Clinical trial NCT04068519: Study Investigating Safety, Tolerability, Pharmacokinetics (PK) and Antitumor Activities of Anti-PD-1 (Programmed Death-1) Monoclonal Antibody
Official title: Phase I/II Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activities of Anti-PD-1 Monoclonal Antibody BGB-A317 in Chinese Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2019-08-28
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

1. 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.
2. Participants must be able to provide archival tumor tissues (paraffin blocks or at least 10 unstained tumor specimen slides).
3. Participants must have at least one measurable lesion as defined per RECIST criterion version 1.1.
4. Participant must have adequate organ function.
5. 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.
6. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study.

Key Exclusion Criteria:

1. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
2. 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.
3. 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.
4. 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.
5. 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.
6. With uncontrollable pleural effusion, pericardial effusion or ascites requiring repeated drainage.
7. Use of any live or attenuated vaccines within 4 weeks (28 days) prior to initiation of study therapy.
8. Major surgical procedure (Grade 3 or 4) within the past 4 weeks (28 days) prior to study drug administration.
9. Prior allogeneic or solid organ transplantation.

NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Dose Verification and PK Sub-study: Number Participants With Adverse Events
timeFrame: Up to approximately 23 months
measure: Dose Verification: Recommended Dose of Tislelizumab
timeFrame: Up to approximately 23 months
measure: PK Sub-study: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Tislelizumab From Two Manufacturing Processes and Scales
timeFrame: 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
measure: 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
timeFrame: 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
measure: PK Sub-study: Maximum Observed Concentration (Cmax) of Tislelizumab From Two Manufacturing Processes and Scales
timeFrame: 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
measure: Indication Expansion: Objective Response Rate
timeFrame: Up to approximately 3 years and 5 months
Secondary outcomes:
measure: Dose Verification: Area Under the Concentration-time Curve From Time 0 to 21 Days Postdose (AUC0-tau) of Tislelizumab
timeFrame: 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)
measure: Dose Verification: Maximum Observed Concentration (Cmax) of Tislelizumab
timeFrame: 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)
measure: Dose Verification: Predose Plasma Concentration of Tislelizumab During Multiple Dosing (Ctrough)
timeFrame: 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)
measure: Dose Verification: Apparent Terminal Half-life of Tislelizumab (t1/2)
timeFrame: 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)
measure: Dose Verification: Clearance (Cl)
timeFrame: 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)
measure: Indication Expansion: Progression-free Survival (PFS)
timeFrame: Up to approximately 3 years and 5 months
measure: Indication Expansion: Duration of Response
timeFrame: Up to approximately 3 years and 5 months
measure: Indication Expansion: Clinical Benefit Rate
timeFrame: Up to approximately 3 years and 5 months
measure: Indication Expansion: Overall Survival
timeFrame: Up to approximately 3 years and 5 months
measure: Indication Expansion: Disease Control Rate
timeFrame: Up to approximately 3 years and 5 months
measure: Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab
timeFrame: Up to approximately 23 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat Sen University
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang University College of Medicine Second Affiliated Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.