A Trial to Evaluate Safety and Tolerability of SHR-1316 in Cancer Patients

NCT03133247 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: SHR1316-002
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (5)

• Adverse events (AEs)

  Incidence of treatment-related AEs

  Up to 3 weeks

• Laboratory parameters

  Incidence of clinically significant laboratory abnormalities

  Up to 3 weeks

• Vital sign values

  Incidence of clinically significant vital sign abnormalities

  Up to 3 weeks

• ECG values

  Incidence of clinically significant ECG abnormalities

  Up to 3 weeks

• Dose-limiting toxicities (DLTs)

  Number of participants with DLTs

  Up to 3 weeks

Secondary Outcomes (6)

• Tmax

  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)

• Cmax

  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)

• AUC

  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)

• t1/2

  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)

• Receptor occupancy

  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

Study Arms (1)

SHR-1316 dose-escalation

EXPERIMENTAL

SHR-1316 doses will be escalated sequentially in 5 cohorts.

Drug: SHR-1316

Interventions

SHR-1316 DRUG

PD-L1

Also known as: HTI-1088

SHR-1316 dose-escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, each subject must meet all of the following criteria:
• Male or female ≥18 years of age;
• 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;
• Failed no more than 1 prior PD-1/PD-L1 therapy and that more than 4 weeks has elapsed.
• No prior cancer therapy within last 4 weeks;
• ECOG Performance Status of 0 or 1 at both the screening and baseline visits;
• Life expectancy ≥12 weeks;
• 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)

You may not qualify if:

• Subjects who fulfill any of the following criteria at screening will be ineligible to participate in this study:
• Known history of hypersensitivity to any components of the SHR-1316 product;
• 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;
• 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.
• 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;
• 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;
• 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).
• 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 (HIV), or other acquired or congenital immune-deficient disease, or any active systemic viral infection requiring therapy (e.g., hepatitis B or C);
• 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.

Sponsors & Collaborators

• Atridia Pty Ltd.: lead

Study Sites (1)

Linear Clinical Research

Perth, Western Australia, Australia

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2017
• First Posted: April 28, 2017
• Study Start: June 1, 2017
• Primary Completion: April 9, 2019
• Study Completion: July 5, 2019
• Last Updated: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)