A Phase I/II Clinical Study on the Safety, Tolerability and Preliminary Efficacy of C019199 in Combination With Sintilimab in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- C019199
- Conditions
- Solid Tumor
- Sponsor
- Fujian Haixi Pharmaceuticals Co., Ltd.
- Enrollment
- 155
- Locations
- 2
- Primary Endpoint
- Progression-free Survival (PFS) after administration
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
This is a phase I/II non-randomized, open-label, single-arm, multicenter study to evaluate the Safety and Efficacy of C019199 Plus Sintilimab in Participants With Advanced Solid Tumors.
Detailed Description
Phase I will determine and confirm the maximum tolerated dose(MTD) and recommended phase II dose(RP2D) for C019199 in combination with 200 milligrams (mg) ( intravenous\[IV\], every 3 weeks \[Q3W\]) Sintilimab in patients with advanced Solid tumors. Phase II will evaluate the safety and efficacy of the combination of C019199 and Sintilimab in selected solid tumors at the RP2D from Phase I.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •Age ≥18 years and \<76 years at the time of signing informed consent, male or female;
- •Histologically or cytologically confirmed locally advanced or metastatic solid tumors that have progressed on or intolerant to standard therapy or whom no standard therapy exists;
- •ECOG score: 0-1;
- •Life expectancy of 3 months or more;
- •Phase II: have measurable disease based on RECIST 1.1 ;
- •Phase II: agree to provide archival tumor tissue or newly obtained biopsy of a tumor lesion ;
- •Have adequate organ function ;
- •A male or female participant must agree to use contraception during the treatment period and for at least 6 months after the last dose of study treatment ;
- •Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
Exclusion Criteria
- •Subjects meeting any of the following criteria must be excluded from this study:
- •Known hypersensitivity to CSF-1R inhibitors or Sintilimab;
- •Receipt of (or planned receipt of) anti-tumor therapies within 4 weeks prior to first dose through the end of the study treatment period;
- •Incomplete recovery from prior therapy toxicities (i.e. grade 2 or higher toxicities at screening, except for alopecia, pigmentation changes, or immune-mediated hypothyroidism that is stable with hormone replacement);
- •History of malignancies other than the cancer being treated in this study (Exceptions include: malignancies that have been cured with no recurrence within 3 years prior to enrollment; completely resected basal cell or squamous cell skin cancer; any completely resected carcinoma in situ);
- •Major surgery (grade III or IV surgery) within 4 weeks prior to first dose without complete recovery;
- •History of prior surgeries or severe gastrointestinal diseases such as dysphagia, active gastric ulcers, ulcerative colitis, Crohn's disease, intestinal obstruction etc., that may affect absorption, distribution, metabolism of study treatment per investigator's judgement;
- •Any significant clinical or laboratory abnormalities that are considered clinically significant per investigator's judgement and make the subject unsuitable for enrollment, such as: uncontrolled active infections (CTCAE v5.0 grade 2), uncontrolled diabetes (fasting blood glucose \>7.8 mmol/L despite optimal medical therapy), uncontrolled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg despite optimal medical therapy), peripheral neuropathy ≥ grade 2 (CTCAE v5.0), congestive heart failure ≥ grade 2 (CTCAE v5.0), myocardial infarction within the last 6 months, severe/unstable angina or coronary/peripheral artery bypass graft, arterial thromboembolism or deep vein thrombosis, stroke and/or transient ischemic attack, moderate to severe hepatic cirrhosis, uncontrolled major seizure disorders, known history of autoimmune disease that is active or may relapse (except for clinically stable hypothyroidism);
- •Known active infection of human immunodeficiency virus (HIV) or hepatitis C virus (HCV);
- •For hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive subjects, HBV DNA level above upper limit of reference range;
Arms & Interventions
C019199 plus Sintilimab
Patients with selected tumors will received oral C019199 at a starting dose of 100mg once daily in combination with intravenous Sintilimab 200mg every 3 weeks ( Q3W ) on a 21-day treatment cycle until disease progression, development of unacceptable toxicity, or withdrawal of consent .
Intervention: C019199
C019199 plus Sintilimab
Patients with selected tumors will received oral C019199 at a starting dose of 100mg once daily in combination with intravenous Sintilimab 200mg every 3 weeks ( Q3W ) on a 21-day treatment cycle until disease progression, development of unacceptable toxicity, or withdrawal of consent .
Intervention: Sintilimab
Outcomes
Primary Outcomes
Progression-free Survival (PFS) after administration
Time Frame: From date of enrollment until the date of first documented progression or death
Progression-free Survival (PFS) is defined as the time from the date of first dose of the study drug to the first documented disease progression (according to iRECIST ) or death (due to any cause), whichever occurs first.
Dose-Limiting Toxicity (DLT)
Time Frame: Cycle 1 (Cycle length=21 days)
Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose.
Objective Response Rate (ORR) Based on iRECIST
Time Frame: From date of enrollment until the date of first documented progression or death
ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) for target and non-target lesions.
Secondary Outcomes
- T1/2(Cycle 1 Day 1; Cycle 1 Day 21)
- Overall Survival (OS) after administration(The time from the date of enrollment until death)
- Number of Participants With Treatment-emergent Adverse Events( TEAEs )and Serious Adverse Events （SAEs）(From the first dose until 28 days after the last dose)
- Cmax(Cycle 1 Day 1; Cycle 1 Day 21)
- Duration of Remission (DoR) after administration(From date of enrollment until the date of first documented progression or death)
- AUC(0-t):(Cycle 1 Day 1; Cycle 1 Day 21)
- Disease Control Rate (DCR) after administration(From date of enrollment until the date of first documented progression or death)