREATED WITH ANTI-CD70 SIMPLE ANTIBODY™ ARGX-110
(Abstract release date: 05/19/16)
EHA Library. Michot J. 06/09/16; 132513; E964
Dr. Jean-Marie Michot
Contributions
Contributions
Abstract
Abstract: E964
Type: Eposter Presentation
Background
CD70 is a cell surface marker transiently expressed on activated B, T cells and dendritic cells. The interaction via its receptor CD27 results in survival, proliferation and lymphocyte differentiation. In a large number of solid tumours types, CD70 is overexpressed but without receptor co-expression. As overexpression of CD70 is paralleled by high expression of its receptor CD27 in TCL, the CD70/CD27 axis appears critical for proliferation and survival of malignant cells in T-cell lymphoma.
Aims
ARGX-110 is a novel glycoengineered monoclonal antibody targeting CD70 and blocking CD27 signaling, leading to a direct mode of action lysing CD70+ tumor cells (via CDC, ADCP and enhanced ADCC) and indirect anti-tumor restoring immune surveillance.
Methods
(NCT01813539) A phase I trial was initiated with ARGX-110, dose escalated to investigate safety, clinical pharmacology and determine the RP2D, in refractory or relapsed solid tumors and hematological malignancies on patients with CD70 + tumors (defined by IHC > 10%+). ARGX-110 was given to 65 patients at doses from 0.1 to 10 mg/kg intravenously every 3W.
Results
Preclinical data: Immunohistochemistry on TCL patient samples confirmed overexpression of CD70 (>10% CD70+ tumor cells) in 40/73 PTCL (55%) and 15/21 CTCL (71%) samples. Serum soluble CD27 levels were elevated in TCL patients compared to healthy subjects (670 ± 1096 vs 192 ± 44 IU/ml, respectively, p= 0.0062).Phase 1 heme results: Nine patients received ARGX-110 for a TCL. Histological TCL types were 3 Cutaneous TCL (CTCL) and 6 Peripheral TCL (PTCL). ARGX-110 was well tolerated with no grade >3 adverse events related to the study drug. A clinical and/or biological response was observed in 4/9 of T-cell Lymphoma patients; CTCL (n=3) and PTCL-AITL (n=1) patients. Response consisted in 2 patients with CTCL Sezary syndrome (treated at 0.1 and 10 mg/kg, respectively) in a >90% reduction in the circulating malignant clone, with a clinical partial response in the skin in one patient. The other patient with CTCL TFH lymphoma (treated at 5 mg/kg) achieved a PR. One patient with PTCL with Angioimmunoblastic T-cell Lymphoma (AITL) reached a PR (5 mg/kg dose) and had a resolution of lymphoma associated auto-immune hemolytic anemia.
Conclusion
In the TCL patients treated with ARGX-110, a signal of clinical and/or biological anti-tumor activity was observed. These preliminary results support further investigation of ARGX-110 in TCL.
Session topic: E-poster
Keyword(s): T cell lymphoma
Type: Eposter Presentation
Background
CD70 is a cell surface marker transiently expressed on activated B, T cells and dendritic cells. The interaction via its receptor CD27 results in survival, proliferation and lymphocyte differentiation. In a large number of solid tumours types, CD70 is overexpressed but without receptor co-expression. As overexpression of CD70 is paralleled by high expression of its receptor CD27 in TCL, the CD70/CD27 axis appears critical for proliferation and survival of malignant cells in T-cell lymphoma.
Aims
ARGX-110 is a novel glycoengineered monoclonal antibody targeting CD70 and blocking CD27 signaling, leading to a direct mode of action lysing CD70+ tumor cells (via CDC, ADCP and enhanced ADCC) and indirect anti-tumor restoring immune surveillance.
Methods
(NCT01813539) A phase I trial was initiated with ARGX-110, dose escalated to investigate safety, clinical pharmacology and determine the RP2D, in refractory or relapsed solid tumors and hematological malignancies on patients with CD70 + tumors (defined by IHC > 10%+). ARGX-110 was given to 65 patients at doses from 0.1 to 10 mg/kg intravenously every 3W.
Results
Preclinical data: Immunohistochemistry on TCL patient samples confirmed overexpression of CD70 (>10% CD70+ tumor cells) in 40/73 PTCL (55%) and 15/21 CTCL (71%) samples. Serum soluble CD27 levels were elevated in TCL patients compared to healthy subjects (670 ± 1096 vs 192 ± 44 IU/ml, respectively, p= 0.0062).Phase 1 heme results: Nine patients received ARGX-110 for a TCL. Histological TCL types were 3 Cutaneous TCL (CTCL) and 6 Peripheral TCL (PTCL). ARGX-110 was well tolerated with no grade >3 adverse events related to the study drug. A clinical and/or biological response was observed in 4/9 of T-cell Lymphoma patients; CTCL (n=3) and PTCL-AITL (n=1) patients. Response consisted in 2 patients with CTCL Sezary syndrome (treated at 0.1 and 10 mg/kg, respectively) in a >90% reduction in the circulating malignant clone, with a clinical partial response in the skin in one patient. The other patient with CTCL TFH lymphoma (treated at 5 mg/kg) achieved a PR. One patient with PTCL with Angioimmunoblastic T-cell Lymphoma (AITL) reached a PR (5 mg/kg dose) and had a resolution of lymphoma associated auto-immune hemolytic anemia.
Conclusion
In the TCL patients treated with ARGX-110, a signal of clinical and/or biological anti-tumor activity was observed. These preliminary results support further investigation of ARGX-110 in TCL.
