Study Investigating Safety, Tolerability, Pharmacokinetics (PK) and Antitumor Activities of Anti-PD-1 (Programmed Death-1) Monoclonal Antibody
- Registration Number
- NCT04068519
- Lead Sponsor
- BeiGene
- Brief Summary
This was a dose verification, pharmacokinetic (PK) assessment of products derived from two manufacturing processes and scales (500L-FMP and 2000L-FMP; FMP: Final Manufacturing Process) and indication expansion clinical study of monoclonal antibody conducted in Chinese subjects with advanced solid tumors, with a purpose of exploring the safety, tolerability, pharmacokinetics and preliminary efficacy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 300
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Participants must have histologically or cytologically confirmed advanced or metastatic tumors (unresectable), have had progression or intolerability since last standard anti-tumor treatment, or have no standard treatment or have refused standard therapy.
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Participants must be able to provide archival tumor tissues (paraffin blocks or at least 10 unstained tumor specimen slides).
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Participants must have at least one measurable lesion as defined per RECIST criterion version 1.1.
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Participant must have adequate organ function.
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Females are eligible to participate in the study if they are:
a) Non-childbearing potential (that is, physiologically incapable of becoming pregnant) who:
- Has had hysterectomy
- Has had bilateral oophorectomy
- Has had bilateral tubal ligation or are post-menopausal (total cessation of menses for ≥1 year) b) Childbearing potential:
- Must be willing to use a highly effective method of birth control for the duration of the study, and for at least 120 days after the last dose of tislelizumab, and have a negative urine or serum pregnancy test within 7 days of the first dose of study drug.
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Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study.
Key
- History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
- Prior malignancy active within the previous 2 years except for the tumor under investigation in this trial, cured or locally curable cancers, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
- Prior therapies targeting PD-1 or PD-L1. Active brain or leptomeningeal metastases. Participants with brain metastases are permitted if they are asymptomatic, for example, diagnosed incidentally by brain imaging, or participants with previously treated brain metastases that are asymptomatic at screening, radiographically stable and not requiring steroid medications for at least 4 weeks prior to the first administration of study treatment.
- Participants with active autoimmune diseases or history of autoimmune diseases or immunodeficiency that may relapse should be excluded. Participants with following diseases are allowed to be enrolled for further screening: type I diabetes, hypothyroidism managed with hormone replacement therapy only, skin diseases not requiring systemic treatment (such as vitiligo, psoriasis or alopecia), or diseases not expected to recur in the absence of external triggering factors.
- Participants should be excluded if they have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration.
- With uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage.
- Use of any live or attenuated vaccines within 4 weeks (28 days) prior to initiation of study therapy.
- Major surgical procedure (Grade 3 or 4) within the past 4 weeks (28 days) prior to study drug administration.
- Prior allogeneic or solid organ transplantation.
NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tislelizumab Tislelizumab Tislelizumab 200 mg intravenously (IV) once every 3 weeks (21 days per cycle) until no evidence of continued clinical benefits, unacceptable toxicity, or withdrawal of informed consent at the discretion of the investigator. There were 3 parts in this study: dose verification, pharmacokinetic (PK) sub-study, and indication expansion.
- Primary Outcome Measures
Name Time Method Dose Verification and PK Sub-study: Number Participants With Adverse Events Up to approximately 23 months Number of participants with adverse events (AEs) and serious adverse events (SAEs), as defined per NCI-CTCAE Version 4.03, including physical examination, electrocardiograms and laboratory assessments
Dose Verification: Recommended Dose of Tislelizumab Up to approximately 23 months Recommended dose of tislelizumab for indication cohorts based on safety and tolerability
PK Sub-study: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tislelizumab From Two Manufacturing Processes and Scales Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter final manufacturing process (FMP) were evaluated
PK Sub-study: Area Under the Concentration-time Curve From Time 0 to 28 Days Postdose (AUC0-28d) of Tislelizumab From Two Manufacturing Processes and Scales Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter final manufacturing process (FMP) were evaluated
PK Sub-study: Maximum Observed Concentration (Cmax) of Tislelizumab From Two Manufacturing Processes and Scales Predose, end of infusion, 3 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, and Day 29 predose Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter FMP were evaluated
Indication Expansion: Objective Response Rate Up to approximately 3 years and 5 months Objective response rate (ORR) is defined as the percentage of participants who achieved objective tumor response (complete response or partial response) according to RECIST Version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
- Secondary Outcome Measures
Name Time Method Dose Verification: Predose Plasma Concentration of Tislelizumab During Multiple Dosing (Ctrough) Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle) Indication Expansion: Progression-free Survival (PFS) Up to approximately 3 years and 5 months Progression-free survival is defined as the time from the date of first study dose to disease progression or death, whichever comes first, as determined by Investigator per RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Dose Verification: Area Under the Concentration-time Curve From Time 0 to 21 Days Postdose (AUC0-tau) of Tislelizumab Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle) Dose Verification: Maximum Observed Concentration (Cmax) of Tislelizumab Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle) Dose Verification: Apparent Terminal Half-life of Tislelizumab (t1/2) Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 and Cycle 5 (21 days per cycle) Indication Expansion: Duration of Response Up to approximately 3 years and 5 months Duration of response for responders with complete or partial response is defined as the time interval between the date of the earliest qualifying response and the date of progressive disease or death for any cause, whichever occurs earlier as determined by Investigator per RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Indication Expansion: Clinical Benefit Rate Up to approximately 3 years and 5 months Clinical benefit rate is defined as the percentage of participants in specific tumor types reaching confirmed CR, PR and durable stable disease (SD; at ≥ 24 weeks) in accordance with RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Indication Expansion: Overall Survival Up to approximately 3 years and 5 months Overall survival is defined as the time from the date of the first study dose to death. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Indication Expansion: Disease Control Rate Up to approximately 3 years and 5 months Disease control rate is defined as the percentage of participants reaching CR, PR, and SD according to RECIST version 1.1. Indication expansion includes participants from all parts in the following indications: non-small cell lung cancer (NSCLC), melanoma, esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), urothelial carcinoma (UC), nasopharyngeal carcinoma (NPC), renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors, and other tumor types.
Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab Up to approximately 23 months Dose Verification: Clearance (Cl) Predose, end of infusion, 1.5 hours, 6 hours on Day 1, Day 2, Day 4, Day 8, Day 15, Day 22 predose in Cycle 1 (21 days per cycle)
Trial Locations
- Locations (12)
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
🇨🇳Guangzhou, Guangdong, China
Guangdong Provincial Peoples Hospital
🇨🇳Guangzhou, Guangdong, China
The Fifth Affiliated Hospital Sun Yat Sen University
🇨🇳Zhuhai, Guangdong, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
Affiliated Zhongshan Hospital of Fudan University
🇨🇳Shanghai, Shanghai, China
Zhejiang University College of Medicine Second Affiliated Hospital
🇨🇳Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China