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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03133247




Registration number
NCT03133247
Ethics application status
Date submitted
8/04/2017
Date registered
28/04/2017
Date last updated
30/09/2019

Titles & IDs
Public title
A Trial to Evaluate Safety and Tolerability of SHR-1316 in Cancer Patients
Scientific title
A Phase 1, Open-Label, Multicenter, Non-Randomized, Dose Escalation Study to Evaluate the Safety and Tolerability of SHR-1316 in Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
SHR1316-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SHR-1316

Experimental: SHR-1316 dose-escalation - SHR-1316 doses will be escalated sequentially in 5 cohorts.


Treatment: Drugs: SHR-1316
PD-L1

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

Outcomes
Primary outcome [1] 0 0
Adverse events (AEs) - Incidence of treatment-related AEs
Timepoint [1] 0 0
Up to 3 weeks
Primary outcome [2] 0 0
Laboratory parameters - Incidence of clinically significant laboratory abnormalities
Timepoint [2] 0 0
Up to 3 weeks
Primary outcome [3] 0 0
Vital sign values - Incidence of clinically significant vital sign abnormalities
Timepoint [3] 0 0
Up to 3 weeks
Primary outcome [4] 0 0
ECG values - Incidence of clinically significant ECG abnormalities
Timepoint [4] 0 0
Up to 3 weeks
Primary outcome [5] 0 0
Dose-limiting toxicities (DLTs) - Number of participants with DLTs
Timepoint [5] 0 0
Up to 3 weeks
Secondary outcome [1] 0 0
Tmax - Time to maximum plasma concentration
Timepoint [1] 0 0
Cycle 1 Day 1 (pre-dose and 5 min, 1 hr, 2 hr, and 6 hr post-dose), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22; Day 1 from Cycle 2 onwards (pre-dose and 5-min post-dose)
Secondary outcome [2] 0 0
Cmax - Maximum plasma drug concentration
Timepoint [2] 0 0
Cycle 1 Day 1 (pre-dose and 5 min, 1 hr, 2 hr, and 6 hr post-dose), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22; Day 1 from Cycle 2 onwards (pre-dose and 5-min post-dose)
Secondary outcome [3] 0 0
AUC - Area under the time-concentration curve
Timepoint [3] 0 0
Cycle 1 Day 1 (pre-dose and 5 min, 1 hr, 2 hr, and 6 hr post-dose), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22; Day 1 from Cycle 2 onwards (pre-dose and 5-min post-dose)
Secondary outcome [4] 0 0
t1/2 - Observed terminal half-life
Timepoint [4] 0 0
Cycle 1 Day 1 (pre-dose and 5 min, 1 hr, 2 hr, and 6 hr post-dose), Day 2, Day 3, Day 4, Day 8, Day 15, Day 22; Day 1 from Cycle 2 onwards (pre-dose and 5-min post-dose)
Secondary outcome [5] 0 0
Receptor occupancy - PD-1 receptor occupancy in blood
Timepoint [5] 0 0
Cycle 1 Day 1 (pre-dose, 1 hr post-dose); Cycle 1 Day 4; Cycle 1 Day 8; Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1
Secondary outcome [6] 0 0
Immunogenicity - Incidence of anti-SHR-1316 antibodies
Timepoint [6] 0 0
Cycle 1 Day 1 (pre-dose), Cycle 1 Day 8, Cycle 1 Day 15; pre-dose on Day 1 of Cycle 2 onwards

Eligibility
Key inclusion criteria
Inclusion Criteria

To be eligible to participate in this study, each subject must meet all of the following
criteria:

1. Male or female =18 years of age;

2. Diagnosed (histologically or cytologically) with solid tumors and documented as
advanced or metastatic disease for which there is no known effective anti-tumor
treatment (refractory to or relapsed from standard therapies). Subjects must have
confirmation of this diagnosis through study-site analysis of fresh or archived
tissue;

