Phase I Clinical Study of SHR-5495 in the Treatment of Patients With Advanced Malignant Tumors

Advanced Malignant Tumor Clinical Trial

Official title:

A Multicenter, Open-label Phase I Clinical Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SHR-5495 for Injection in Patients With Advanced Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06059508
• Other study ID #: SHR-5495-I-101
• Status: Recruiting
• Phase: Phase 1
• Start date: October 25, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2023
• Source: Suzhou Suncadia Biopharmaceuticals Co., Ltd.
• Contact: Li Song
• Phone: +86-0518-81220121
• Email: li.song[@]hengrui.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is an open, multicenter, dose-increasing/dose-expanding/efficacy expanding Phase I clinical study aimed at evaluating the tolerance, safety, PK, PD, and immunogenicity of SHR-5495 in the treatment of advanced malignant tumor patients, and preliminarily observing its anti-tumor efficacy. The entire study was divided into three stages: dose escalation, dose extension, and efficacy extension.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age range from 18 to 70 years old (including 18 and 70 years old), both male and female

2. Pathologically confirmed advanced malignant tumors that have failed sufficient standard treatment or have no effective standard treatment plan

3. ECOG score: 0-1

4. Expected survival time = 12 weeks

5. Existence of measurable lesions that meet RECIST 1.1 standards

6. Sufficient Hematology and end organ function shall be completed within 7 days before the first study treatment

7. Left ventricular Ejection fraction (LVEF) = 50% within 28 days before the first administration

8. Women of childbearing age must carry out serum Pregnancy test within 7 days before the first administration, and the result is negative. Female subjects of childbearing age and male subjects with partners of childbearing age must agree to use efficient methods of contraception or abstinence within at least 26 weeks (female subjects) or 14 weeks (male subjects) from the date of signing the informed consent form until the last administration

9. The patient voluntarily joined this study, signed an informed consent form, had good understand the research procedures, and have signed informed consent

Exclusion Criteria:

1. Has received treatment with interleukin

2. Previously received immune checkpoint inhibitors

3. Central nervous system metastasis with clinical symptoms in patients

4. The third space effusion with clinical symptoms needs repeated drainage, such as pericardial effusion, Pleural effusion and peritoneal effusion that cannot be controlled after pumping or other treatment

5. Subjects who received anti-tumor therapy and systemic immune stimulation therapy within 4 weeks prior to the first dose of the study drug; Received traditional Chinese patent medicines and simple preparations anti-tumor treatment within 2 weeks before the first dose of study drug

6. Subjects who received>30Gy of non thoracic radical radiation therapy within 28 days before the first medication, those who received>30Gy of chest radiation therapy within 24 weeks before the first medication, and those who received = 30Gy of palliative radiation therapy within 14 days before the first medication

7. Subjects who have received systemic Immunosuppressive drug treatment within 2 weeks before the first administration, or who are expected to require systemic immunosuppressive drug treatment during the study treatment.

8. Patients who have not recovered to = CTCAE level 1 (CTCAE v5.0) due to adverse events caused by previous treatment

9. Having autoimmune diseases

10. Other malignant tumors within 2 years before screening, excluding fully treated cervical Carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and ductal Carcinoma in situ after radical surgery

11. Subjects with known or suspected interstitial pneumonia; Other moderate to severe lung diseases that may interfere with the detection or treatment of drug-related pulmonary toxicity and seriously affect respiratory function

12. Subjects with severe cardio cerebral Vascular disease

13. Clinically significant bleeding symptoms or tendency to bleed within one month before the first administration

14. Arteriovenous thrombotic events that occurred within 3 months before the first administration

15. Uncontrolled tumor related pain or symptomatic hypercalcemia. Subjects who require painkillers must already have a stable painkillers treatment plan at the time of entry into the study; Symptomatic lesions suitable for palliative radiotherapy should be treated before entering the study

16. Active hepatitis B or active hepatitis C

17. Abnormal electrocardiogram (ECG) examination, judged by the researcher to have clinical significance

18. Have a history of immune deficiency

19. Evidence of active tuberculosis infection within 1 year prior to the first administration, or a history of active tuberculosis infection more than 1 year ago without formal treatment

20. Serious infection occurred within 4 weeks before the first administration; Active infections that have received therapeutic intravenous or oral antibiotics within 2 weeks prior to starting the study.

21. History of live attenuated vaccine administration within 28 days prior to initial administration or expected study period

22. Within 28 days prior to the first administration, major surgeries other than diagnosis or biopsy have been performed; Traumatic minor surgery experienced within 7 days prior to first administration

23. Subjects who have previously received or are preparing to receive allogeneic bone marrow transplantation or solid organ transplantation

24. Has a history of severe allergic reactions to other monoclonal antibodies/fusion protein drugs, and is allergic to any component of the research treatment plan

25. Female subjects during pregnancy, lactation, or planning to conceive during the study period

26. The subject has a known history of psychotropic substance abuse, alcoholism, or drug abuse

27. Researchers believe that any other medical, psychiatric, or social condition may interfere with the subjects' rights, safety, health, or ability to sign informed consent, cooperate and participate in the study, or interfere with the evaluation of the study medication

Related Conditions & MeSH terms

• Advanced Malignant Tumor
• Neoplasms

Intervention

Drug:
• SHR-5495 for injection
SHR-5495 for injection

Locations

Country	Name	City	State
China	Shandong First Medical University Affiliated Cancer Hospital	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Suzhou Suncadia Biopharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limited toxicity (DLT) of SHR-5495		up to 21 days
Primary	AEs+SAEs		from the first drug administration to within 90 days for the last treatment dose
Primary	Maximum tolerated dose(MTD)of SHR-5495		up to 21 days
Primary	Maximum administrated dose(MAD)of SHR-5495		up to 21 days
Primary	Recommended Phase II Dose (RP2D) of SHR-5495		up to 21 days
Secondary	Evaluation of pharmacokinetic parameter of SHR-5495: Cmax		12 months
Secondary	Evaluation of pharmacokinetic parameter of SHR-5495: Tmax		12 months
Secondary	Evaluation of pharmacokinetic parameter of SHR-5495: AUClast		12 months
Secondary	Evaluation of pharmacokinetic parameter of SHR-5495: AUCinf		12 months
Secondary	Evaluation of pharmacokinetic parameter of SHR-5495: t1/2		12 months
Secondary	Evaluation of pharmacokinetic parameter of SHR-5495: CL		12 months
Secondary	Evaluation of pharmacokinetic parameter of SHR-5495: Vss		12 months
Secondary	Receptor occupancy rate		12 months
Secondary	Objective Response Rate (ORR)		From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Secondary	Duration of response (DoR)		From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Secondary	Disease control rate (DCR)		From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Secondary	Progression free survival(PFS)		From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Secondary	Overall survival (OS)		From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Secondary	Target cell count		12 months