Ignite Creation Date:
2024-05-06 @ 2:42 PM
Last Modification Date:
2024-10-26 @ 1:36 PM
Study NCT ID:
NCT04407741
Status:
RECRUITING
Last Update Posted:
2023-12-12
First Post:
2020-05-20
Brief Title:
Phase ⅠⅡ Study of SHR2554 in Combination With SHR1701 in Patients With Advanced Solid Tumors and B-cell Lymphomas
Sponsor:
Chinese PLA General Hospital
Organization:
Chinese PLA General Hospital
Study Overview
Official Title:
An Open-Label Phase ⅠⅡ Study of EZH2 Inhibitor SHR2554 in Combination With Anti-PD-L1TGFβ Antibody SHR1701 in Patients With Advanced or Metastatic Solid Tumors and RelapsedRefractory B-cell Lymphomas
Status:
RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The potency of immune checkpoint blockade is limited in most solid malignancies one possible reason for which is tumor microenvironment Enhancer of zeste homolog 2 EZH2 as a epigenetic target for cancer therapy has attracted significant interest The combination of EZH2 inhibitors and programmed death-1 ligands transforming growth factor-β PD-L1TGFβ blockade may enhance the efficiency of immunotherapyThe primary objective of this study in phase Ⅰstage is to assess the safety feasibility of EZH2 inhibitor SHR2554 in combination with anti-PD-L1TGFβ antibody SHR1701 in advanced pretreated solid tumors and b-cell lymphomas The phase Ⅱ stage of this study is to primarily evaluate the efficacy of SHR2554 plus SHR1701 and the epigenetic modulating effect of SHR2554
Detailed Description:
Immune checkpoint blockade has led to great strides in the management of various cancers however durable response could be seen in approximately 20 of treated patients with most solid malignancies Immunosuppressive entities such as transforming growth factor-β TGF-β in the tumor microenvironment TME remain a major impediment Enhancer of zeste homolog 2 EZH2 is the core component of the polycomb group complex which play a major role in cellular proliferation and differentiation EZH2 aberration has been seen in a wide range of solid tumors and hematological malignancies affecting tumor progression and immune cells in the tumor microenvironment and it is associated with poor clinical prognosis and outcomes EZH2 is not only an activator of gene expression through different pathways but also a critical epigenetic repressor through histone methylation Therefore EZH2 has attracted significant interest as a potential epigenetic target for cancer treatment It is hypothesized that the combination of EZH2 inhibitors and programmed death-1 ligands transforming growth factor-β PD-L1TGFβ blockade could enhance the efficiency of immunotherapy
The primary objective of this study in phase Ⅰstage is to assess the safety feasibility of EZH2 inhibitor SHR2554 in combination with anti-PD-L1TGFβ antibody SHR1701 in advanced pretreated solid tumors and b-cell lymphomas The second objectives include characterizing the pharmacokinetics of SHR2554 in combination with SHR1701 evaluating the preliminary efficacy of SHR2554 plus SHR1701 and the epigenetic modulating effect of SHR2554 in its combination with anti-PD-L1TGFβ antibody The exploratory objectives are to evaluate the pathological immunological or clinical predictive factors for efficacy and toxicity Based on the data of safety efficacy and recommended dose level obtained from phase Ⅰtrial this study moves into phase Ⅱ stage in which enrolled subjects are randomized to SHR2554 plus SHR 1701 or SHR1701 monotherapy to primarily evaluate the efficacy of SHR2554 plus SHR1701 and the epigenetic modulating effect of SHR2554 The second objectives include evaluating safety and other efficacy parameters such as overall response rate ORR disease control rate DCR duration of response DOR and overall survival OS The exploratory objectives are to evaluate laboratory predicting biomarkers
The primary objective of this study in phase Ⅰstage is to assess the safety feasibility of EZH2 inhibitor SHR2554 in combination with anti-PD-L1TGFβ antibody SHR1701 in advanced pretreated solid tumors and b-cell lymphomas The second objectives include characterizing the pharmacokinetics of SHR2554 in combination with SHR1701 evaluating the preliminary efficacy of SHR2554 plus SHR1701 and the epigenetic modulating effect of SHR2554 in its combination with anti-PD-L1TGFβ antibody The exploratory objectives are to evaluate the pathological immunological or clinical predictive factors for efficacy and toxicity Based on the data of safety efficacy and recommended dose level obtained from phase Ⅰtrial this study moves into phase Ⅱ stage in which enrolled subjects are randomized to SHR2554 plus SHR 1701 or SHR1701 monotherapy to primarily evaluate the efficacy of SHR2554 plus SHR1701 and the epigenetic modulating effect of SHR2554 The second objectives include evaluating safety and other efficacy parameters such as overall response rate ORR disease control rate DCR duration of response DOR and overall survival OS The exploratory objectives are to evaluate laboratory predicting biomarkers
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None