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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02492789




Registration number
NCT02492789
Ethics application status
Date submitted
26/06/2015
Date registered
9/07/2015
Date last updated
30/09/2019

Titles & IDs
Public title
A Trial to Evaluate Safety and Tolerability of INCSHR01210 in Cancer Patients
Scientific title
An Open-Label, Multicenter, Nonrandomized, Dose-Escalation and Tumor-Expansion Phase 1 Study to Evaluate the Safety and Tolerability of INCSHR01210 (Formerly SHR-1210) in Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
INCSHR1210-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors and Hematologic Malignancy 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - INCSHR01210 injection

Experimental: INCSHR01210 - 3 dose levels are designed in this study.3 to 6 patients (traditional "3+3" design) will be enrolled in each dose cohort. INCSHR01210 injection at each dose level is administered every 2 weeks (q2w, except in the first cycle).


Other interventions: INCSHR01210 injection
Part1: INCSHR01210 injection at a dose of 1, 3 or 10 mg/kg is administered every 2 weeks (3+3,q2w, except in the first cycle, in which subjects will be only dosed once on Day 1 for PK samplings and dose limiting toxicity observation). Response is assessed by every 2 cycles (4 weeks each cycle) by using irRECIST.
Part2: Additional patients (200mg dose cohorts will be enrolled in Part 2, depending on the data outcomes in Part 1, to further explore preliminarily clinical benefits of INCSHR01210 as well as the other objectives of the study.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Adverse Events as a Measure of Safety and Tolerability - Recommended phase II doses (RP2D) is 200 mg, and the only dose interval to be tested will be once every 4 weeks (Q4W).
Timepoint [1] 0 0
15 months
Secondary outcome [1] 0 0
Pharmacokinetics (PK) profile of INCSHR01210 (Tmax)
Timepoint [1] 0 0
Day 1 of cycle 1
Secondary outcome [2] 0 0
Maximum tolerated dose (MTD) of INCSHR01210
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Incidence of anti-INCSHR01210 antibody in serum
Timepoint [3] 0 0
15 months
Secondary outcome [4] 0 0
PD-1 receptor occupancy
Timepoint [4] 0 0
15 months
Secondary outcome [5] 0 0
Duration of response
Timepoint [5] 0 0
15 months
Secondary outcome [6] 0 0
Objective response rate
Timepoint [6] 0 0
15 months
Secondary outcome [7] 0 0
Time to progression
Timepoint [7] 0 0
15 months
Secondary outcome [8] 0 0
Pharmacokinetics (PK) profile of INCSHR01210 (Cmax)
Timepoint [8] 0 0
Day 1 of cycle 1
Secondary outcome [9] 0 0
Pharmacokinetics (PK) profile of INCSHR01210 (AUC0-28day)
Timepoint [9] 0 0
Day 28 of cycle 1
Secondary outcome [10] 0 0
Pharmacokinetics (PK) profile of INCSHR01210 (accumulation ratio R)
Timepoint [10] 0 0
Day 28 of each cycle

Eligibility
Key inclusion criteria
- Male or female at least 18 years of age;

- Patients diagnosed with solid tumors histologically or cytologically and documented as
advanced or metastatic disease for which there is no known effective anti-tumour
treatment (refractory to or relapsed from standard therapies);

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;

- Life expectancy = 12 weeks;

- Patients enrolled to Part 2 Expansion Cohorts:

- must have measurable lesion(s) according to the RECIST v1.1;

- Cohort A (endometrial carcinoma): Subjects diagnosed with histologically
confirmed advanced or metastatic endometrial carcinoma (sarcomas and mesenchymal
tumors are excluded). Subjects must have relapsed or be refractory to at least 1
prior standard therapy in the metastatic setting, have been intolerant to
standard therapies, or have refused standard therapy. In addition, subjects with
disease recurrence within 12 months of completion of adjuvant therapy are
eligible.

- Cohort B (thymic carcinoma): Subjects diagnosed with histologically or
cytologically confirmed advanced or metastatic thymic carcinoma based on local
guidelines.

- Cohort C (biliary tract carcinoma): Subjects diagnosed with histologically or
cytologically confirmed, advanced or metastatic extrahepatic cholangiocarcinoma
(carcinoma of the gallbladder or biliary tree) or carcinoma of the ampulla of
Vater. Subjects must have relapsed or be refractory to at least 1 prior standard
therapy, have been intolerant to standard therapies, or have refused standard
therapy.

