Study Investigating Safety, Tolerability, Pharmacokinetics (PK) and Antitumor Activities of Anti-PD-1 (Programmed Death-1) Monoclonal Antibody

NCT04068519 | Completed Phase 1 Results

• 1 other identifier: BGB-A317-102
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 12

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (6)

• Dose Verification and PK Sub-study: Number Participants With Adverse Events

  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

  Up to approximately 23 months

• Dose Verification: Recommended Dose of Tislelizumab

  Recommended dose of tislelizumab for indication cohorts based on safety and tolerability

  Up to approximately 23 months

• PK Sub-study: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tislelizumab From Two Manufacturing Processes and Scales

  Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter final manufacturing process (FMP) were evaluated

  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

• 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

  Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter final manufacturing process (FMP) were evaluated

  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

• PK Sub-study: Maximum Observed Concentration (Cmax) of Tislelizumab From Two Manufacturing Processes and Scales

  Pharmacokinetics from products derived from two manufacturing scales at 500 liter and 2000 liter FMP were evaluated

  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

• Indication Expansion: Objective Response Rate

  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.

  Up to approximately 3 years and 5 months

Secondary Outcomes (11)

• 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: 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)

• 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)

• 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)

Study Arms (1)

Tislelizumab

EXPERIMENTAL

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.

Drug: Tislelizumab

Interventions

Tislelizumab DRUG

Administered intravenously

Also known as: BGB-A317

Tislelizumab

Eligibility Criteria

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

You may qualify if:

• 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.
• Participants must be able to provide archival tumor tissues (paraffin blocks or at least 10 unstained tumor specimen slides).
• Participants must have at least one measurable lesion as defined per RECIST criterion version 1.1.
• Participant must have adequate organ function.
• 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.
• Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BeiGene: lead

Study Sites (12)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)

Guangzhou, Guangdong, 510000, China

Location

Guangdong Provincial Peoples Hospital

Guangzhou, Guangdong, 510080, China

Location

The Fifth Affiliated Hospital Sun Yat Sen University

Zhuhai, Guangdong, 519000, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

The First Affiliated Hospital of Nanchang University Branch Donghu

Nanchang, Jiangxi, 330006, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

Location

Affiliated Zhongshan Hospital of Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Zhejiang University College of Medicine Second Affiliated Hospital

Hangzhou, Zhejiang, 310009, China

Location

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

Related Publications (3)

• Shen L, Guo J, Zhang Q, Pan H, Yuan Y, Bai Y, Liu T, Zhou Q, Zhao J, Shu Y, Huang X, Wang S, Wang J, Zhou A, Ye D, Sun T, Gao Y, Yang S, Wang Z, Li J, Wu YL. Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study. J Immunother Cancer. 2020 Jun;8(1):e000437. doi: 10.1136/jitc-2019-000437.

  PMID: 32561638 BACKGROUND

• Zhou Q et al. Efficacy and safety data from a Phase 1/2 trial of tislelizumab in Chinese patients with non-small cell lung cancer. North America Conference on Lung Cancer, October 2020.

  BACKGROUND

• Ye D, Desai J, Shi J, Liu SM, Shen W, Liu T, Shi Y, Wang D, Liang L, Yang S, Ma X, Jin W, Zhang P, Huang R, Shen Z, Zhang Y, Wu YL. Co-enrichment of CD8-positive T cells and macrophages is associated with clinical benefit of tislelizumab in solid tumors. Biomark Res. 2023 Mar 7;11(1):25. doi: 10.1186/s40364-023-00465-w.

  PMID: 36879284 DERIVED

MeSH Terms

Interventions

tislelizumab

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: August 28, 2019
• Study Start: December 28, 2016
• Primary Completion: December 1, 2018
• Study Completion: May 31, 2020
• Last Updated: October 26, 2024
• Results First Posted: November 30, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CN (12)