Clinical trial NCT05951608: A Phase Ib/II Clinical Study of AK127 in Combination With AK112 in Patients With Advanced Solid Tumors
Official title: A Phase Ib/II Open-label Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of AK127 in Combination With AK112 in Patients With Advanced Malignant Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2023-07-19
Enrollment: 216
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 Ib/II Open-label Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of AK127 in combination with AK112 in Patients with Advanced Malignant Tumors

Detailed description: The study consisted of two parts. The first part, Phase Ib is to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity of AK127 in combination with AK112 in adult subjects with advanced solid tumor malignancies. The part, as a dose escalation phase is to determine the maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D) for AK127 in combination with AK112, and describe Dose Limiting Toxicity (DLT).The second part, Phase II is to Evaluate the anti-tumor activity of AK127 in combination with AK112 in different tumor species cohorts.

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. The patient had previously been treated with anti-PD -(L)1 and anti-VEGF targets.
3. Currently enrolled in any other clinical study.
4. Receipt of any anticancer therapy within 4 weeks prior to the first dose of Investigational drug;
5. Symptomatic central nervous system metastases.
6. Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors
7. Active autoimmune disease requiring systemic treatment prior to the start of study treatment.
8. There is a history of major diseases 1 year prior to the first dose.
9. Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose
10. Received chest radiation therapy prior to the first dose
11. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
12. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
13. Receipt of live or attenuated vaccination within 4 weeks prior to the first dose of Investigational drug.
14. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
15. Known history of active tuberculosis.
16. History of organ transplant or hematopoietic stem cell.
17. History of primary immunodeficiency.
18. 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.
19. 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 3 weeks
measure: Number of participants with ORR
timeFrame: Up to 2 years
measure: Progression-Free Survival
timeFrame: Up to 2 years
Secondary outcomes:
measure: Disease control rate
timeFrame: Up to 2 years
measure: Duration of response
timeFrame: Up to 2 years
measure: Time to Progress
timeFrame: Up to 2 years
measure: AUC of AK127 and AK112
timeFrame: Up to 2 years
measure: PK of AK127 and AK112
timeFrame: Up to 2 years
measure: Cmax of AK127 and AK112
timeFrame: Up to 2 years
measure: Cmin of AK127 and AK112 at steady state
timeFrame: Up to 2 years
measure: The immunogenicity of AK127 and AK112
timeFrame: Up to 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Shanghai Chest Hospital
name: shun lu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhejiang Cancer Hospital
name: yun fan, MD
role: PRINCIPAL_INVESTIGATOR
References: