Combination treatment for advanced solid tumors and B-cell lymphomas

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

This study is testing a new combination of two treatments for patients with advanced solid tumors and B-cell lymphomas to see if it is safe and effective after other treatments have not worked.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: prednisone, immunotherapy
• Locations: 1 site (Beijing)
• Trial ID: NCT04407741 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of combining the EZH2 inhibitor SHR2554 with the anti-PD-L1/TGFβ antibody SHR1701 in patients with advanced solid tumors and B-cell lymphomas. The first phase focuses on assessing the safety and feasibility of this combination in patients who have already undergone treatment. The second phase aims to evaluate the effectiveness of this combination therapy and its impact on the tumor microenvironment. The study targets patients with specific types of cancer that have shown resistance to previous therapies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with advanced solid tumors or B-cell lymphomas that have not responded to prior treatments.

Not a fit: Patients with tumors that are not advanced or those who have not received prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with advanced solid tumors and B-cell lymphomas by enhancing the effectiveness of immunotherapy.

How similar studies have performed: Other studies have shown promise in combining EZH2 inhibitors with immunotherapy, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 1. Age from 18 to 70 years with estimated life expectancy \>3 months.
* 2. 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).
* 3. Have at least one measurable target lesion, determined by the site study team based on RECIST 1.1 and immune related RECIST.
* 4. 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.
* 5. 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.
* 6. Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 1 at the time of enrollment.
* 7. 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.
* 8. Previous treatment with anti-PD-1/PD-L1 antibodies or cytotoxic T lymphocyte associated antigen 4 (CTLA-4) inhibitors are allowed.
* 9. Ability to understand and sign a written informed consent document.
* 10.Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 90 days after the last dose of the drug.

Exclusion Criteria:

* 1. Active, known or suspected autoimmune diseases.
* 2. 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.
* 3. Subjects are being treated with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
* 4. History of severe hypersensitive reactions to other monoclonal antibodies.
* 5. History of allergy or intolerance to study drug components.
* 6. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
* 7. History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
* 8. 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.
* 9. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
* 10. 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.
* 11. 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 \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
* 12. Vaccination within 30 days of study enrollment.
* 13. Active bleeding or known hemorrhagic tendency.
* 14. Subjects with unhealed surgical wounds for more than 30 days.
* 15. Being participating any other trials or withdraw within 4 weeks.

Where this trial is running

Beijing

• Department of Biotherapeutic, Chinese PLA General Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Weidong Han, PhD

Conditions Solid Tumor; Lymphoma; Anti-PD-L1/TGFβ; EZH2; SHR2554; SHR1701; Advanced