Phase Ⅰ/Ⅱ Study of SHR2554 in Combination With SHR1701 in Patients With Advanced Solid Tumors and B-cell Lymphomas
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04407741|
Recruitment Status : Recruiting
First Posted : May 29, 2020
Last Update Posted : September 23, 2020
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor Lymphoma||Drug: SHR2554+SHR1701 Drug: SHR1701||Phase 1 Phase 2|
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-L1/TGFβ) 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-L1/TGFβ 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-L1/TGFβ 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||In phase I period, patients that meet inclusion and exclusion criteria are enrolled to evaluate the safety, feasibility and pharmacokinetics of SHR2554 plus SHR1701. In the following phase II period, based on the recommended dose level from phase I study, enrolled patients are randomized to trial group (SHR2554 plus SHR1701) and control group (SHR1701) to assess the clinical efficacy of SHR2554 plus SHR1701 and immunomodulating effect of SHR2554 to SHR1701 in each cohort.|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label Phase Ⅰ/Ⅱ Study of EZH2 Inhibitor SHR2554 in Combination With Anti-PD-L1/TGFβ Antibody SHR1701 in Patients With Advanced or Metastatic Solid Tumors and Relapsed/Refractory B-cell Lymphomas|
|Actual Study Start Date :||September 1, 2020|
|Estimated Primary Completion Date :||June 1, 2022|
|Estimated Study Completion Date :||June 1, 2023|
Experimental: SHR2554+ SHR1701
Drug: SHR2554 recommended dose from phase Ⅰstudy, PO, twice a day, every 3 weeks SHR1701 30mg/kg IV over 30 minutes on day 1, every 3 weeks
SHR2554: recommended dose from phase I trial, PO, twice a day. SHR1701: 30mg/kg, IV, over 30 minutes
Drug: SHR1701 30mg/kg IV over 30 minutes on day 1, every 3 weeks
SHR1701: 30mg/kg, IV, over 30 minutes
- Median amount of time subject survives without disease progression following the initiation of treatment [ Time Frame: up to 36 months ]The primary endpoint is progression free survival (PFS) after treatment. PFS is defined as the time from first treatment to the date of the first documented tumor progression or death due to any cause.
- Number of subjects with treatment related adverse events as assessed by CTCAE v5.0. [ Time Frame: Up to 90 days after the last dose of study drugs. ]Establishing the safety profile following the initiation of treatment and grading these toxicities by CTCAE v5.0
- The percentage of subjects respond to treatment. [ Time Frame: up to 36 months ]Overall response rate is defined as the sum of partial responses and complete responses.
- Median amount of times subjects alive after treatment [ Time Frame: up tp 36 months ]The median overall survival (OS) time is defined as the time from enrollment to the date of death.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04407741
|Contact: Weidong Han, PhDemail@example.com|
|Contact: Kaichao Feng, MDfirstname.lastname@example.org|
|Department of Biotherapeutic, Chinese PLA General Hospital||Recruiting|
|Contact: KAICHAO FENG, MD +86-10-55499341 email@example.com|
|Study Director:||Weidong Han, PhD||Department of Bio-therapeutic, Chinese PLA General Hospital|