Safety, Pharmacokinetics and Efficacy of CT-707, Toripalimab and Gemcitabine in Advanced Pancreatic Cancer

NCT ID: NCT05580445

Last Updated: 2023-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-11

Study Completion Date

2024-08-11

Brief Summary

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This study will assess the safety, tolerability, pharmacokinetics and antineoplastic activity of CT-707 in combination with toripalimab and gemcitabine in patients with advanced pancreatic cancer

Detailed Description

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This is a phase Ib/II, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics and antineoplastic activity of CT-707 in combination with toripalimab and gemcitabine in patients with advanced pancreatic cancer.The study consists of two parts, dose-escalation part and dose-expansion part. Both parts will enroll patients with advanced pancreatic cancer. Dose-escalation study is designed to determine the dose-limiting toxicity (DLTs) and recommended phase II dose (RP2D), and to characterize the safety, tolerability, and pharmacokinetics (PK) profile of CT-707 in combination with toripalimab and gemcitabine. Dose-expansion study phase is designed to evaluate the antitumor activity (objective response rate, progression-free survival, overall survival) of CT-707 in combination with toripalimab and gemcitabine in patients with advanced pancreatic cancer.

Conditions

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Advanced Pancreatic Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose-escalation and dose-expansion

Dose-escalation study is designed to determine the dose-limiting toxicity (DLTs) and recommended phase II dose (RP2D). Dose-expansion study is designed to evaluate the antitumor activity of CT-707 in combination with toripalimab and gemcitabine in patients with advanced pancreatic cancer.

Group Type EXPERIMENTAL

CT-707

Intervention Type DRUG

Focal Adhesion Kinase (FAK) inhibitor

Toripalimab

Intervention Type DRUG

Programmed Death 1(PD-1) antibody

Gemcitabine

Intervention Type DRUG

nucleoside inhibitor

Interventions

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CT-707

Focal Adhesion Kinase (FAK) inhibitor

Intervention Type DRUG

Toripalimab

Programmed Death 1(PD-1) antibody

Intervention Type DRUG

Gemcitabine

nucleoside inhibitor

Intervention Type DRUG

Other Intervention Names

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CT-707 granules Toripalimab injection GEMZAR

Eligibility Criteria

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Inclusion Criteria

* For inclusion in this study, patients must fulfil the following criteria:

1. Male or female (age of 18\~75 years old).
2. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
3. Patients must have a life expectancy of ≥ 3 months.
4. Patients must have histologically or cytologically confirmed advanced pancreatic adenocarcinoma or poorly differentiated pancreatic carcinoma that is metastatic to distant sites.
5. Patients are required to have measurable disease (RECIST v1.1), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10 mm with spiral CT scan.
6. Patients must have adequate organ and marrow function as defined below:

Blood routine: Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L; Platelet count (PLT) ≥ 100×10\^9/L; Hemoglobin (HGB) ≥ 90 g/L.

Liver function: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN), total bilirubin (TBIL) ≤ 1.5 times ULN in patients without liver metastases; AST and ALT ≤ 5 times ULN, TBIL ≤3 times ULN in patients with liver metastases.

Renal function: Serum creatinine (Scr) ≤1.5 times ULN or creatinine clearance ≥60 mL/min/1.73 m2.

Coagulation function: Activated partial thromboplastin time (APTT) ≤ 1.5 times ULN; International Normalized ratio (INR) ≤ 1.5 times ULN.
7. Patients must have recovered from any acute adverse events (except alopecia and peripheral neurotoxicity ≤ Grade 2).
8. Patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial and for 6 months after the trial; female participants must have a negative serum pregnancy test within 7 days prior to treatment.

Exclusion Criteria

1. Patients who have received chemotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor therapy within 4 weeks prior to the first use of the study drug.
2. Patients who have received clinical investigational drug or treatment within 4 weeks prior to the first use of the study drug.
3. Patients who have received major surgery within 4 weeks or had minor surgery within 2 weeks before the first dose of administration.
4. Patients who have previously received FAK inhibitor or programmed cell death protein 1/programmed cell death ligand 1 (PD-1/L1) antibody and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody are not eligible.
5. Patients receiving any medications or substances that are known to be moderate to strong inhibitors or inducers of CYP3A4 and which cannot be discontinued at least 1 week prior to the first dose of administration .
6. Patients who have active central nervous system (CNS)or leptomeningeal metastasis. However, participants who are asymptomatic, clinically stable, and did not require steroid therapy at least 4 weeks before the first dose of study treatment are eligible.
7. Patients who have cardiovascular and cerebrovascular diseases currently or within the last 6 months, including but not limited to:

I. Myocardial infarction; II. Unstable Angina pectoris; III. Cerebrovascular accident; IV. Other acute uncontrolled heart disease; Mean resting corrected QTc interval using the Fridericia formula (QTcF) \> 470 msec/female and \> 450 msec/male; Severe arrhythmias or abnormal cardiac conduction, such as ventricular arrhythmias requiring clinical intervention, degree ii-iii atrioventricular block, etc; Various factors that may increase the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, a family history of a first-degree relative with long QT syndrome or sudden unexplained death before the age of 40, receiving any medication with known QT prolongation; Left ventricular ejection fraction (LVEF) \< 40 % within 4 weeks prior to the first use of the study drug; Hypertension remains uncontrolled after aggressive antihypertensive therapy. Uncontrolled hypertension was defined as systolic blood pressure \> 185 mmHg and/or diastolic blood pressure \> 110 mmHg measured on 3 repetitions at least 10 minutes apart.
8. Patients suffering from conditions which are likely to adversely affect gastrointestinal motility (ulcerative disease, uncontrollable nausea, vomiting, diarrhea, or poor absorption syndrome).
9. Any evidence of severe or uncontrolled systemic disease, active infection or active bleeding diatheses, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
10. Patients have uncontrolled pleural, pericardial or abdominal effusion requiring drainage excluding those staying stable for at least two weeks after drainage.
11. Patients have active autoimmune disease that requires systemic treatment (immunomodulatory drugs, corticosteroids, or immunomodulatory drugs) in the past 2 years.
12. Patients with severely impaired lung functions such as pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia and drug-associated pneumonia.
13. Patients have allergic reactions to any component of CT-707, toripalimab and gemcitabine, or with history of severe allergic reactions to other monoclonal antibodies or gemcitabine.
14. Female patients who are pregnant or breast-feeding, or male or female patients of reproductive potential who are not employing an effective method of birth control.
15. Patients with mental disorder, alcohol and/or drug dependence.
16. The investigator considers that the subject has a history of serious systemic diseases or other reasons and is not suitable or not willing to participate in this clinical study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shouyao Holdings (Beijing) Co. LTD

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yinghui Sun, PhD

Role: STUDY_DIRECTOR

Shouyao Holdings (Beijing) Co. LTD

Locations

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Fudan University Shanghai Cancer Center

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Yinghui Sun, PhD

Role: CONTACT

86-10-88858616

Facility Contacts

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Xianjun Yu, PhD

Role: primary

13801669875

Other Identifiers

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CT-707-1

Identifier Type: -

Identifier Source: org_study_id