Phase Ⅰ/Ⅱ Study of SHR2554 in Combination With SHR1701 in Patients With Advanced Solid Tumors and B-cell Lymphomas

NCT04407741 | Unknown Phase 1 DMC

• 1 other identifier: CHN-PLAGH-BT-055
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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-L1/TGFβ) blockade may 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 phase Ⅱ stage of this study is to primarily evaluate the efficacy of SHR2554 plus SHR1701 and the epigenetic modulating effect of SHR2554.

Conditions

Solid Tumor; Lymphoma

Keywords

Anti-PD-L1/TGFβ; EZH2; SHR2554; SHR1701; Advanced

Outcome Measures

Primary Outcomes (1)

• Median amount of time subject survives without disease progression following the initiation of treatment

  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.

  up to 36 months

Secondary Outcomes (3)

• Number of subjects with treatment related adverse events as assessed by CTCAE v5.0.

  Up to 90 days after the last dose of study drugs.

• The percentage of subjects respond to treatment.

  up to 36 months

• Median amount of times subjects alive after treatment

  up tp 36 months

Study Arms (2)

SHR2554+ SHR1701

EXPERIMENTAL

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

Drug: SHR2554+SHR1701

SHR1701

EXPERIMENTAL

Drug: SHR1701 30mg/kg IV over 30 minutes on day 1, every 3 weeks

Drug: SHR1701

Interventions

SHR2554+SHR1701 DRUG

SHR2554: recommended dose from phase I trial, PO, twice a day. SHR1701: 30mg/kg, IV, over 30 minutes

SHR2554+ SHR1701

SHR1701 DRUG

SHR1701: 30mg/kg, IV, over 30 minutes

SHR1701

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age from 18 to 70 years with estimated life expectancy \>3 months.
• \. Histopathological confirmed locally advanced or metastatic systematically pretreated epidermal growth factor receptor (EGFR) / anaplastic lymphoma kinase (ALK) / c-ros oncogene 1 receptor kinase (ROS1) /BRAF negative non-small cell lung cancer (adenocarcinoma or squamous cell carcinoma), pancreatic adenocarcinoma, cholangiocarcinoma, gastrointestinal adenocarcinoma, triple-negative breast cancer and relapsed/refractory B-cell lymphoma (All enrolled subjects with above solid carcinoma are required to have received at least first-line systematic therapy and subjects with R/R B-cell lymphoma need a history of at least two lines of previous treatment; For solid carcinoma subjects enrolled in phase Ⅱ period, their previous treatment lines are limited to no more than four lines; Besides previously treated subjects, subjects with initially diagnosed pancreatic adenocarcinoma or cholangiocarcinoma are also eligible for enrollment in phase Ⅱ period).
• \. Have at least one measurable target lesion, determined by the site study team based on RECIST 1.1 and immune related RECIST.
• \. Fresh tumor samples or formalin-fixed paraffin embedded tumor archival samples within 3 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor re-biopsy in the process of this study.
• \. Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to \<= grade 1 toxicity.
• \. Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 1 at the time of enrollment.
• \. Have adequate organ function, as defined in the table below, which should be confirmed within 2 weeks prior to the first dose of study drugs.
• Leukocytes greater than or equal to 3.0 ×10\^9/L.
• Absolute neutrophil counts greater than or equal to 1.0 ×10\^9/L.
• Platelets greater than or equal to 100 ×10\^9/L.
• Hemoglobin greater than or equal to 90 g/L.
• Total bilirubin less than or equal to 2 x ULN.
• Serum albumin should be no less than 30 g/L.
• Alanine aminotransferase or Aspartate aminotransferase less than 2 x Upper Limit of Normal (ULN).
• Measured creatinine clearance ≥ 60 mL per min.

You may not qualify if:

• \. Active, known or suspected autoimmune diseases.
• \. Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
• \. Subjects are being treated with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
• \. History of severe hypersensitive reactions to other monoclonal antibodies.
• \. History of allergy or intolerance to study drug components.
• \. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
• \. History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
• \. Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
• \. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
• \. Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.
• \. Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
• \. Vaccination within 30 days of study enrollment.
• \. Active bleeding or known hemorrhagic tendency.
• \. Subjects with unhealed surgical wounds for more than 30 days.
• \. Being participating any other trials or withdraw within 4 weeks.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Department of Biotherapeutic, Chinese PLA General Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Lymphoma

Interventions

SHR-1701

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Weidong Han, PhD

  Department of Bio-therapeutic, Chinese PLA General Hospital

  STUDY DIRECTOR

Central Study Contacts

Weidong Han, PhD

CONTACT

+86-10-66937463; hanwdrsw@sina.com

Kaichao Feng, MD

CONTACT

+86-10-55499341; timothyfkc@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Bio-therapeutic Department, Professor

Model Details: 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.

Study Record Dates

• First Submitted: May 20, 2020
• First Posted: May 29, 2020
• Study Start: September 1, 2020
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: December 12, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)