A Phase Ib/II Study of AK104 and AK117 in Combination With or Without Chemotherapy in Advanced Malignant Tumors

Sponsor

Akeso (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05235542

Collaborator

(none)

130

Enrollment

Location

Arms

19.6

Anticipated Duration (Months)

6.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase Ib/II open label, multicenter study to evaluate the efficacy and safety of AK104 (anti-PD-1 and CTLA-4 bispecific antibody) and AK117#AntiCD47 Antibody# combined with or without chemotherapy in advanced malignant tumors

Condition or Disease	Intervention/Treatment	Phase
Advanced Malignant Tumors	Drug: AK104 Drug: AK117 Drug: Capecitabine tablets Drug: Oxaliplatin Drug: Cisplatin Drug: Paclitaxel Drug: Irinotecan Drug: Docetaxel Drug: 5-FU	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

130 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ib/II Study of AK104#PD-1 / CTLA-4 Bispecific Antibody# and AK117#Anti-CD47 Antibody# in Combination With or Without Chemotherapy in Advanced Malignant Tumors

Actual Study Start Date :

Jul 12, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase Ib#Dosage regimen 1# Subjects receive AK104 plus AK117 every 3- week cycle (Q3W) until progression	Drug: AK104 IV infusion,Specified dose on specified days Drug: AK117 IV infusion,Specified dose on specified days
Experimental: Phase Ib#Dosage regimen 2# Subjects receive AK104 plus AK117 every 6- week cycle (Q6W) until progression	Drug: AK104 IV infusion,Specified dose on specified days Drug: AK117 IV infusion,Specified dose on specified days
Experimental: Phase II#Cohort 1# Gastric Cancer or Gastroesophageal Junction Cancer: AK104 + XELOX (Oxaliplatin + Capecitabine)+AK117 every 3- week cycle (Q3W) until progression	Drug: AK104 IV infusion,Specified dose on specified days Drug: AK117 IV infusion,Specified dose on specified days Drug: Capecitabine tablets Oral,Specified dose on specified days Drug: Oxaliplatin IV infusion,Specified dose on specified days
Experimental: Phase II#Cohort 2# Esophageal squamous cell cancer: AK104 + 5-FU/Paclitaxel+Cisplatin± AK117 every 3- week cycle (Q3W) until progression	Drug: AK104 IV infusion,Specified dose on specified days Drug: AK117 IV infusion,Specified dose on specified days Drug: Cisplatin IV infusion,Specified dose on specified days Drug: Paclitaxel IV infusion,Specified dose on specified days Drug: 5-FU IV infusion,Specified dose on specified days
Experimental: Phase II#Cohort 3# Gastric Cancer or Gastroesophageal Junction Cancer or Esophageal squamous cell cancer: AK117 +Paclitaxel/Docetaxel/Irinotecan every 3- or 4- week cycle (Q3W or Q4W) until progression	Drug: AK117 IV infusion,Specified dose on specified days Drug: Paclitaxel IV infusion,Specified dose on specified days Drug: Irinotecan IV infusion,Specified dose on specified days Drug: Docetaxel IV infusion,Specified dose on specified days

Outcome Measures

Primary Outcome Measures

Number of patients with Adverse Events (AEs) [Up to approximately 2 years]
Objective Response Rate (ORR) [Up to approximately 2 years]

Secondary Outcome Measures

Disease control rate (DCR) [Up to approximately 2 years]
Duration of Response (DoR) [Up to approximately 2 years]
Time to response (TTR) [Up to approximately 2 years]
Progression free survival (PFS) [Up to approximately 2 years]
Overall survival (OS) [Up to approximately 2 years]
Maximum observed concentration (Cmax) of AK117 and AK104 [From first dose of study drug to last dose of of study drug]
The endpoints for assessment of PK include serum concentrations of AK117 and AK104 at different timepoints after study drug administration.
Minimum observed concentration (Cmin) of AK117 and AK104 at steady state [From first dose of study drug to last dose of of study drug]
The endpoints for assessment of PK include serum concentrations of AK117 and AK104 at different timepoints after study drug administration.
Number of subjects who develop detectable anti-drug antibodies (ADAs) [From first dose of study drug through 30 days after last dose of study drug]
The immunogenicity of AK117 and AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18 to 75 years old.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Have a life expectancy of at least 3 months.
Phase Ib: Histologically or cytologically confirmed advanced solid tumor.
Phase II: Has histologically confirmed diagnosis of unresectable locally advanced,recurrent or metastatic gastric or GEJ adenocarcinoma or Esophageal squamous cell carcinoma.
Have at least one measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by investigator.
Has adequate organ function.

Exclusion Criteria:

Undergone major surgery within 30 days prior to the first dose of study treatment.
Active central nervous system (CNS) metastases.
History of active autoimmune disease that has required systemic treatment in the past 2 years (i.e.,corticosteroids or immunosuppressive drugs).
Active Hepatitis B or Hepatitis C.
Received previous immunotherapy, including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy and other treatments targeting the mechanism of tumor immunity.
History of severe bleeding tendency or coagulation disorder.