Advanced or Recurrent Solid Tumors
Conditions
Keywords
solid tumor, tumor vaccine, immune checkpoint inhibitor
Brief summary
The goal of this clinical trial is to learn the side effects, safety and effect of a tumor vaccine (EVM16) alone or in combined with an anti-PD-1 antibody (tislelizumab) . This clinical trial will include solid tumor patients who failed standard treatment. The main questions to answer are: Safety of EVM16. Suitable dose of EVM16. Effects of EVM16 combined with tislelizumab.
Interventions
BIOLOGICALEVM16
cancer vaccine
DRUGTislelizumab
Anti-PD1 antibody
Sponsors
Peking University
Shanghai Cancer Centre
Everest Medicines (China) Co.,Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Immunogenicity, and Initial Efficacy of EVM16 Injection as a Single and Combination with Tislelizumab in Subjects with Advanced or Recurrent Solid Tumors.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Recurrent or metastatic solid tumors that have been histologically or cytologically pathologically confirmed and are not amenable to radical treatment with surgery or local therapy. * Patients with advanced or recurrent solid tumors who have failed prior standard therapy. * Expected survival period \>6 weeks at the time of informed consent. * Adequate organ function * Eastern Cooperative Oncology Group (ECOG) Physical Status Score 0 to 1. * Is willing to provide archival or fresh tumor tissue samples for EVM16 production. * Has adequate treatment washout period prior to first study dose. * Has at least one measurable lesion as assessed by the investigator according to RECIST version 1.1 criteria before enrollment. Key
Exclusion criteria
* Primary central nervous system (CNS) malignancies that are symptomatic, untreated, or in need of curative treatment, or subjects with CNS metastases. * Uncontrolled co-morbidities. * Cerebrovascular event (stroke, transient ischemic attack, etc.) within 4 months prior to the signing of inform consent form. * In screening period male QTcF interval \>450 ms; Female QTcF interval \>470 ms (calculated by the Fridericia formula). * Left ventricular ejection fraction (LVEF) \< 50% during the screening period. * Diagnosis of immunodeficiency, or history or syndrome of active as well as former autoimmune disease with risk of relapse, or a disease requiring systemic steroid hormone or immunosuppressive drug therapy. * Subjects with a history of positive human immunodeficiency virus (HIV) test or acquired immunodeficiency syndrome (AIDS). * Co-infection HBV and HCV. * Presence of any active infection requiring systemic therapy. * Patients who are still on any other investigational medications treatment at the time of screening. * Previous treatment with cell therapy, tumor vaccines, cytokines, or growth factors for cancer control. * Patients with prior intolerance to tislelizumab resulting in permanent termination of tislelizumab. * History or presence of significant lung disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| safety and tolerability | From the first study intervention to 90 days after the last study intervention. | The incidence and severity of adverse events (AEs) and serious adverse events (SAEs), the incidence of dose-limiting toxicity (DLT) （only in phase Ia）, and the incidence of AEs of grade 3 or higher were assessed according to the NCI CTCAE v5.0 in the treatment of EVM16 alone as well as EVM16 in combination with Tislelizumab. |
| RP2D for EVM16 | During the intervention, up to approximately 1 year. | Based on safety, tolerability, immunogenicity to determine RP2D. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| immunogenicity of EVM16 | during the intervention, up to 1 year | Based on proportion of IFN-γ-positive T cells and/or T cell receptor sequences after EVM16 administration to assess the immunogenicity of EVM16 in subjects with advanced or recurrent solid tumours. |
| objective response rate (ORR) of EVM16 in combination with tislelizumab | From date of first study dose until the date of disease progression, or until the patient start subsequent anti-cancer treatment, or death, or lost to follow up or the study ends, whichever occurs first. | Proportion of patients with partial response (PR) and complete response (CR) as assessed by the investigators according to RECIST v1.1 in EVM16 combined with tislelizumab arm. |
| disease control rate (DCR) of EVM16 in combination with tislelizumab | From date of first study dose until the date of disease progression, or until the patient start subsequent anti-cancer treatment, or death, or lost to follow up or the study ends, whichever occurs first. | Proportion of patients with partial response (PR) , complete response (CR) and stable disease (SD) as assessed by the investigators according to RECIST v1.1 in EVM16 combined with tislelizumab arm. |
| duration of disease remission (DOR) of EVM16 in combination with tislelizumab | From date of first study dose until the date of disease progression, or until the patient start subsequent anti-cancer treatment, or death, or lost to follow up or the study ends, whichever occurs first. | Duration of objective response (PR and CR) as assessed by the investigators according to RECIST v1.1 in EVM16 combined with tislelizumab arm. |
| time to remission (TTR) of EVM16 in combination with tislelizumab | From date of first study dose until the date of disease progression, or until the patient start subsequent anti-cancer treatment, or death, or lost to follow up or the study ends, whichever occurs first. | Time from enrollment to objective response (PR and CR) as assessed by the investigators according to RECIST v1.1 in EVM16 combined with tislelizumab arm. |
| PFS of EVM16 in combination with tislelizumab （Only in phase Ib） | From date of first study dose until the date of disease progression, or until the patient start subsequent anti-cancer treatment, or death, or lost to follow up or the study ends, whichever occurs first | Progression-free survival (PFS) as assessed by the investigators according to RECIST v1.1 in EVM16 combined with tislelizumab arm. |
Countries
China
Contacts
CONTACTLin Shen, MD
CONTACTYanshuo Cao, MD
PRINCIPAL_INVESTIGATORLin Shen, MD
Peking University Cancer Hospital & Institute
Outcome results
None listed