Clinical trial NCT05653284: A Study of AK130 in Patients With Advanced Malignant Tumors
Official title: A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AK130 (TIGIT/TGF-β Bifunctional Fusion Protein) in Patients With Advanced Malignant Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Malignant Tumors
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2022-12-16
Enrollment: 19
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: A Phase I open label, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of AK130 (TIGIT/TGF-β bifunctional fusion protein) in patients with advanced malignant tumors.


Eligibility criteria: Inclusion Criteria:

1. Written and signed informed consent and any locally required authorization obtained from the subject/legal representative.
2. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
3. Life expectancy ≥3 months.
4. Histologically or cytologically documented unresectable advanced or metastatic malignant tumor that has failed or intolerant of standard therapy, or for which no effective standard therapy is available.
5. Subject must have at least one measurable lesion according to RECIST Version1.1.
6. Adequate organ function.

Exclusion Criteria:

1. Any malignancy other than the disease under study within the past 3 years except for radically cured local cancers, such as basal cell skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of breast.
2. Receipt of any anti-TIGIT, anti-TGF-β treatment.
3. Experienced a toxicity that led to permanent discontinuation of prior immunotherapy. All AEs while receiving prior immunotherapy have not completely resolved or resolved to Grade 1 prior to screening, required the use of additional immunosuppression other than corticosteroids.
4. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5.0 Grade 0 or 1，or to levels dictated in the inclusion/exclusion criteria, except toxicities not considered a safety risk (e.g., alopecia, neuropathy, or asymptomatic laboratory abnormalities).
5. Major surgical procedure within 4 weeks prior to the first dose of AK130 or still recovering from prior surgery.
6. History of organ transplant.
7. Known allergy or reaction to any component of the AK130 formulation. History of severe hypersensitivity reactions to other mAbs.

Primary outcomes:
measure: Incidence and severity of participants with adverse events (AEs)
timeFrame: From time ICF is signed until 90 days after last dose of AK130
measure: Number of participants with DLTs
timeFrame: During the first four weeks of treatment with AK130
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to approximately 2 years
measure: Disease control rate (DCR)
timeFrame: Up to approximately 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 2 years
measure: Overall survival (OS)
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
measure: Time to response (TTR)
timeFrame: Up to approximately 2 years
measure: Maximum observed concentration (Cmax) of AK130
timeFrame: From first dose of study drug through end of treatment (up to approximately 2 years)
measure: Minimum observed concentration(Cmin) of AK130
timeFrame: From first dose of study drug through end of treatment (up to approximately 2 years)
measure: Area under the curve (AUC) of AK130 for assessment of pharmacokinetics
timeFrame: From first dose of study drug through end of treatment (up to approximately 2 years)
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From first dose of study drug through 30 days after last dose of study drug
Other outcomes:
Locations:
city: Jinan
country: China
facility: The Cancer Hospital Affiliated to Shandong First Medical University
state: Shandong
Study officials:
affiliation: The Cancer Hospital Affiliated to Shandong First Medical University
name: Jinming Yu
role: PRINCIPAL_INVESTIGATOR
References: