SHR-1701 in Metastatic or Locally Advanced Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase I, Open-label Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of SHR-1701 in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03710265
• Other study ID #: SHR-1701-I-101
• Status: Recruiting
• Phase: Phase 1
• Start date: November 20, 2018
• Est. completion date: December 31, 2022

Study information

• Verified date: November 2021
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: Linna Wang, MD
• Phone: +86-10-67166319
• Email: Linna.wang[@]hengrui.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this Phase I study is to access the safety and tolerability of SHR-1701 at different dose levels. It is hoped to find out the recommended dose for Phase II/III.

Description:

This is a Phase I, open-label trial in patients with metastatic or locally advanced solid tumor. There are three parts of the study: a dose-escalation part, a dose-expansion part, and a clinical expansion part. Dose escalation part is a standard "3+3" cohort design, for which 3 or 6 subjects will be enrolled at each dose level depending on the occurrence of dose-limiting toxicities (DLTs). Dose-expansion means that at least 10 subjects (included subjects of the dose-escalation part) will be selected in 2 - 3 dose levels to focus on the pharmacokinetics (PK) / pharmacodynamic (PD) features. After determination of the recommended dose for Phase II (RP2D), clinical expansion will be opened. Many more subjects will be invited to take part in the study and received the study drug at the RP2D. Additional purpose of the study is to find out whether the study drug has anti-tumor effects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 206
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or female subjects aged between 18 and 75 years

• Life expectancy >= 12 weeks as judged by the Investigator

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

• Has measurable disease per RECIST 1.1

• Subjects with confirmed metastatic or locally advanced solid tumor (histologically or cytologically) and there is no known effective anti-tumor treatment (refractory or relapsed from standard treatment).

• Adequate hematological, hepatic and renal function as defined in the protocol

• Females of childbearing potential (FOCBP), who are not surgically sterile or postmenopausal, must conduct pregnancy test (serum or urine) within 7 days before enrollment, and must not be pregnant or breast-feeding women. If the result is negative, she must agree to use adequate contraception during the experiment and 3 months after the last administration of the test drugs. And non-sterilized males who are sexually active must agree to use adequate contraception during the experiment and 3 months after the last administration of the test drugs.

• Able to understand and sign an informed consent, and able to comply with all procedures

Exclusion Criteria:

• Anticancer treatment within 28 days before the first dose of study drug

• Major surgery within 28 days before start of trial treatment (prior diagnostic biopsy is permitted)

• Systemic therapy with immunosuppressive agents within 7 days prior to the first dose of study drug; or use any investigational drug within 28 days before the start of trial treatment

• With any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded

• Subjects with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded

• Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure (New York heart association (NYHA) class > 2), or ventricular arrhythmia which need medical intervention.

• History of immunodeficiency including seropositive 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

• Previous malignant disease (other than the target malignancy to be investigated in the trial) within the last 2 years. Subjects with history of cervical carcinoma in situ, superficial or non-invasive bladder cancer or basal cell or squamous cell cancer in situ previously treated with curative intent are NOT excluded.

• Receipt of any organ transplantation, including allogeneic stem-cell transplantation

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• SHR-1701
Subjects will receive an intravenous infusion of SHR-1701 in a dose escalation until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability profile of SHR-1701	Number of Subjects who occurs dose-limiting toxicity (DLTs)	Up to week 3
Primary	Objective Response Rate (ORR) assessed by site investigator as per RECIST 1.1		Screening up to study completion, an average of 1 year
Secondary	Area under the plasma concentration versus time curve (AUC) of SHR-1701		Up to 4 weeks after last treatment
Secondary	Peak Plasma Concentration (Cmax) of SHR-1701		Up to 4 weeks after last treatment
Secondary	Half-time (t1/2) of SHR-1701		Up to 4 weeks after last treatment
Secondary	Pharmacodynamic features of SHR-1701	SHR-1701 receptor occupation	12 months (anticipated)
Secondary	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors	ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ¡Ý30% decrease in the sum of diameters of target lesions) per RECIST 1.1.	12 months (anticipated)
Secondary	Disease Control Rate (DCR) per RECIST 1.1	DCR is defined as the percentage of participants in the analysis population who have a CR, PR or SD per RECIST 1.1.	12 months (anticipated)
Secondary	Best Overall Response (BOR) per RECIST 1.1		12 months (anticipated)
Secondary	Immunogenicity of SHR-1701	anti SHR-1603 antibodies (ADA)	12 months (anticipated)
Secondary	Trough plasma concentration (C trough) of SHR-1701		Up to 4 weeks after last treatment
Secondary	Immunogenicity of SHR-1701		12 months (anticipated)
Secondary	Disease Control Rate (DCR) per RECIST 1.1		12 months (anticipated)
Secondary	Clinical Benefit Rate(CBR) per RECIST 1.1		12 months (anticipated)
Secondary	Progression-Free Survival (PFS) per RECIST 1.1		12 months (anticipated)
Secondary	Duration of Response (DoR) per RECIST 1.1		12 months (anticipated)
Secondary	Overall Survival (OS)		12 months (anticipated)