COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted/resubmitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04215978




Registration number
NCT04215978
Ethics application status
Date submitted
30/12/2019
Date registered
2/01/2020
Date last updated
9/03/2020

Titles & IDs
Public title
Safety and Preliminary Effectiveness of BGB-A445 in Combination With Tislelizumab in Participants With Advanced Solid Tumors
Scientific title
Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of the Anti OX40 Agonist Monoclonal Antibody BGB-A445 in Combination With the Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors
Secondary ID [1] 0 0
BGB-A317-A445-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BGB-A445
Treatment: Drugs - tislelizumab

Experimental: Phase 1a: BGB-A445 Monotherapy - Dose Escalation Part A: Participants will receive intravenous (IV) infusion of BGB-A445 in sequential cohorts of approximately 5 increasing dose levels on day 1 of each 21-day cycle

Experimental: Phase 1a: BGB-A445 + Tislelizumab Combination Therapy - Dose Escalation Part B: Participants will receive IV infusion of BGB-A445 in sequential cohorts of approximately 3 increasing dose levels plus 200mg tislelizumab on day 1 of each 21-day cycle

Experimental: Phase 1b:BGB-A445 Monotherapy or Combination with Tislelizumab - Dose Expansion: Participants will receive recommended Phase 2 doses (RP2D(s)) of IV BGB-A445 alone or in combination with tislelizumab as determined from Phase 1a Dose Escalation


