Efficacy of Tislelizumab and Spartalizumab in Patients with PD1-High mRNA Expressing Metastatic Tumors: A Multicancer-Type Clinical Trial
- Trial ID
- 2023-508549-41-00
- Sponsor
- Solti Group
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the study is to assess the **efficacy** of tislelizumab across multiple cancer types in patients with high mRNA PD1 expressing tumors, defined by a single and pre-specified cut-off. This is clinically relevant as it aims to evaluate the potential of tislelizumab in targeting PD1-high tumors, which could lead to improved treatment outcomes for patients with metastatic disease.
Secondary objectives include:
- Determining the clinical benefit of tislelizumab in patients with high mRNA PD1 expressing tumors (Cohort 3).
- Determining the clinical benefit of spartalizumab in patients with high and low mRNA PD1-expressing tumors (Cohort 1 and 2, respectively).
- Assessing the safety and tolerability of spartalizumab and tislelizumab.
Participants
The clinical trial involves participants diagnosed with **metastatic disease** and aims to assess the efficacy of tislelizumab in patients with high mRNA PD1 expressing tumors. The study population includes both male and female participants aged 18 years and older, with the possibility of enrolling individuals over 75 years following consultation with the study medical monitor. Participants are required to have a life expectancy of more than three months and measurable disease based on RECIST 1.1 or RANO criteria. The trial includes individuals with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and adequate organ function. Participants may have received up to three lines of prior standard chemotherapy in the inoperable or metastatic setting. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **tislelizumab** and **spartalizumab** in patients with metastatic disease characterized by high mRNA PD1 expression. This is a Phase II, randomized, double-blind, controlled trial. The trial commenced on April 30, 2021, with an estimated completion date of July 31, 2025. The trial involves multiple study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, including age, disease progression, and organ function. Participants are required to have a histologically confirmed diagnosis of PD1 mRNA high-expression or low-expression, depending on the cohort, and must provide informed consent.
Following the screening, participants will undergo regular follow-up visits to monitor treatment response and safety. These visits will assess the primary endpoint, which is the Overall Response Rate (ORR) defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include Clinical Benefit Rate (CBR), Progression-Free Survival (PFS), Duration of Response (DoR), Time to Response (TtR), and Overall Survival (OS). The trial will also monitor the incidence and severity of Treatment Emergent Adverse Events (TEAEs) according to the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5.
The expected duration of participant involvement is up to four years, with treatment administered intravenously. Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or withdrawal of consent. The trial aims to provide comprehensive data on the efficacy and safety of the investigational products, contributing to the understanding of their potential benefits in treating metastatic disease with high PD1 expression.
Treatment
The clinical trial involves the administration of **Tevimbra**, a 100 mg concentrate for solution for infusion, containing the active substance **tislelizumab**. This pharmaceutical form is a solution for infusion, intended for **intravenous use**. The maximum daily dose is 300 mg, with a total dose not exceeding 300 mg per administration. The treatment period is set for a maximum of 4 cycles, with each cycle corresponding to a specific time unit. The product is manufactured by BeiGene Ireland Limited and is not a paediatric formulation. The administration of Tevimbra is monitored to ensure compliance with the dosing schedule and to assess the efficacy across multiple cancer types in patients with high mRNA PD1 expressing tumors.
Another experimental medication used in the trial is **PDR001**, a concentrate for solution for infusion containing the active substance **spartalizumab**. This product is also administered via **intravenous use**. The maximum daily dose for PDR001 is 400 mg, with a total dose not exceeding 400 mg per administration. The treatment period is similarly set for a maximum of 4 cycles. PDR001 is produced by Novartis Pharma AG and is not formulated for paediatric use. The administration of PDR001 is carefully monitored to ensure adherence to the dosing regimen and to evaluate its efficacy in the specified patient cohort.
Both Tevimbra and PDR001 are administered as part of the clinical trial to assess their efficacy in treating patients with high mRNA PD1 expressing tumors. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Compliance with the dosing schedule is monitored throughout the trial to ensure accurate assessment of the treatment outcomes.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the **Overall Response Rate (ORR)**, which is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by local investigators. Secondary endpoints include the Clinical Benefit Rate (CBR), Progression-Free Survival (PFS), Duration of Response (DoR), Time to Response (TtR), and Overall Survival (OS). These endpoints will be evaluated based on local investigator assessments using RECIST v1.1 criteria.