Session topic: E-poster
Keyword(s): T cell lymphoma
Abstract: E964
Type: Eposter Presentation
Background
CD70 is a cell surface marker transiently expressed on activated B, T cells and dendritic cells. The interaction via its receptor CD27 results in survival, proliferation and lymphocyte differentiation. In a large number of solid tumours types, CD70 is overexpressed but without receptor co-expression. As overexpression of CD70 is paralleled by high expression of its receptor CD27 in TCL, the CD70/CD27 axis appears critical for proliferation and survival of malignant cells in T-cell lymphoma.
Aims
ARGX-110 is a novel glycoengineered monoclonal antibody targeting CD70 and blocking CD27 signaling, leading to a direct mode of action lysing CD70+ tumor cells (via CDC, ADCP and enhanced ADCC) and indirect anti-tumor restoring immune surveillance.
Methods
(NCT01813539) A phase I trial was initiated with ARGX-110, dose escalated to investigate safety, clinical pharmacology and determine the RP2D, in refractory or relapsed solid tumors and hematological malignancies on patients with CD70 + tumors (defined by IHC > 10%+). ARGX-110 was given to 65 patients at doses from 0.1 to 10 mg/kg intravenously every 3W.
Results
Preclinical data: Immunohistochemistry on TCL patient samples confirmed overexpression of CD70 (>10% CD70+ tumor cells) in 40/73 PTCL (55%) and 15/21 CTCL (71%) samples. Serum soluble CD27 levels were elevated in TCL patients compared to healthy subjects (670 ± 1096 vs 192 ± 44 IU/ml, respectively, p= 0.0062).Phase 1 heme results: Nine patients received ARGX-110 for a TCL. Histological TCL types were 3 Cutaneous TCL (CTCL) and 6 Peripheral TCL (PTCL). ARGX-110 was well tolerated with no grade >3 adverse events related to the study drug. A clinical and/or biological response was observed in 4/9 of T-cell Lymphoma patients; CTCL (n=3) and PTCL-AITL (n=1) patients. Response consisted in 2 patients with CTCL Sezary syndrome (treated at 0.1 and 10 mg/kg, respectively) in a >90% reduction in the circulating malignant clone, with a clinical partial response in the skin in one patient. The other patient with CTCL TFH lymphoma (treated at 5 mg/kg) achieved a PR. One patient with PTCL with Angioimmunoblastic T-cell Lymphoma (AITL) reached a PR (5 mg/kg dose) and had a resolution of lymphoma associated auto-immune hemolytic anemia.
Conclusion
In the TCL patients treated with ARGX-110, a signal of clinical and/or biological anti-tumor activity was observed. These preliminary results support further investigation of ARGX-110 in TCL.
Session topic: E-poster
Keyword(s): T cell lymphoma
Type: Eposter Presentation
Background
CD70 is a cell surface marker transiently expressed on activated B, T cells and dendritic cells. The interaction via its receptor CD27 results in survival, proliferation and lymphocyte differentiation. In a large number of solid tumours types, CD70 is overexpressed but without receptor co-expression. As overexpression of CD70 is paralleled by high expression of its receptor CD27 in TCL, the CD70/CD27 axis appears critical for proliferation and survival of malignant cells in T-cell lymphoma.
Aims
ARGX-110 is a novel glycoengineered monoclonal antibody targeting CD70 and blocking CD27 signaling, leading to a direct mode of action lysing CD70+ tumor cells (via CDC, ADCP and enhanced ADCC) and indirect anti-tumor restoring immune surveillance.
Methods
(NCT01813539) A phase I trial was initiated with ARGX-110, dose escalated to investigate safety, clinical pharmacology and determine the RP2D, in refractory or relapsed solid tumors and hematological malignancies on patients with CD70 + tumors (defined by IHC > 10%+). ARGX-110 was given to 65 patients at doses from 0.1 to 10 mg/kg intravenously every 3W.
Results
Preclinical data: Immunohistochemistry on TCL patient samples confirmed overexpression of CD70 (>10% CD70+ tumor cells) in 40/73 PTCL (55%) and 15/21 CTCL (71%) samples. Serum soluble CD27 levels were elevated in TCL patients compared to healthy subjects (670 ± 1096 vs 192 ± 44 IU/ml, respectively, p= 0.0062).Phase 1 heme results: Nine patients received ARGX-110 for a TCL. Histological TCL types were 3 Cutaneous TCL (CTCL) and 6 Peripheral TCL (PTCL). ARGX-110 was well tolerated with no grade >3 adverse events related to the study drug. A clinical and/or biological response was observed in 4/9 of T-cell Lymphoma patients; CTCL (n=3) and PTCL-AITL (n=1) patients. Response consisted in 2 patients with CTCL Sezary syndrome (treated at 0.1 and 10 mg/kg, respectively) in a >90% reduction in the circulating malignant clone, with a clinical partial response in the skin in one patient. The other patient with CTCL TFH lymphoma (treated at 5 mg/kg) achieved a PR. One patient with PTCL with Angioimmunoblastic T-cell Lymphoma (AITL) reached a PR (5 mg/kg dose) and had a resolution of lymphoma associated auto-immune hemolytic anemia.
Conclusion
In the TCL patients treated with ARGX-110, a signal of clinical and/or biological anti-tumor activity was observed. These preliminary results support further investigation of ARGX-110 in TCL.
Session topic: E-poster
Keyword(s): T cell lymphoma
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