Clinical trial NCT06220318: Assessment of the Safety and Efficacy of C019199 Plus Sintilimab in Participants With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Lead sponsor: Fujian Haixi Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-01-23
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: DRUG: C019199

The C019199 will be taken orally, once a day

DRUG: Sintilimab

Sintilimab will be administrated with intravenous infusion, 200mg, every 3 weeks.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Age ≥18 years and \<76 years at the time of signing informed consent, male or female;
2. 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;
3. ECOG score: 0-1;
4. Life expectancy of 3 months or more;
5. Phase II: have measurable disease based on RECIST 1.1 ;
6. Phase II: agree to provide archival tumor tissue or newly obtained biopsy of a tumor lesion ;
7. Have adequate organ function ;
8. 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 ;
9. 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:

1. Known hypersensitivity to CSF-1R inhibitors or Sintilimab;
2. Receipt of (or planned receipt of) anti-tumor therapies within 4 weeks prior to first dose through the end of the study treatment period;
3. 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);
4. 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);
5. Major surgery (grade III or IV surgery) within 4 weeks prior to first dose without complete recovery;
6. 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;
7. 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);
8. Known active infection of human immunodeficiency virus (HIV) or hepatitis C virus (HCV);
9. For hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive subjects, HBV DNA level above upper limit of reference range;
10. Pregnant or lactating women;
11. Severe psychological or psychiatric abnormalities that may affect compliance with study requirements;
12. Detection of active or untreated CNS metastases on baseline imaging assessments by CT or MRI during screening: a) If new asymptomatic CNS metastases are detected on baseline scans, subjects must receive radiotherapy and/or surgery for CNS metastases, and can be enrolled without repeat CNS imaging if meeting all other criteria; b) Subjects with history of treated brain or meningeal metastases can be enrolled if clinically stable for at least 2 months and systemic high-dose corticosteroids (\>10 mg/day prednisone or equivalent) has been discontinued for at least 4 weeks.

Primary outcomes:
measure: Dose-Limiting Toxicity (DLT)
timeFrame: Cycle 1 (Cycle length=21 days)
measure: Objective Response Rate (ORR) Based on iRECIST
timeFrame: From date of enrollment until the date of first documented progression or death
measure: Progression-free Survival (PFS) after administration
timeFrame: From date of enrollment until the date of first documented progression or death
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events( TEAEs )and Serious Adverse Events （SAEs）
timeFrame: From the first dose until 28 days after the last dose
measure: Cmax
timeFrame: Cycle 1 Day 1; Cycle 1 Day 21
measure: AUC(0-t):
timeFrame: Cycle 1 Day 1; Cycle 1 Day 21
measure: T1/2
timeFrame: Cycle 1 Day 1; Cycle 1 Day 21
measure: Disease Control Rate (DCR) after administration
timeFrame: From date of enrollment until the date of first documented progression or death
measure: Duration of Remission (DoR) after administration
timeFrame: From date of enrollment until the date of first documented progression or death
measure: Overall Survival (OS) after administration
timeFrame: The time from the date of enrollment until death
Other outcomes:
Locations:
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
Study officials:
affiliation: The First Affiliated Hospital of Xiamen University
name: FENG YE
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunan Cancer Hospital
name: YONGCHANG ZHANG
role: PRINCIPAL_INVESTIGATOR
References: