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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04068519
• Other study ID #: BGB-A317-102
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 28, 2016
• Est. completion date: May 31, 2020

Study information

• Verified date: February 2023
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: May 31, 2020
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

Drug:
• Tislelizumab
Administered intravenously

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	Guangdong general hospital	Guangzhou	Guangdong
China	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen university	Guangzhou	Guangdong
China	The Fifth Affiliated Hospital, Su-Sen University	Guangzhou	Guangdong
China	Sir Run Run Shaw hospital, School of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Zhejiang University school of Medicine	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Province hospital	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

References & Publications (2)

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. Erratum In: J Immunother Cancer. 2020 Jul;8(2): — View 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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Dose Verification: Recommended Dose of Tislelizumab	Recommended dose of tislelizumab for indication cohorts based on safety and tolerability	Up to approximately 23 months
Primary	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
Primary	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
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Indication Expansion: Progression-free Survival (PFS)	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.	Up to approximately 3 years and 5 months
Secondary	Indication Expansion: Duration of Response	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.	Up to approximately 3 years and 5 months
Secondary	Indication Expansion: Clinical Benefit Rate	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.	Up to approximately 3 years and 5 months
Secondary	Indication Expansion: Overall Survival	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.	Up to approximately 3 years and 5 months
Secondary	Indication Expansion: Disease Control Rate	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.	Up to approximately 3 years and 5 months
Secondary	Number of Participants With Positive Anti-drug Antibody (ADA) Status to Tislelizumab		Up to approximately 23 months