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

NCT05580445 | Unknown Phase 1

• 1 other identifier: CT-707-1
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Advanced Pancreatic Cancer

Keywords

CT-707, Focal Adhesion Kinase, Advanced Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose (RP2D) of CT-707 in combination with toripalimab and gemcitabine

  The RP2D will be determined from the maximum tolerated dose (MTD) found in the dose-escalation cohort. The MTD is determined as the dose at which no more than one patient (out of six) experiences any drug-related toxicity (DLT)

  Up to 24 months

Secondary Outcomes (8)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  Up to 24 months

• Pharmacokinetics (Cmax) for CT-707

  Cycle 1 (each cycle is 21 days)

• Pharmacokinetics (Tmax) for CT-707

  Cycle 1 (each cycle is 21 days)

• Pharmacokinetics (AUC0-t) for CT-707

  Cycle 1 (each cycle is 21 days)

• Pharmacokinetics (t½) for CT-707

  Cycle 1 (each cycle is 21 days)

Other Outcomes (1)

• Predictive biomarkers for response to the combination of CT-707, toripalimab and gemcitabine

  Up to 24 months

Study Arms (1)

Dose-escalation and dose-expansion

EXPERIMENTAL

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.

Drug: CT-707; Drug: Toripalimab; Drug: Gemcitabine

Interventions

CT-707 DRUG

Focal Adhesion Kinase (FAK) inhibitor

Also known as: CT-707 granules

Dose-escalation and dose-expansion

Toripalimab DRUG

Programmed Death 1(PD-1) antibody

Also known as: Toripalimab injection

Dose-escalation and dose-expansion

Gemcitabine DRUG

nucleoside inhibitor

Also known as: GEMZAR

Dose-escalation and dose-expansion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female (age of 18\~75 years old).
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients must have a life expectancy of ≥ 3 months.
• Patients must have histologically or cytologically confirmed advanced pancreatic adenocarcinoma or poorly differentiated pancreatic carcinoma that is metastatic to distant sites.
• 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.
• 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.
• Patients must have recovered from any acute adverse events (except alopecia and peripheral neurotoxicity ≤ Grade 2).
• 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.

You may not qualify if:

• 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.
• Patients who have received clinical investigational drug or treatment within 4 weeks prior to the first use of the study drug.
• Patients who have received major surgery within 4 weeks or had minor surgery within 2 weeks before the first dose of administration.
• 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.
• 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 .
• 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.
• 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.
• Patients suffering from conditions which are likely to adversely affect gastrointestinal motility (ulcerative disease, uncontrollable nausea, vomiting, diarrhea, or poor absorption syndrome).
• 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).
• Patients have uncontrolled pleural, pericardial or abdominal effusion requiring drainage excluding those staying stable for at least two weeks after drainage.
• Patients have active autoimmune disease that requires systemic treatment (immunomodulatory drugs, corticosteroids, or immunomodulatory drugs) in the past 2 years.
• Patients with severely impaired lung functions such as pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia and drug-associated pneumonia.
• 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.
• 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.

Sponsors & Collaborators

• Shouyao Holdings (Beijing) Co. LTD: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

RECRUITING

MeSH Terms

Interventions

conteltinib; toripalimab; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Yinghui Sun, PhD

  Shouyao Holdings (Beijing) Co. LTD

  STUDY DIRECTOR

Central Study Contacts

Yinghui Sun, PhD

CONTACT

86-10-88858616; yhsun@centaurusbio.com

Study Design

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

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: October 14, 2022
• Study Start: August 11, 2022
• Primary Completion: August 11, 2024
• Study Completion: August 11, 2024
• Last Updated: November 22, 2023

Record last verified: 2023-11

Locations

CN (1)