- Cohort D (CUP): Subjects diagnosed with CUP based on ESMO guidelines.

- Adequate laboratory parameters at screening period as evidenced by:

- Absolute neutrophil count = 1.5×109/L (1,500/mm3)

- Platelets =100×109/L (100,000/mm3)

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

- Albumin levels = 2.8 g/dL

- Total bilirubin = 1.5×ULN

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5×ULN; for
patients with liver metastases, ALT and AST = 5×ULNSerum creatinine = 1.5×ULNAble to
understand and sign an informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects who fulfill any of the following criteria at screening will be ineligible for
admission:

- Subjects with any active autoimmune disease or history of autoimmune disease, or
history of syndrome that requires systemic steroids or immunosuppressive medications,
including but not limited to the following: rheumatoid arthritis, pneumonitis, colitis
(inflammatory bowel disease), hepatitis, hypophysitis, nephritis, hyperthyroidism, and
hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy.
Subjects with the following conditions will not be excluded from this study: asthma
that requires intermittent use of bronchodilators, hypothyroidism stable on hormone
replacement, vitiligo, Graves' disease, or Hashimoto's disease. Additional exceptions
may be made with medical monitor approval.

- Known history of hypersensitivity to any components of the INCSHR01210 formulation.

- Concurrent medical condition requiring the use of immunosuppressive medications, or
immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10
mg/day prednisone or equivalent are prohibited within 2 weeks before study drug
administration. Note: corticosteroids used for the purpose of intravenous contrast
allergy prophylaxis are allowed.

- Active CNS metastases (indicated by clinical symptoms, cerebral edema, steroid
requirement, or progressive disease). Subjects with brain or meningeal metastases that
were previously treated must be clinically stable (magnetic resonance imaging at least
4 weeks apart do not show evidence of new or enlarging metastases) and have
discontinued immunosuppressive doses of systemic steroids (> 10 mg/day prednisone or
equivalent) for at least 2 weeks before study drug administration.

- Uncontrolled clinically significant medical condition, including but not limited to
the following: (1) congestive heart failure (New York Health Authority Class > 2), (2)
unstable angina, (3) myocardial infarction within the past 12 months, or (4)
clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring
treatment or intervention.

- Prior systemic chemotherapy (< 6 weeks if chemotherapy including nitrosoureas or
mitomycin), radiotherapy, immunotherapy, hormone therapy, surgery or target therapy
within 4 weeks before the study drug administration, or any unresolved adverse events
> CTCAE Grade 1 (with the exception of any stable chronic toxicities not expected to
resolve).

- 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).

- History of immunodeficiency including seropositivity for human immunodeficiency virus,
or other acquired or congenital immune-deficient disease.

- Any other medical (eg, pulmonary, metabolic, congenital, endocrinal or CNS disease),
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 would interfere with the interpretation of
the results.

- Investigational therapy administered within 4 weeks before the first dose of
INCSHR01210.

- Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of
reactivation based on institutional guidelines and tests. Testing may include the
following: HBV DNA, HCV RNA, hepatitis B surface antigen, or anti-hepatitis B core
antibody.

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)
VIC
Recruitment hospital [1] 0 0
Austin Hospital/Olivia Newton-John Cancer Research Institute - Heidelberg
Recruitment hospital [2] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [3] 0 0
Chris O'Brien Life House - Camperdown
Recruitment hospital [4] 0 0
Nucleus Network - Melbourne
Recruitment hospital [5] 0 0
Linear Clinical Research Limited - Nedlands
Recruitment postcode(s) [1] 0 0
- Heidelberg
Recruitment postcode(s) [2] 0 0
- Blacktown
Recruitment postcode(s) [3] 0 0
- Camperdown
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
- Nedlands

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

Ethics approval
Ethics application status

Summary
Brief summary
This is an open-label, multicenter, non-randomized, dose escalation and tumor-expansion phase
I trial to evaluate safety and tolerability of INCSHR01210 in patients with advanced solid
tumors. The trial will enroll subjects with advanced solid tumor who have failed current
standard anti-tumor therapies.
Trial website
https://clinicaltrials.gov/show/NCT02492789
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