Advanced Pancreatic Cancer
Conditions
Keywords
CT-707, Focal Adhesion Kinase, Advanced Pancreatic Cancer
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
Detailed description
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.
Interventions
DRUGCT-707
Focal Adhesion Kinase (FAK) inhibitor
DRUGToripalimab
Programmed Death 1(PD-1) antibody
DRUGGemcitabine
nucleoside inhibitor
Sponsors
Shouyao Holdings (Beijing) Co. LTD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
* Patients must not enroll in this study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended phase 2 dose (RP2D) of CT-707 in combination with toripalimab and gemcitabine | Up to 24 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | Up to 24 months | Characterization of the safety and tolerability as determined by changes in laboratory values and electrocardiograms |
| Pharmacokinetics (Cmax) for CT-707 | Cycle 1 (each cycle is 21 days) | Defined as maximum observed plasma concentration |
| Pharmacokinetics (Tmax) for CT-707 | Cycle 1 (each cycle is 21 days) | Defined as time to maximum plasma concentration |
| Pharmacokinetics (AUC0-t) for CT-707 | Cycle 1 (each cycle is 21 days) | Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration |
| Overall response rate (ORR) as assessed by RECIST 1.1 criteria | Up to 24 months | Preliminary measure of anti-tumor activity of CT-707 in combination with toripalimab and gemcitabine |
| Progression free survival (PFS) according to RECIST v1.1 criteria | Up to 24 months | Preliminary measure of anti-tumor activity of CT-707 in combination with toripalimab and gemcitabine |
| Disease control rate (DCR) according to RECIST v1.1 | Up to 24 months | Preliminary measure of anti-tumor activity of CT-707 in combination with toripalimab and gemcitabine |
| Pharmacokinetics (t½) for CT-707 | Cycle 1 (each cycle is 21 days) | Defined as the apparent plasma terminal phase disposition half-life |
Other
| Measure | Time frame | Description |
|---|---|---|
| Predictive biomarkers for response to the combination of CT-707, toripalimab and gemcitabine | Up to 24 months | To assess putative predictive biomarkers such as PD-L1 and p-FAK |
Countries
China
Contacts
Primary ContactYinghui Sun, PhD
Outcome results
None listed