Contributions
Abstract: PB1453
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
In the ECHELON-2 phase 3 clinical trial, brentuximab vedotin, a CD30-directed antibody-drug conjugate, combined with cyclophosphamide, doxorubicin, and prednisone (A+CHP) showed efficacy in patients (pts) with peripheral T‑cell lymphoma (PTCL) across a range of CD30 expression levels, including the lowest eligible level of 10% by IHC.
It is expected that A+CHP will demonstrate efficacy in PTCL with <10% CD30 expression because: i) clinical responses to brentuximab vedotin occurred in pts with low and undetectable CD30 expression (Jagadeesh 2019); and ii) the activity of CHP chemotherapy in PTCL is unrelated to CD30 expression. This study will include subjects with PTCL subtypes other than systemic anaplastic large cell lymphoma (sALCL).
Aims
To describe the rationale and study design of SGN35-032 (EudraCT 2020-002336-74), a study of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (A+CHP) for patients with previously untreated PTCL with <10% CD30 expression.
Methods
This is a dual-cohort, open-label, multicenter, phase 2 clinical trial (EudraCT 2020-002336-74) designed to evaluate the efficacy and safety of A+CHP in subjects with non-sALCL PTCL and CD30 expression <10% on tumor cells. Up to approximately 40 subjects will be enrolled in each of the CD30 negative (expression <1%) and the CD30 positive (expression ≥1% to <10%) cohorts. Only subjects with CD30 expression <10% per central confirmation will be analyzed for the primary and secondary endpoints. Subjects will receive 21-day cycles of A+CHP for a target of 6-8 cycles.
The primary endpoint of this trial is objective response rate (ORR) per blinded independent central review (BICR) using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Key secondary endpoints include complete remission (CR) and progression-free survival (PFS) per BICR and overall survival.
Key inclusion criteria include adults with newly diagnosed PTCL, excluding sALCL, per the WHO 2016 classification; CD30 expression <10% by local assessment; and FDG-avid disease by PET and measurable disease of at least 1.5 cm by CT, as assessed by the site radiologist.
Lymphoma response and progression will be assessed by BICR per Cheson 2007 and modified Lugano criteria (Cheson 2014). A PET scan is required at baseline, after Cycle 4, and after the completion of study treatment. Follow-up restaging CT scans will be performed over the next two years.
Efficacy and safety endpoints will be summarized with descriptive statistics by cohort, for both the CD30 negative and the CD30 positive cohorts. Time-to-event endpoints, such as PFS, will be estimated using Kaplan-Meier methodology and Kaplan-Meier plots will be presented. Medians for time‑to‑event analyses (eg, median PFS),will be presented and two-sided 95% confidence intervals will be calculated using the log-log transformation method.
The trial currently is open at sites in the US. Sites in Europe are expected to open in early 2021.
Results
N/A
Conclusion
N/A
Keyword(s): Peripheral T-cell lymphoma
Abstract: PB1453
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
In the ECHELON-2 phase 3 clinical trial, brentuximab vedotin, a CD30-directed antibody-drug conjugate, combined with cyclophosphamide, doxorubicin, and prednisone (A+CHP) showed efficacy in patients (pts) with peripheral T‑cell lymphoma (PTCL) across a range of CD30 expression levels, including the lowest eligible level of 10% by IHC.
It is expected that A+CHP will demonstrate efficacy in PTCL with <10% CD30 expression because: i) clinical responses to brentuximab vedotin occurred in pts with low and undetectable CD30 expression (Jagadeesh 2019); and ii) the activity of CHP chemotherapy in PTCL is unrelated to CD30 expression. This study will include subjects with PTCL subtypes other than systemic anaplastic large cell lymphoma (sALCL).
Aims
To describe the rationale and study design of SGN35-032 (EudraCT 2020-002336-74), a study of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (A+CHP) for patients with previously untreated PTCL with <10% CD30 expression.
Methods
This is a dual-cohort, open-label, multicenter, phase 2 clinical trial (EudraCT 2020-002336-74) designed to evaluate the efficacy and safety of A+CHP in subjects with non-sALCL PTCL and CD30 expression <10% on tumor cells. Up to approximately 40 subjects will be enrolled in each of the CD30 negative (expression <1%) and the CD30 positive (expression ≥1% to <10%) cohorts. Only subjects with CD30 expression <10% per central confirmation will be analyzed for the primary and secondary endpoints. Subjects will receive 21-day cycles of A+CHP for a target of 6-8 cycles.
The primary endpoint of this trial is objective response rate (ORR) per blinded independent central review (BICR) using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Key secondary endpoints include complete remission (CR) and progression-free survival (PFS) per BICR and overall survival.
Key inclusion criteria include adults with newly diagnosed PTCL, excluding sALCL, per the WHO 2016 classification; CD30 expression <10% by local assessment; and FDG-avid disease by PET and measurable disease of at least 1.5 cm by CT, as assessed by the site radiologist.
Lymphoma response and progression will be assessed by BICR per Cheson 2007 and modified Lugano criteria (Cheson 2014). A PET scan is required at baseline, after Cycle 4, and after the completion of study treatment. Follow-up restaging CT scans will be performed over the next two years.
Efficacy and safety endpoints will be summarized with descriptive statistics by cohort, for both the CD30 negative and the CD30 positive cohorts. Time-to-event endpoints, such as PFS, will be estimated using Kaplan-Meier methodology and Kaplan-Meier plots will be presented. Medians for time‑to‑event analyses (eg, median PFS),will be presented and two-sided 95% confidence intervals will be calculated using the log-log transformation method.
The trial currently is open at sites in the US. Sites in Europe are expected to open in early 2021.
Results
N/A
Conclusion
N/A
Keyword(s): Peripheral T-cell lymphoma