The Clinical Benefit Rate (CBR) is defined as the proportion of patients with a best overall response of CR, PR, or stable disease (SD) lasting at least 24 weeks. Progression-Free Survival (PFS) is measured from the time of allocation to the first occurrence of disease progression or death from any cause. Duration of Response (DoR) is the time from the first documented objective response to disease progression or death. Time to Response (TtR) is the time from allocation to the first objective tumor response observed for patients achieving CR or PR. Overall Survival (OS) is defined as the time from allocation to death from any cause and will be determined at the end of the study.
These efficacy parameters will be collected and analyzed at various time points throughout the trial, with assessments conducted by local investigators. The trial will utilize the RECIST v1.1 criteria to ensure standardized evaluation of tumor responses. The study is designed to assess the efficacy of **tislelizumab** and **spartalizumab** across multiple cancer types in patients with high mRNA PD1 expressing tumors, with the trial phase categorized as Phase II.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of PD1 mRNA high-expression (cohorts 1 and 3) or PD1 mRNA lowexpression (cohort 2) determined on the tumor sample will be enrolled in this study. Enrollment of patients > 75 years of age is allowed after consultation and approval of the study medical monitor.
- Life expectancy > 3 months as per investigator opinion.
- The participant (or legally acceptable representative if applicable) provides written specific informed consent for the remaining screening tests and study procedures before inclusion in the trial.
- Have measurable disease based on RECIST 1.1 or RANO criteria, as appropriate to tumor type. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Note: Patient with primary central nervous system should meet the following criterion: a. Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice
- Have radiologic evidence of disease progression or recurrence after the previous oncologic treatment.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Evaluation of ECOG is to be performed within 10 days prior to the date of allocation.
- Have adequate organ function as per protocol defined. Specimens must be collected within 28 days prior to the start of study treatment.
- Patients could have received a maximum of 3 lines of prior standard of care chemotherapy in the inoperable/metastatic setting. Note: A chemotherapy line in advanced disease is an anticancer regimen(s) that contains at least 1 cytotoxic chemotherapy agent and given for 28 days or longer. If a cytotoxic chemotherapy regimen was discontinued for a reason other than disease progression and lasted less than 28 days, then this regimen does not count as a "prior line of chemotherapy". Targeted agents (such as CDK 4/6 inhibitos, mTOR inhibitor, PARP inhibitors) endocrine therapies, on their own no contribute to the count of a prior line of the chemotherapy; however, regimens with such agents in combination with cytotoxic chemotherapy should be classified as one line of chemotherapy
- Treatment-related toxicities (except alopecia) must ≤ Grade 1 at the time of allocation according to CTCAE version 5.0.
Exclusion Criteria
- A Women of childbearing potential who has a positive urine pregnancy test within 72 hours prior to allocation.
- Has received prior therapy with an anti-PD1, anti-PDL1, or anti PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
- Has received prior systemic anti-cancer therapy, including investigational agents within 2 weeks.
- Has received prior radiotherapy within 2 weeks of start of study treatment.
- Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment. Note: It is not recommended the use of live or attenuated COVID-19 vaccines within 4 weeks of initiation or during study treatment. However, if vaccination with these vaccines is required, please ask for advice on how to proceed the Medical Monitor
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 2 weeks prior to the first dose of study treatment.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
- Patients with thymoma are not eligible. Patients with active CNS metastases and/or carcinomatous meningitis are not eligible.
- Has severe hypersensitivity (≥Grade 3) to Spartalizumab/ tislelizumab and/or any of its excipients.
- History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). For more information, see appendix 2.
- Prior allogeneic stem cell transplantation or organ transplantation
- Has a history of interstitial lung disease, (non-infectious) pneumonitis that required steroids or has current pneumonitis, uncontrolled lung including pulmonary fibrosis, acute lung diseases, etc. Patients with significantly impaired pulmonary function, or who require supplemental oxygen at baseline must undergo an assessment of pulmonary function at screening
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV).
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection.
- Has a known history of active TBC (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 150 days after the last dose of trial treatment.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 150- days after stopping treatment with spartalizumab /tislelizumab
- Sexually active males, unless they use a condom during intercourse while on treatment and for 150 days after stopping treatment with spartalizumab/tislelizumab should not father a child in this period. A condom is required to be used by vasectomized men as well during intercourse in order to prevent delivery of the drug via semen.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 02 Jun 2021 | 184 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Tevimbra 100 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 300 | 4 | PRD11015698 |
Tevimbra 100 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 300 | 4 | PRD11015699 |
PDR001 | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 400 | 4 | PRD6759834 |
Tevimbra 100 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 300 | 4 | PRD11015696 |
Tevimbra 100 mg concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 300 | 4 | PRD11015697 |