Treatment: Drugs: BGB-A445
Administered as specified in the treatment arm

Treatment: Drugs: tislelizumab
Administered as specified in the treatment arm

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1a: Number of Participants Experiencing Adverse Events (AEs)
Timepoint [1] 0 0
Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Primary outcome [2] 0 0
Phase 1a: Number of Participants Experiencing Serious Adverse Events (SAEs)
Timepoint [2] 0 0
Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Primary outcome [3] 0 0
Phase 1a: number of Participants Experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria
Timepoint [3] 0 0
Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Primary outcome [4] 0 0
Phase 1a: Maximum Tolerated Dose (MTD) of BGB-A445 - The MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 30%
Timepoint [4] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Primary outcome [5] 0 0
Maximum RP2D of BGB-A445 when Administered Alone
Timepoint [5] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Primary outcome [6] 0 0
Maximum RP2D of BGB-A445 when Administered in Combination with Tislelizumab
Timepoint [6] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Primary outcome [7] 0 0
Overall Response Rate (ORR) as Assessed by the Investigator - ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)
Timepoint [7] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary outcome [1] 0 0
Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator
Timepoint [1] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary outcome [2] 0 0
Phase 1a: Duration of Response (DOR) as Assessed by the Investigator
Timepoint [2] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary outcome [3] 0 0
Phase 1a: Disease-Control Rate (DCR) as Assessed by the Investigator
Timepoint [3] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary outcome [4] 0 0
Phase 1a: Serum Concentration of BGB-A445
Timepoint [4] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [5] 0 0
Phase 1a: Serum Concentration of tislelizumab
Timepoint [5] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [6] 0 0
Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-A445
Timepoint [6] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [7] 0 0
Phase 1a: Maximum Observed Plasma Concentration (Cmax) of tislelizumab
Timepoint [7] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [8] 0 0
Phase 1a: Minimum Observed Plasma Concentration (Cmin) of BGB-A445
Timepoint [8] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [9] 0 0
Phase 1a: Minimum Observed Plasma Concentration (Cmin) of tislelizumab
Timepoint [9] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [10] 0 0
Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-A445
Timepoint [10] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [11] 0 0
Phase 1a: Time to Maximum Plasma Concentration (Tmax) of tislelizumab
Timepoint [11] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [12] 0 0
Phase 1a: Area Under the Concentration-Time Curve of 0-21 Days (AUC0-21d) of BGB-A445
Timepoint [12] 0 0
60 minutes predose up to 21 days postdose
Secondary outcome [13] 0 0
Phase 1a: Immunogenic Responses to BGB-A445 as assessed through the detection of antidrug antibodies
Timepoint [13] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary outcome [14] 0 0
Phase 1a: Immunogenic Responses to tislelizumab as assessed through the detection of antidrug antibodies
Timepoint [14] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary outcome [15] 0 0
Phase 1b: Progression-free survival (PFS) as Assessed by the Investigator - Determined from investigator derived tumor assessments as per RECIST 1.1
Timepoint [15] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary outcome [16] 0 0
Phase 1b: Duration of Response (DOR) as Assessed by the Investigator
Timepoint [16] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary outcome [17] 0 0
Phase 1b: Disease-Control Rate (DCR) as Assessed by the Investigator
Timepoint [17] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary outcome [18] 0 0
Phase 1b: Number of Participants Experiencing Adverse Events (AEs)
Timepoint [18] 0 0
Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Secondary outcome [19] 0 0
Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs)
Timepoint [19] 0 0
Up to 90 days after the last dose of study drug(s) regardless of whether the participant starts a subsequent anticancer therapy
Secondary outcome [20] 0 0
Phase 1b: Serum Concentration of BGB-A445
Timepoint [20] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [21] 0 0
Phase 1b: Serum Concentration of tislelizumab
Timepoint [21] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [22] 0 0
Phase 1b: Maximum Observed Plasma Concentration (Cmax) of BGB-A445
Timepoint [22] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [23] 0 0
Phase 1b: Maximum Observed Plasma Concentration (Cmax) of tislelizumab
Timepoint [23] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [24] 0 0
Phase 1b: Minimum Observed Plasma Concentration (Cmin) of BGB-A445
Timepoint [24] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [25] 0 0
Phase 1b: Minimum Observed Plasma Concentration (Cmin) of tislelizumab
Timepoint [25] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [26] 0 0
Phase 1b: Time to Maximum Plasma Concentration (Tmax) of BGB-A445
Timepoint [26] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [27] 0 0
Phase 1b: Time to Maximum Plasma Concentration (Tmax) of tislelizumab
Timepoint [27] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [28] 0 0
Phase 1b: Area Under the Concentration-Time Curve of 0-21 Days (AUC0-21d) of BGB-A445
Timepoint [28] 0 0
60 minutes predose up to 21 days postdose
Secondary outcome [29] 0 0
Phase 1b: Immunogenic Responses to BGB-A445 as assessed through the detection of antidrug antibodies
Timepoint [29] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first
Secondary outcome [30] 0 0
Phase 1b: Immunogenic Responses to tislelizumab as assessed through the detection of antidrug antibodies
Timepoint [30] 0 0
Up to 30 days after the last dose of study drug(s) or before the initiation of a new anticancer treatment, whichever occurs first

Eligibility
Key inclusion criteria
Key

1. Phase 1a (dose escalation): Participants with histologically or cytologically
confirmed advanced, metastatic, unresectable solid tumors who have previously received
standard systemic therapy or for whom treatment is not available, not tolerated or
refused.

1. Enrollment will be limited to participants with advanced solid tumors for which
there is clinical evidence of response to T cell based immuno-oncology agents
(eg, anti PD 1) or other scientific evidence in support of an immunologically
sensitive tumor type.

2. Participant has not received prior therapy targeting OX40 or any other T cell
agonist therapy (prior checkpoint inhibitor therapy is allowed)

2. Has at least 1 measurable lesion as defined per RECIST 1.1. The target lesion(s)
selected have not been previously treated with local therapy OR the target lesion(s)
selected that are within the field of prior local therapy have subsequently progressed
as defined by RECIST 1.1

3. Participants must be able to provide an archived formalin fixed paraffin embedded
(FFPE) tumor tissue sample (block or approximately 15 freshly unstained FFPE slides)
after the most recent line of therapy. If archival tissue is not available, fresh
tumor biopsy is mandatory.

a. Participants enrolled must provide baseline tumor tissue as outlined as well as be
willing and medically fit to undergo mandatory on treatment biopsies with no excessive
risk as judged by the investigator

