Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Participants With Advanced Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 12 April 2021
• Main ID: NCT02407990
• Date of registration: 26/03/2015
• Prospective Registration: Yes
• Primary sponsor: BeiGene
• Public title: Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Participants With Advanced Tumors
• Scientific title: A Phase 1A/1B, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activities of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Subjects With Advanced Tumors
• Date of first enrolment: June 2, 2015
• Target sample size: 451
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02407990
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Australia, Korea, Republic of, New Zealand, Taiwan, United States

Contacts

• Name: Jayesh Desai, MD
• Affiliation: Peter MacCallum Cancer Centre, Australia

Key inclusion & exclusion criteria

Key Inclusion Criteria:

1. Participants must have a histologically or cytologically confirmed advanced or
metastatic tumor for which no effective standard therapy is available.

1. For Phase 1A: no specific restriction

2. For Phase 1B: histology specified below

i. NSCLC (Participants with documented epidermal growth factor receptor (EGFR)
mutation or anaplastic lymphoma kinase (ALK) rearrangement should be excluded) ii.
ovarian cancer iii. gastric cancer iv. HCC (Barcelona-Clinic Liver Cancer stage C,
stage B not amenable to locoregional therapy or refractory to locoregional therapy,
and not amenable to a curative treatment approach, and Child-Pugh A) v. HNSCC vi.
esophageal carcinoma vii. Triple Negative Breast Cancer (TNBC) viii.
cholangiocarcinoma ix. Renal Cell Cancer (RCC), bladder cancer, melanoma, Merkel-cell
carcinoma, sarcoma, gastrointestinal stromal tumor (GIST), or Cutaneous squamous cell
carcinoma (cuSCC). Or any other solid tumors with known microsatellite
instability-high (MSI-H) or deficient MisMatch Repair (dMMR) status, such as
Colorectal Cancer (CRC) or pancreatic cancer

2. Participants with previously treated brain metastasis (es) that is asymptomatic or
radiographically/clinically stable and not requiring steroids medications for 4 weeks
prior to enrollment are permitted.

3. Participants must have archival tumor tissues or agree to a tumor biopsy for analysis
of predictive biomarkers such as PD-L1. (Fresh tumor biopsies are strongly recommended
at baseline for biomarker analysis in participants with readily accessible tumor
lesions and who consent to the biopsies.)

4. Participants must have measurable disease as defined per RECIST Version 1.1.

5. Male or female and =18 years of age on day of signing informed consent.

6. Eastern Cooperative Oncology Group (ECOG) performance status of =1.

7. Participants must have adequate organ function as indicated by the following
laboratory values.

- Absolute neutrophil count (ANC) =1,500 /mL

- Platelets =100,000 / mL

- Hemoglobin =9 g/dL or =5.6 mmol/L- without qualifications

- Serum creatinine =1.5 X upper limit of normal (ULN)

- Serum total bilirubin = 1.5 X ULN

- AST (SGOT) and ALT (SGPT) = 2.5 X ULN OR = 5 X ULN for participants with liver
metastases

- International Normalized Ratio (INR) or Prothrombin Time (PT) =1.5 X ULN

- Activated Partial Thromboplastin Time (aPTT) =1.5 X ULN

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 tumor for which a
participant is enrolled in the study, and locally curable cancers that have been
apparently cured, 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.

4. Participants who fail to meet enrollment criteria for other PD-1 or PD-L1 trials
solely due to low or negative predictive biomarkers.

5. Participants with active autoimmune diseases or history of autoimmune diseases should
be excluded.

6. Participants should be excluded if they have a condition requiring systemic treatment
with either corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days of study drug administration.

7. Has history of interstitial lung disease or non-infectious pneumonitis except for
those induced by radiation therapies..

8. Known history of Human Immunodeficiency Virus;

9. Active infection requiring therapy, positive tests for Hepatitis B surface antigen or
Hepatitis C ribonucleic acid (RNA) except in participant with HCC, who meet the
following criteria:

- HBV viral load (VL) <200 IU/mL (approximately 1000 cps/mL)

- Participants with active Hepatitis B Virus (HBV) infection need to be on anti-HBV
suppression =3 months, throughout treatment and for 6 months after

- Participants Hepatitis C Virus (HCV)-positive after successful treatment (defined
as sustained virologic response [SVR] 12 or SVR 24) are allowed as long as 4
weeks have passed between completion of HCV therapy and start of study drug

10. Use of any vaccines against infectious diseases (e.g., influenza, varicella, etc.)
within 4 weeks (28 days) of initiation of study therapy and 60 days after the last
administration of the study medication.

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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Advanced Cancer

Intervention(s)

Biological: BGB-A317

Primary Outcome(s)

Phase 1A: Number of participants with adverse events [Time Frame: From first dose to within 30 days of last dose of BGB-A317, up to 2 years and 1 month]

Phase 1B: Overall response based on RECIST v 1.1 in participants with select tumor types by the Investigators [Time Frame: Performed at an expected average of 10 weeks during treatment period (up to 2 years) and within 30 days of last dose of BGB-A317 during follow-up period]

Secondary Outcome(s)

Phase 1B: Plasma concentration [Time Frame: During first 4 months]

Phase 1A: Disease assessment by CT/MRI scan [Time Frame: Performed at an expected average of 10 weeks during treatment period (up to 2 years) and within 30 days of last dose of BGB-A317 during follow-up period]

Phase 1A: Area under the plasma concentration-time curve (AUC) [Time Frame: During first 4 months]

Phase 1A: Time to reach maximum plasma concentration (Tmax) [Time Frame: During first 4 months]

Phase 1B: Number of participants with adverse events [Time Frame: From first dose to within 30 days of last dose of BGB-A317, up to 2 years and 1 month]

Phase 1A: Anti-BGB-A317 antibody [Time Frame: Performed at an expected average of 6 weeks during treatment period (up to 2 years) and within 30 days of last dose of BGB-A317 during follow-up period]

Phase 1A: Terminal elimination half-life (t1/2) [Time Frame: During first 4 months]

Phase 1A: Maximum plasma concentration (Cmax) [Time Frame: During first 4 months]

Phase 1B: Disease assessment by CT/MRI scan [Time Frame: Performed at an expected average of 10 weeks during treatment period (up to 2 years) and within 30 days of last dose of BGB-A317 during follow-up period]

Secondary ID(s)

BGB-A317_Study_001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors