Phase 1
Completed N=451
Study of the Safety, Pharmacokinetics and Antitumor Activities of BGB-A317 in Participants With Advanced Tumors
Source: ClinicalTrials.gov NCT02407990 ↗Enrolled (actual)
451
Serious AEs
37.9%
Results posted
Nov 2021
Primary outcomePrimary: Phase 1A: Number of Participants Experiencing Adverse Events (AEs) — 114 Participants
Summary
This study evaluated the safety, tolerability, pharmacokinetic profile and treatment effect of a new drug known as BGB-A317 in participants with advanced tumors.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1A: Number of Participants Experiencing Adverse Events (AEs) |
114 | — |
| PRIMARY Phase 1A: Number Of Participants With Abnormal Physical Examination Values |
1; 6; 0; 9; 17; 5 | — |
| PRIMARY Phase 1A: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings |
— | — |
| PRIMARY Phase 1A: Number Of Participants With Abnormal Electrocardiograms |
31; 9; 3; 73; 35; 8 | — |
| PRIMARY Phase 1A: Number Of Participants With Abnormal Laboratory Values |
6; 11; 7; 5; 7; 7 | — |
| PRIMARY Phase 1A: Number Of Participants Experiencing Severe AEs |
14 | — |
| PRIMARY Phase 1B: Objective Response Rate (ORR) |
11.6 | — |
| SECONDARY Phase 1A: Area Under The Plasma Concentration-time Curve Within the Dosing Interval (AUC0-tau) For Tislelizumab |
84.92; 332.2; 811.8; 1916.0; 512.1; 1219.0 | — |
| SECONDARY Phase 1A: Maximum Observed Plasma Concentration (Cmax) For Tislelizumab |
13.5; 48.3; 147.0; 278.0; 56.8; 130.0 | — |
| SECONDARY Phase 1A: Time To Maximum Concentration (Tmax) For Tislelizumab |
3.46; 2.39; 2.48; 2.43; 1.57; 4.95 | — |
| SECONDARY Phase 1A: Half-life (T½) For Tislelizumab |
10.7; 12.9; 15.0; 14.5; 17.1; 19.6 | — |
| SECONDARY Phase 1A - Part 3: Clearance (Cl) For Tislelizumab |
0.186 | — |
| SECONDARY Phase 1A/1B: Number Of Participants With Anti-drug Antibodies (ADAs) |
1; 6; 5; 1; 6; 43 | — |
| SECONDARY Phase 1A: ORR |
18.1 | — |
| SECONDARY Phase 1A: CR Rate |
6 | — |
| SECONDARY Phase 1A: PR Rate |
15 | — |
| SECONDARY Phase 1A: Stable Disease (SD) Rate |
42 | — |
| SECONDARY Phase 1A: Progression-free Survival (PFS) |
3.5 | — |
| SECONDARY Phase 1A: Overall Survival (OS) |
13.6 | — |
| SECONDARY Phase 1A: Duration Of Response (DOR) |
14.6 | — |
| SECONDARY Phase 1B: Number of Participants Experiencing AEs |
322 | — |
| SECONDARY Phase 1B: Steady State Plasma Trough Concentration Of Tislelizumab |
63.9; 90.4; 40.7; 54.4; 77.4; 57.8 | — |
| SECONDARY Phase 1B: PFS |
2.1 | — |
| SECONDARY Phase 1B: Disease Control Rate (DCR) |
41.2 | — |
| SECONDARY Phase 1B: Clinical Benefit Rate (CBR) |
24.5 | — |
| SECONDARY Phase 1B: Number Of Participants With Abnormal Physical Examination Values |
5; 26; 1; 24; 30; 12 | — |
| SECONDARY Phase 1B: Number Of Participants Experiencing Dose-dependent Toxicity Through Ophthalmology Findings |
— | — |
| SECONDARY Phase 1B: Number Of Participants With Abnormal Electrocardiograms |
84; 24; 10; 241; 67; 22 | — |
| SECONDARY Phase 1B: Number Of Participants With Abnormal Laboratory Values |
21; 42; 21; 21; 22; 12 | — |
| SECONDARY Phase 1B: Number Of Participants Experiencing Severe AEs |
27 | — |
Eligibility Criteria
Key Inclusion Criteria
- Participants must have had a histologically or cytologically confirmed advanced or metastatic tumor for which no effective standard therapy was available.
- For Phase 1A: no specific restriction
- For Phase 1B: histology specified below:
i. non-small cell lung cancer (participants with documented epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangement should have been excluded) ii. ovarian cancer iii. gastric cancer iv. hepatocellular carcinoma (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. head and neck squamous cell carcinoma vi. esophageal carcinoma vii. triple negative breast cancer viii. cholangiocarcinoma ix. renal cell cancer, bladder cancer, melanoma, Merkel-cell carcinoma, sarcoma, gastrointestinal stromal tumor, or cutaneous squamous cell carcinoma. Or any other solid tumors with known microsatellite instability-high or mismatch repair deficient status, such as colorectal cancer or pancreatic cancer
- Participants with previously treated brain metastasis (es) that were asymptomatic or radiographically/clinically stable and not requiring steroids medications for 4 weeks prior to enrollment were permitted.
- Participants must have had archival tumor tissues or agreed to a tumor biopsy for analysis of predictive biomarkers such as programmed death-ligand 1 (PD-L1). (Fresh tumor biopsies were strongly recommended at baseline for biomarker analysis in participants with readily accessible tumor lesions and who consented to the biopsies).
- Participants must have had measurable disease as defined per Response Evaluation Criteria in Solid Tumor Version 1.1.
- Eastern Cooperative Oncology Group performance status of ≤ 1.
- Participants must have had adequate organ function as indicated by the following laboratory values:
- Absolute neutrophil count ≥ 1,500 /microliter
- Platelets ≥ 100,000 / milliliter (mL)
- Hemoglobin ≥ 9 grams/deciliter or ≥ 5.6 millimoles/liter
- Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
- Serum total bilirubin ≤ 1.5 X ULN
- Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 X ULN or ≤ 5 X ULN for participants with liver metastases
- International normalized ratio or prothrombin time ≤ 1.5 X ULN
- Activated partial thromboplastin time ≤ 1.5 X ULN
Key Exclusion Criteria
- History of severe hypersensitivity reactions to other Monoclonal antibodies.
- Prior malignancy active within the previous 2 years except for tumor for which a participant was enrolled in the study, and locally curable cancers that had been apparently cured, 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.
- Participants who failed to meet enrollment criteria for other PD-1 or PD-L1 trials solely due to low or negative predictive biomarkers.
- Participants with active autoimmune diseases or history of autoimmune diseases should have been excluded.
- Participants should have been excluded if they had a condition requiring systemic treatment with either corticosteroids (> 10 milligrams daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
- Had history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies.
- Known history of human immunodeficiency virus.
- Active infection requiring therapy, positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid except in participant with HCC, who met the following criteria:
- Hepatitis B virus (HBV) viral load < 200 international units/mL (approximately 1000 combined positive score/mL)
- Participants with active HBV infection needed
Data sourced from ClinicalTrials.gov (NCT02407990). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.