4. Eastern Cooperative Oncology Group (ECOG) Performance Status = 1

5. Adequate organ function as indicated by the following laboratory values up to first
dose of study drug

1. Participants must not have required blood transfusion or growth factor support =
14 days before sample collection for the following:

- Absolute neutrophil count = 1.5 x 109/L

- Platelet count = 75 x 109/L

- Hemoglobin = 90g/L

2. Serum creatinine =1.5 x upper limit of normal (ULN) or estimated glomerular
filtration rate (GFR) = 60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) equation

- The estimated GFR for participants with renal cell carcinoma must be = 30
mL/min/1.73 m2 by the CKD-EPI equation

3. Serum total bilirubin = 1.5 x ULN (< 3 x ULN for participants with Gilbert
syndrome)

4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 x ULN;

- = 5 x ULN for participants with hepatocellular carcinoma or liver metastases

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Active leptomeningeal disease or uncontrolled brain metastasis. Participants with
equivocal findings or with confirmed brain metastases are eligible for enrollment
provided they are asymptomatic and radiologically stable without the need for
corticosteroid treatment for at least 4 weeks prior to the first dose of study drug(s)

2. Active autoimmune diseases or history of autoimmune diseases that may relapse or
history of life-threatening toxicity related to prior immune therapy, with the
following exceptions:

1. Controlled type 1 diabetes

2. Hypothyroidism (provided it is managed with hormone-replacement therapy only)

3. Controlled celiac disease

4. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or
alopecia)

5. Any other disease that is not expected to recur in the absence of external
triggering factors (requires consultation with the medical monitor prior to
enrollment)

3. Any active malignancy = 2 years before the first dose of study drug(s) except for the
specific cancer under investigation in this study and any locally recurring cancer
that has been treated with curative intent (eg, resected basal or squamous cell skin
cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast)

4. Any condition that required systemic treatment with either corticosteroids (> 10 mg
daily of prednisone or equivalent) or other immunosuppressive medication = 14 days
before the first dose of study drug(s), with the following exceptions:

1. Adrenal replacement steroid (dose = 10 mg daily of prednisone or equivalent)

2. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with
minimal systemic absorption

3. Short course (= 7 days) of corticosteroid prescribed prophylactically (eg, for
contrast dye allergy) or for the treatment of a nonautoimmune condition (eg,
delayed-type hypersensitivity reaction caused by contact allergen)

5. Any of the following cardiovascular risk factors:

1. Cardiac chest pain, defined as moderate pain that limits instrumental activities
of daily living, = 28 days before the first dose of study drug(s)

2. Pulmonary embolism = 28 days before the first dose of study drug(s)

3. Any history of acute myocardial infarction = 6 months before the first dose of
study drug(s)

4. Heart failure that meets the New York Heart Association Classification III or IV
= 6 months before the first dose of study drug(s)

5. Any event of ventricular arrhythmia = Grade 2 in severity = 6 months before the
first dose of study drug(s)

6. Any history of cerebrovascular accident = 6 months before the first dose of study
drug(s)

7. Uncontrolled hypertension: systolic pressure = 140 mmHg or diastolic pressure =
90 mmHg on repeated measurements that cannot be managed by standard
antihypertension medications = 28 days before the first dose of study drug(s)

8. Any episode of syncope or seizure = 28 days before the first dose of study
drug(s)

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Nucleus Network - Melbourne
Recruitment hospital [2] 0 0
Linear Clinical Research - Perth
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
6009 - Perth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BeiGene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the safety and tolerability of BGB-A445 alone and in
combination with tislelizumab in participants with advanced solid tumors; and to determine
the maximum tolerated dose(s) (MTD) or maximum administered dose(s) (MAD) and recommended
Phase 2 doses (RP2D) of BGB-A445 alone and in combination with tislelizumab.
Trial website
https://clinicaltrials.gov/show/NCT04215978
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Brandon Beagle, PhD
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BeiGene
Address 0 0
Country 0 0
Phone 0 0
1-877-828-5568
Fax 0 0
Email 0 0
clinicaltrials@beigene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04215978