Clinical trial NCT05393063: A Study to Evaluate the Efficacy and Safety of AK127 in Patients With Advanced Solid Tumors
Official title: A Phase I Open-label Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of AK127 Monotherapy in Patients With Advanced Malignant Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2022-05-26
Enrollment: 36
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 study is to characterize the safety, tolerability and anti-tumor activity of AK127 as a single agent in adult subjects with advanced solid tumor malignancies.

Detailed description: This study is to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK127 as a single agent in adult subjects with advanced solid tumor malignancies. The study, as a dose escalation phase is to determine the maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D) for AK127 as a single agent, and describe Dose Limiting Toxicity (DLT).

Eligibility criteria: Inclusion Criteria:

1. Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed.
2. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
4. Life expectancy ≥3 months.
5. Histologically or cytologically documented advanced or metastatic solid tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject is not suitable for standard therapy.
6. Adequate organ function.
7. Patients of childbearing potential must agree to use effective contraceptive measures.

Exclusion Criteria:

1. The patient has received prior immunotherapy against TIGIT target.
2. Not currently enrolled in any other clinical study.
3. Receipt of any anticancer therapy within 4 weeks or within 5 half-lives of the drug prior to the first dose of AK127.
4. Symptomatic central nervous system metastases.
5. Active malignancies within the past 1 years, with the exception of tumors in this study and cured local tumors.
6. Active autoimmune disease requiring systemic treatment prior to the start of study treatment.
7. There is a history of major diseases 1 year prior to the first dose.
8. Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose.
9. Received chest radiation therapy prior to the first dose.
10. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
11. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
12. Receipt of live or attenuated vaccination within 4 weeks prior to the first dose of AK127.
13. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
14. Known history of active tuberculosis.
15. History of organ transplant or hematopoietic stem cell.
16. History of primary immunodeficiency.
17. Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
18. Other cases deemed inappropriate by the investigator.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first
measure: Number of participants with a Dose Limiting Toxicity (DLT)
timeFrame: During the first 21 days
Secondary outcomes:
measure: PFS
timeFrame: Up to 2 years
measure: ORR
timeFrame: Up to 2 years
measure: DCR
timeFrame: Up to 2 years
measure: DOR
timeFrame: Up to 2 years
measure: TTR
timeFrame: Up to 2 years
measure: Area under the Concentration-Time Curve (AUC) of AK127
timeFrame: Cycle 1 and 4: Predose, Post-dose-5min,2 hours, 24 hours, Day 4,8 and 15; Cycle 2,3,5,6: Predose and Post-dose-5min; then Predose at Day 1, every 2 cycles (cycle length 21 days),Day30 after last dose; Up to 2 years and 1 months
measure: Maximum observed concentration (Cmax) of AK127
timeFrame: Cycle 1 and 4: Predose, Post-dose-5min,2 hours, 24 hours, Day 4,8 and 15; Cycle 2,3,5,6: Predose and Post-dose-5min; then Predose at Day 1, every 2 cycles (cycle length 21 days),Day30 after last dose; Up to 2 years and 1 months
measure: Minimum observed concentration (Cmin) of AK127 at steady state
timeFrame: Cycle 1 and 4: Predose, Post-dose-5min,2 hours, 24 hours, Day 4,8 and 15; Cycle 2,3,5,6: Predose and Post-dose-5min; then Predose at Day 1, every 2 cycles (cycle length 21 days),Day30 after last dose; Up to 2 years and 1 months
measure: Number and Percentage of Subjects with Anti-Drug Antibodies(ADAs) to AK127
timeFrame: Predose on Day 1 at Cycle 1-6, then Predose at Day 1, every 2 cycles,Day30 after last dose; Up to 2 years and 1 months
Other outcomes:
Locations:
Study officials:
affiliation: Shanghai Chest Hospital
name: Shun Lu, Chief doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhejiang Cancer Hospital
name: Yun Fan, Chief doctor
role: PRINCIPAL_INVESTIGATOR
References: