A Phase Ib/II Clinical Study of AK127 in Combination With AK112 in Patients With Advanced Solid Tumors

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

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 Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: AK127 in combination with AK112

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.

• Study Type: Interventional
• Enrollment (Estimated): 216
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: yong b li, PHD; Phone Number: 13023250310; Email: baiyong.li@akesobio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK127 in combination with AK112; Subjects will receive AK127 in combination with AK112 by intravenous administration	Drug: AK127 in combination with AK112; AK127 in combination with AK112 (administered on Day 1 of each cycle, Q3W) up to 2 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment	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
Number of participants with a Dose Limiting Toxicity (DLT)	DLTs will be assessed during the first 3 weeks of treatment for dose-escalation Ib phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle (3 weeks) of treatment	During the first 3 weeks
Number of participants with ORR	Efficacy measures such as overall response rate (ORR), which is the proportion of subjects with CR or PR by investigator based on RECIST v1.1	Up to 2 years
Progression-Free Survival	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first assessed by investigator Per RECIST 1.1.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	DCR, which is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1	Up to 2 years
Duration of response	DoR, which is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.	Up to 2 years
Time to Progress	TTR is defined as the time to response base on RECIST v1.1	Up to 2 years
AUC of AK127 and AK112	Area under the curve (AUC) of AK127 and AK112	Up to 2 years
PK of AK127 and AK112	The endpoints for assessment of PK of AK127 and AK112 include serum concentrations of AK127 and AK112 at different timepoints after AK127 and AK112 administration	Up to 2 years
Cmax of AK127 and AK112	Maximum observed concentration (Cmax) of AK127 and AK112	Up to 2 years
Cmin of AK127 and AK112 at steady state	Minimum observed concentration (Cmin) of AK127 and AK112 at steady state	Up to 2 years
The immunogenicity of AK127 and AK112	The immunogenicity of AK127 and AK112 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs)	Up to 2 years

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Shun Lu, MD, Shanghai Chest Hospital; Principal Investigator: Yun Fan, MD, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: July 11, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 19, 2023

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: AK127-104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No