3. Failed no more than 1 prior PD-1/PD-L1 therapy and that more than 4 weeks has elapsed.

4. No prior cancer therapy within last 4 weeks;

5. ECOG Performance Status of 0 or 1 at both the screening and baseline visits;

6. Life expectancy =12 weeks;

7. Adequate laboratory parameters during screening as evidenced by:

- Absolute neutrophil count =1.5×109/L (1500/mm3)

- Platelets =100×109/L (100,000/mm3)

- Hemoglobin (Hgb) =9.0 g/dL (90 g/L)

- Albumin levels =2.8 g/dL

- Total bilirubin =1.5 times the upper limit of normal (× ULN)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5× ULN;
for subjects with liver metastases, ALT and AST =5× ULN

- Serum creatinine =1.5×ULN or creatinine clearance =50 mL/min (using
Cockcroft-Gault equation)

8. Female subjects agree not to be pregnant or lactating from beginning of the study
screening to 3 months after receiving the last treatment:

- Both men and women of reproductive potential are willing and able to employ a
highly effective method of birth control/contraception to prevent pregnancy

- A highly effective method of contraception is defined as one that results in a
low failure rate, i.e., less than 1% per year, when used consistently and
correctly

9. Willing and able to comply with clinic visits and study-related procedures;

10. Provide signed informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Subjects who fulfill any of the following criteria at screening will be ineligible to
participate in this study:

1. Known history of hypersensitivity to any components of the SHR-1316 product;

2. Any investigational or concurrent cancer therapy (including surgery, radiotherapy,
immunotherapy, hormone therapy, or target therapy), administered within 4 weeks or 5
half-lives, whichever is longer, before the first dose of SHR-1316; or within 6 weeks
in the case of certain therapies (e.g., extensive radiotherapy, major surgery,
mitomycin C and nitrosoureas). Any such, prior systemic therapy needs to be outside of
five half-lives, unless discussed and explained with the sponsor. Any AEs from prior
therapy must have returned to = Grade 1 CTCAE level;

3. Subjects with active, known, or suspected autoimmune disease. Subjects with vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, euthyroid patients with a history of Grave's disease
(subjects with suspected autoimmune thyroid disorders must be negative for
thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin
prior to first dose of study drug), psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted
to enroll.

4. Active central nervous system (CNS) metastases, as indicated by clinical symptoms,
cerebral edema, steroid requirement, or progressive disease. Prior treated brain or
meningeal metastases must be clinically stable (MRI) for at least 8 weeks and off
immunosuppressive doses of systemic steroids (<10 mg/day prednisone or equivalent) for
at least 4 weeks before study drug administration;

5. Clinically significant cardiovascular condition, including: (1) history of congestive
heart failure (NYHA Class >2), (2) history of unstable angina, (3) myocardial
infarction within the past 12 months, or (4) history of supraventricular arrhythmia or
ventricular arrhythmia requiring treatment or intervention;

6. History or presence of an abnormal ECG that, in the investigator's opinion, is
clinically meaningful:

• For example, a screening QTcF interval that is prolonged (>450 milliseconds [msec]
in males; >470 msec in females).

7. Active infection or an unexplained fever >38.5°C during screening visits or on the
first scheduled day of dosing (at the discretion of the investigator, subjects with
tumor fever may be enrolled);

8. History of immunodeficiency including seropositivity for human immunodeficiency virus
(HIV), or other acquired or congenital immune-deficient disease, or any active
systemic viral infection requiring therapy (e.g., hepatitis B or C);

9. Any other medical (e.g., pulmonary, metabolic, congenital, endocrinal or CNS disease,
etc.), psychiatric, or social condition deemed by the investigator to be likely to
interfere with a subject's rights, safety, welfare or ability to sign informed
consent, cooperate and participate in the study, or interfere with the interpretation
of the results.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)
West Australi
Recruitment hospital [1] 0 0
Linear Clinical Research - Perth
Recruitment postcode(s) [1] 0 0
- Perth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Atridia Pty Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
In many types of human tumors, PD-L1 is highly expressed. Such high expression has often been
associated with poor prognosis in cancer patients. SHR-1316 is a humanized IgG4 monoclonal
antibody that binds specifically to human PD-L1.
Trial website
https://clinicaltrials.gov/show/NCT03133247
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications