Assessment of the Safety and Efficacy of C019199 Plus Sintilimab in Participants With Advanced Solid Tumors

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06220318
• Other study ID #: HXP019-CTPI-02
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 19, 2023
• Est. completion date: August 30, 2026

Study information

• Verified date: January 2024
• Source: Fujian Haixi Pharmaceuticals Co., Ltd.
• Contact: JUNQING LI
• Phone: +86 0591-87519936
• Email: junqing.li[@]hxpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 155
• Est. completion date: August 30, 2026
• Est. primary completion date: August 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• C019199
The C019199 will be taken orally, once a day
• Sintilimab
Sintilimab will be administrated with intravenous infusion, 200mg, every 3 weeks.

Locations

Country	Name	City	State
China	Hunan Cancer Hospital	Changsha	Hunan
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Fujian Haixi Pharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-Limiting Toxicity (DLT)	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.	Cycle 1 (Cycle length=21 days)
Primary	Objective Response Rate (ORR) Based on iRECIST	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.	From date of enrollment until the date of first documented progression or death
Primary	Progression-free Survival (PFS) after administration	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.	From date of enrollment until the date of first documented progression or death
Secondary	Number of Participants With Treatment-emergent Adverse Events( TEAEs )and Serious Adverse Events (SAEs)	A TEAE was defined as an adverse event (AE) that emerged during the time from the first dose of study drug to 28 days following the last dose of study drug,which does not necessarily have a causal relationship with the treatment. A Serious AE is any untoward medical occurrence that at any dose: resulted in death; was life threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria	From the first dose until 28 days after the last dose
Secondary	Cmax	Maximum Plasma Concentration	Cycle 1 Day 1; Cycle 1 Day 21
Secondary	AUC(0-t):	Area under the concentration-time curve (AUC)	Cycle 1 Day 1; Cycle 1 Day 21
Secondary	T1/2	Terminal Half-life	Cycle 1 Day 1; Cycle 1 Day 21
Secondary	Disease Control Rate (DCR) after administration	Disease Control Rate (DCR) is defined as the proportion of patients with complete response, partial response and stable disease.	From date of enrollment until the date of first documented progression or death
Secondary	Duration of Remission (DoR) after administration	Duration of Remission (DoR) is defined as the time from the first documentation of remission (PR or better) to the first documented disease progression evidence (according to iRECIST ) of the responders (who achieve PR or better response).se).	From date of enrollment until the date of first documented progression or death
Secondary	Overall Survival (OS) after administration	OS is defined as the time from the date of study treatment to the date of death due to any cause .	The time from the date of enrollment until death