Clinical trial NCT06094556: An Open Phase I Clinical Trial of SHR-1826 for Injection in Patients With Advanced Solid Tumors
Official title: A Multicenter, Open Phase I Clinical Study of Safety, Tolerability, Pharmacokinetics, and Efficacy of SHR-1826 for Injection in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-10-23
Enrollment: 240
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
Primary purpose: TREATMENT

Brief summary: This is an open, multi-center, dose-escalation/dose-expansion/efficacy expansion phase I clinical study to evaluate the tolerability, safety, PK, and immunogenicity of SHR-1826 in patients with advanced malignant solid tumors, and to preliminatively observe its antitumor efficacy. The whole study was divided into three stages: dose increment, dose extension and therapeutic effect extension.


Eligibility criteria: Inclusion Criteria:

1. Able and willing to provide a written informed consent.
2. 18-75 years old ，Male or female.
3. ECOG score is 0 or 1.
4. Subjects with advanced or metastatic solid tumors that have been documented by histopathology and are not responding to or tolerated by standard treatment, or have no effective standard treatment options.
5. Have at least one measurable lesion according to RECIST v1.1 criteria.
6. Expected survival ≥3 months .
7. With good vital organ function.
8. Contraception.

Exclusion Criteria:

1. With untreated or active Central nervous system (CNS) tumor metastasis. Subjects with a history or current history of meningeal metastasis.
2. Previous or co-existing malignant tumors.
3. Spinal cord compression that was not treated radically by surgery and/or radiotherapy was excluded.
4. Patients with uncontrolled tumor-related pain.
5. Received systemic antitumor therapy 4 weeks before starting study treatment; Previously receiving small molecule targeted therapy, the interval of not less than 5 half-lives of the drug can be enrolled.
6. Previously received antibody-coupled drug therapy.
7. Have undergone major surgery other than diagnosis or biopsy within 28 days prior to initial dosing; Minor traumatic surgery within 7 days prior to first dosing.
8. First study subjects receiving \>30Gy non-radical chest radiation within 28 days prior to administration, \>30Gy chest radiation within 24 weeks prior to first administration, and ≤30Gy palliative radiation within 14 days prior to first administration;If previously received radioisotope therapy, the interval of not less than 5 half-lives of the isotope drug can be included.
9. Is participating in another clinical study or the time of first administration is less than 4 weeks from the end of the previous clinical study (last administration), or the 5 half-life of the investigational drug, whichever is the older.
10. The AE caused by previous anti-tumor therapy did not recover to CTCAE v5.0 grade evaluation ≤1.
11. Other severe lung diseases that may interfere with the detection or management of drug-related pulmonary toxicity within the first three months of administration that significantly affect respiratory function; Any autoimmune, connective tissue, or inflammatory disease with lung involvement; Prior left or right total lung resection.
12. Pleural effusion, ascites, or pericardial effusion requiring intervention occurred within 2 weeks prior to the first dose.
13. Have an active autoimmune disease, or other acquired (HIV infection), congenital immunodeficiency disease, or a history of organ transplantation.
14. Have poorly controlled or severe cardiovascular disease.
15. Known hereditary or acquired bleeding and thrombotic tendencies, and clinically significant bleeding symptoms and arterial/venous thrombosis events in the 3 months prior to the first dose.
16. Untreated active hepatitis.
17. Subjects who had a severe infection within 30 days prior to the first dose; Patients with active pulmonary tuberculosis infection within 1 year prior to enrollment were found by medical history or CT examination, or had a history of active pulmonary tuberculosis infection more than 1 year ago but had not received regular treatment.
18. Live attenuated vaccine should be administered within 30 days prior to the first dose.
19. Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study period.
20. Known allergy to any component or excipient of the SHR-1826 product.
21. The presence of other serious physical or mental illnesses or abnormalities in laboratory tests that may increase the risk of participation in the study, or interfere with the study results, as well as conditions that the investigator deems inappropriate to participate in the study.

Primary outcomes:
measure: Dose-limiting toxicity
timeFrame: 21 Days
measure: Maximum tolerated dose or Maximum-administered dose
timeFrame: Approximately 1 year
measure: Recommended Phase 2 dose (RP2D)
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Maximum concentration (Cmax) of SHR-1826
timeFrame: Approximately 2 years
measure: Time to maximum concentration (Tmax) of SHR-1826
timeFrame: Approximately 2 years
measure: Areas under the concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of SHR-1826
timeFrame: Approximately 2 years
measure: Areas under the concentration-time curve from time zero extrapolated to infinity (AUCinf) of SHR-1826
timeFrame: Approximately 2 years
measure: Half-life (t1/2) of SHR-1826
timeFrame: Approximately 2 years
measure: Mean retention times (MRT) of SHR-1826
timeFrame: Approximately 2 years
measure: Clearance rate (CL) of SHR-1826
timeFrame: Approximately 2 years
measure: Volume of distribution at the steady state (Vss) of SHR-1826
timeFrame: Approximately 2 years
measure: Anti-drug antibody of SHR-1826
timeFrame: Approximately 2 years
measure: Objective response rate (ORR)
timeFrame: Approximately 2 years
measure: Duration of response (DoR)
timeFrame: Approximately 2 years
measure: Disease control rate (DCR)
timeFrame: Approximately 2 years
measure: Progression free survival (PFS)
timeFrame: Approximately 2 years
measure: Overall survival (OS)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: