Clinical trial NCT06166472: A Study to Evaluate the Safety, Tolerance, Pharmacokinetics, and Preliminary Antineoplastic Activity of AK132 in Advanced Malignant Solid Tumor
Official title: A Phase I Study to Evaluate the Safety, Tolerance, Pharmacokinetics, and Preliminary Antineoplastic Activity of The Anti-CLDN18.2 and CD47 Bispecific Antibody AK132 in Advanced Malignant Solid Tumor
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Advanced Malignant Solid Tumor
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2023-12-12
Enrollment: 72
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 A Phase I Study to Evaluate the Safety, Tolerance, Pharmacokinetics, and Preliminary Antineoplastic Activity of The anti-CLDN18.2 and CD47 Bispecific Antibody AK132 in Advanced Malignant Solid Tumor


Eligibility criteria: Inclusion Criteria:

1. The subjects voluntarily participated in the study with full informed consent and signed written informed consent form.
2. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
3. Histologically and/or cytologically confirmed locally advanced unresectable or metastatic malignant solid tumors.
4. The interval between the end of the last systemic anti-tumor treatment and the first dose should be at least 3 weeks.
5. Subjects in the dose expansion phase are required to provide tumor tissue samples.
6. At least one measurable tumor lesion per RECIST v1.1.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Life expectancy ≥ 3 months.
9. Adequate organ function as assessed in the laboratory tests.
10. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose and agree to take effective contraception measures during the study drug administration and within 120 days after the last dose. Male patients with female partners of childbearing potential must agree to take effective contraception measures during the study drug administration and within 120 days after the last dose.

Exclusion Criteria:

1. There is active or untreated brain metastases,Meningeal metastases, spinal cord compression, or leptomeningeal disease.
2. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage (≥ 1/month).
3. Patients who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening.
4. gastrointestinal perforation or gastrointestinal fistula within 6 months before the first dose.
5. clinically significant bleeding symptoms or a clear tendency to bleed within 4 weeks before the first dose.
6. Active malignant tumors within the past 3 years, except for tumors in this study and scured local tumors.
7. History of hemolytic anemia due to any cause within 3 months before the first dose of study drug.
8. Have a history of defects in red blood cell or hemoglobin production or metabolism.
9. Major surgery other than the diagnosis of solid tumors within 28 days prior to the first dose or major surgery is expected during the study.
10. Clinically significant cardiovascular or cerebrovascular disease.
11. Presence of ≥ Grade 2 peripheral neuropathy as defined by NCI CTCAE v5.0.
12. Presence of active diverticulitis.
13. Patients with serious neurological or psychiatric disorders.
14. Pregnant or lactating women.
15. Patients who received palliative local therapy for any tumor lesions within 2 weeks prior to the first dose;and Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor indications within 2 weeks prior to the first dose.
16. Serious adverse reactions in subjects who have previously received anti-PD-1/PD-L1/CTLA-4 or any other immunotherapy or immuno-oncology (IO) drug.
17. Patients who require systemic treatment with glucocorticoids (\> 10 mg/day prednisone or equivalent) or other immunosuppressive drugs within14 days prior to the first dose.
18. Unresolved toxicities during prior anti-tumor therapy with the exception of alopecia/pigmentation.
19. Subjects with a known history of severe hypersensitivity to other monoclonal antibodies. A known history of allergy or hypersensitivity to AK132 or any of its components.
20. Previous use of any antineoplastic drug targeting the CD47-SIRPα pathway or Claudin18.2.
21. Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment, or autoimmune diseases that may relapse or require scheduled treatment as judged by the Investigator.
22. Known active pulmonary tuberculosis.
23. Patients with active hepatitis B or active hepatitis C.
24. Known medical history of immunodeficiency or positive HIV test.
25. Known presence of interstitial lung disease or noninfectious pneumonitis that is currently symptomatic or requires prior systemic glucocorticoid therapy that, in the judgment of the Investigator, may affect the assessment or management of toxicity related to study treatment.
26. Patients with active infection, including those requiring intravenous antibiotics or antifungal therapy for 2 weeks prior to first dose, and unexplained fever during screening (CTCAE≥1, except those determined by the investigator to be neoplasmic).
27. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
28. Live vaccines were administered within 28 days prior to the first dose or were planned to be administered during the study period.
29. Concurrent participation in another clinical study, unless it is an observational, non-interventional clinical study or the follow-up period of an interventional study.
30. Any condition that, in the opinion of the Investigator, may result in a risk when receiving the study drug, or would interfere with the evaluation of the study drug or the safety of patients, or the interpretation of the study results.

Primary outcomes:
measure: dose-limiting toxicity （DLT）、adverse event（AE）、serious adverse event（SAE）
timeFrame: Up to 2 years
measure: Maximum tolerated dose (MTD),RP2D
timeFrame: Up to 2 years
Secondary outcomes:
measure: Pharmacokinetic
timeFrame: Up to 2 years
measure: Immunogenicity assessmen
timeFrame: Up to 2 years
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: Duration of response (DoR)
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Time to response (TTR)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center, Guangzhou, China
state: Guangdong
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Wuhan
country: China
facility: Huazhong University of Science and Technology Tongji Medical College Affiliated Union Hospital
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Provincial Cancer Hospital
state: Hunan
Study officials:
affiliation: Name:Sun Yat-Sen University Cancer Center, Guangzhou, China
name: Ruihua Xu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: