Clinical trial NCT05142423: A Study of AK109 Combined With AK104 in Patients With Advanced Solid Tumors
Official title: An Open Label, Multi-center, Phase Ib/II Clinical Study of AK109 Combined With AK104 to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2021-12-02
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, open label, phase Ib/II clinical study of AK109 and AK104 to evaluate the safety, tolerability, effectiveness, pharmacokinetic characteristics in advanced solid tumors .


Eligibility criteria: Inclusion Criteria:

1. Written and signed informed consent.
2. Age ≥ 18 years and ≤ 75 years.
3. ECOG Performance Status of 0 or 1.
4. Estimated life expectancy of ≥3 months.
5. Histologically or cytologically documented, locally advanced or metastatic solid tumours (NSCLC, mCRC, HCC, GEJ, etc. ), for which standard therapy does not exist or has proven ineffective or intolerable.
6. At least one radiographically measurable lesion per RECIST 1.1.
7. Tumor biopsy (during advanced stage) available.
8. Adequate organ function.
9. Female participants of childbearing potential and male partners with female partners of childbearing potential must agree to use effective barrier methods of contraception during the study and for 120 days after last dose of study drug.

Exclusion Criteria:

1. Other documented active malignancies other than for this trial within 3 years.
2. Participation in other clincial trials simultaneously.
3. Use of systemic anti-tumor treatments with 4 weeks, non-specific immunomodulating agents within 2 weeks.
4. Prior exposure to other T cell coregulatory proteins except for PD-1/PD-L1 inhibitors (apart from cohort B, i.e. treatment naive HCC patients).
5. Current use corticosteroids/immunosuppressive agents, permanently discontinuation of study drug, or having any unresolved irAEs (≥grade 2) from prior PD-1/PD-L1 inhibitors treatment.
6. Central nervous system (CNS) metastasis, meningeal metastasis, spinal cord compression, or leptomeningeal disease.
7. Uncontrolled pleural/pericardial or peritoneal effusion.
8. History of hemorrhagic event need blood transfusion, invasive approaches to intervene, or hospitalization within 3 months, or having high risks of bleeding.
9. Any thromboembolic event, non-gastrointestinal fistula or female genital tract fistula within 6 months.
10. Uncontrolled gastrointestinal diseases.
11. Use of NSAIDs and anticoagulant agents within 7 days.
12. Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks.
13. Severe or uncontrolled hypertension and cardiovascular/cerebrovascular diseases.
14. Uncontrolled comorbidities need corticosteroids using.
15. Active or prior autoimmune disease or history of immunodeficiency.
16. History of interstitial lung disease.
17. Known history of active tuberculosis (TB).
18. Evidence of active infections including hepatitis B and C.
19. Use of anti-infectious agents within 2 weeks.
20. History of human immunodeficiency virus (HIV) infections.
21. Active syphilis infections.
22. Any unresolved toxicities (≥grade 2) from previous anti-cancer therapies.
23. Mental illness, drug abuse, or alcohol dependence that may affect compliance with the test requirements.

Primary outcomes:
measure: Number of subjects experiencing dose-limiting toxicities(DLTs)
timeFrame: Up to 21 days
measure: Incidences and severity of AE
timeFrame: Up to 2 years
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
measure: Duration of response (DoR)
timeFrame: Up to 2 years
measure: Time to response (TTR)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
measure: Correlation analysis of PD-L1 expression with efficacy
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: First affliated hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: The First Affiliated Hospital of Medicine College, Zhejiang University
name: Nong Xu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Chinese PLA General Hospital
name: Jianming Xu, MD
role: PRINCIPAL_INVESTIGATOR
References: