Back to resultsA Study of AK112 With or Without AK117 in Metastatic Colorectal Cancer
Primary Purpose
Metastatic Colorectal Cancer
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
AK112
AK117
Oxaliplatin
Capecitabine
Irinotecan
Leucovorin
5-fluorouracil
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically proven diagnosis of colorectal adenocarcinoma
- Part1: Initially unresectable metastatic colorectal cancer(metastasis detected at diagnosis) not previously systemic antitumor therapy for metastatic disease.
- Part2: Prior radiation therapy for lesions which were primary or metastatic from colorectal cancer.Patient must have received at least 2 prior line and no more than 4 prior lines of systemic anticancer therapy.
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Measurable disease as defined by RECIST v1.1
- Adequate hematologic and end-organ function
Exclusion Criteria:
- Known MSI-H(Microsatellite-Instability-High) or dMMR(Mismatch Repair-Deficient)
- Prior treatment with immunotherapy, including immune checkpoint inhibitors , immune checkpoint agonists, immune cell therapy and any treatment targeting tumor immune pathway
- History of autoimmune disease
- Prior allogeneic stem cell or solid organ transplantation
- Positive test for human immunodeficiency virus,Active hepatitis B or hepatitis C
- Receipt of a live, attenuated vaccine within 30 days prior to randomization, during treatment
- Pregnancy or lactation
- Dysphagia
Sites / Locations
- The Sixth Hospital,Sun Yat-sen UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Active Comparator
Experimental
Experimental
Arm Label
Part 1_Chemotherapy Regimen Selection Stage Group A(AK112+AK117+XELOX)
Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI)
Part 1_Expansion Stage Group A(AK112+Chemotherapy)
Part 1_Expansion Stage Group B(AK112+AK117+Chemotherapy)
Part 1_Expansion Stage Group C(Bevacizumab+Chemotherapy)
Part 2 cohort 1(AK112)
Part 2 cohort 2(AK112+AK117)
Arm Description
AK112+AK117+XELOX AK112 20 mg/kg iv day 1, AK117 20 mg/kg iv day 1 and day 8 and day15, XELOX(Oxaliplatin 130 mg/sqm iv day 1, Capecitabine via oral, the total daily dose was 2000mg/sqm, day1-14)(to be repeated every 3 weeks for a maximum of 6 cycles) If no progression occurs during AK112 plus AK117 plus XELOX, patients will receive maintenance capecitabine plus AK112 plus AK117(day 1and day 8 and day15) at the same dose used at the last cycle of the induction treatment. Capecitabine plus AK112 plus AK117 will be repeated every 3 weeks until disease progression, unacceptable toxicity or patient's refusal.
AK112+AK117+FOLFOXIRI AK112 20 mg/kg iv day 1, AK117 20 mg/kg iv day 1and day 8, FOLFOXIRI(Irinotecan 150-165 mg/sqm iv day 1, Oxaliplatin 85 mg/sqm iv day 1, Leucovorin(LV) 400 mg/sqm iv day 1, 5-fluorouracil(5-FU) 2400-2800 mg/sqm 48 h-continuous infusion, starting on day 1) (to be repeated every 2 weeks for a maximum of 8 cycles) If no progression occurs during AK112 plus AK117 plus FOLFOXIRI, patients will receive maintenance 5-FU/LV plus AK112 plus AK117(day 1and day 8) at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 plus AK117 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.
AK112+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 20 mg/kg iv day 1, XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)
AK112+AK117+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) AK112 20 mg/kg iv day 1, AK117 20 mg/kg iv day 1(qw), XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)
Bevacizumab+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage) Bevacizumab 5 mg/kg iv day 1(q2w) or 7.5 mg/kg iv day 1(q3w), XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)
Subjects receive AK112 until disease progression or unacceptable toxicity AK112 20 mg/kg iv day 1(to be repeated every 3 weeks until disease progression, unacceptable toxicity or patient's refusal)
Subjects receive AK117 and AK112 until disease progression or unacceptable toxicity AK112 20 mg/kg iv day 1, AK117 20 mg/kg iv day 1(qw)(to be repeated every 3 weeks until disease progression, unacceptable toxicity or patient's refusal)
Outcomes
Primary Outcome Measures
Objective response rates (ORR)
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1
Number of participants with adverse events (AEs)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Secondary Outcome Measures
Disease control rate (DCR)
Disease control rate (DCR) is defined as the proportion of subjects with CR, PR, or stable disease(SD) based on RECIST V1.1
Duration of response (DOR)
DOR is defined for participants who had an objective response as the time from the first occurrence of a documented confirmed response (CR or PR) to the date of disease progression per RECIST v1.1 or death from any cause,whichever occurred first
Time to response (TTR)
TTR is defined for participants who had an objective response as the time from the start of treatment to the first occurrence of a documented unconfirmed response (CR or PR) .
Progression-free survival (PFS)
PFS is defined as the time from the start of treatment till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).
Progression-free survival 2 (PFS2)
PFS 2 is defined as the time from the start of treatment till the second documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).
Overall survival (OS)
Overall survival is defined as the time from the start of treatment until death due to any cause.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05382442
Brief Title
A Study of AK112 With or Without AK117 in Metastatic Colorectal Cancer
Official Title
A Phase II Study of AK112 With or Without AK117 for Patients With Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 27, 2022 (Actual)
Primary Completion Date
October 17, 2022 (Anticipated)
Study Completion Date
January 7, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akeso
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This trial is a Phase II study. The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of AK112 with or without AK117 in participants with metastatic colorectal cancer who are not suitable for surgery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
114 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part 1_Chemotherapy Regimen Selection Stage Group A(AK112+AK117+XELOX)
Arm Type
Experimental
Arm Description
AK112+AK117+XELOX
AK112 20 mg/kg iv day 1, AK117 20 mg/kg iv day 1 and day 8 and day15, XELOX(Oxaliplatin 130 mg/sqm iv day 1, Capecitabine via oral, the total daily dose was 2000mg/sqm, day1-14)(to be repeated every 3 weeks for a maximum of 6 cycles)
If no progression occurs during AK112 plus AK117 plus XELOX, patients will receive maintenance capecitabine plus AK112 plus AK117(day 1and day 8 and day15) at the same dose used at the last cycle of the induction treatment. Capecitabine plus AK112 plus AK117 will be repeated every 3 weeks until disease progression, unacceptable toxicity or patient's refusal.
Arm Title
Part 1_Chemotherapy Regimen Selection Stage Group B(AK112+AK117+FOLFOXIRI)
Arm Type
Experimental
Arm Description
AK112+AK117+FOLFOXIRI
AK112 20 mg/kg iv day 1, AK117 20 mg/kg iv day 1and day 8, FOLFOXIRI(Irinotecan 150-165 mg/sqm iv day 1, Oxaliplatin 85 mg/sqm iv day 1, Leucovorin(LV) 400 mg/sqm iv day 1, 5-fluorouracil(5-FU) 2400-2800 mg/sqm 48 h-continuous infusion, starting on day 1) (to be repeated every 2 weeks for a maximum of 8 cycles)
If no progression occurs during AK112 plus AK117 plus FOLFOXIRI, patients will receive maintenance 5-FU/LV plus AK112 plus AK117(day 1and day 8) at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus AK112 plus AK117 will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.
Arm Title
Part 1_Expansion Stage Group A(AK112+Chemotherapy)
Arm Type
Experimental
Arm Description
AK112+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage)
AK112 20 mg/kg iv day 1, XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)
Arm Title
Part 1_Expansion Stage Group B(AK112+AK117+Chemotherapy)
Arm Type
Experimental
Arm Description
AK112+AK117+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage)
AK112 20 mg/kg iv day 1, AK117 20 mg/kg iv day 1(qw), XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)
Arm Title
Part 1_Expansion Stage Group C(Bevacizumab+Chemotherapy)
Arm Type
Active Comparator
Arm Description
Bevacizumab+Chemotherapy(Decided by Chemotherapy Regimen Selection Stage)
Bevacizumab 5 mg/kg iv day 1(q2w) or 7.5 mg/kg iv day 1(q3w), XELOX or FOLFOXIRI(the same dosage, frequency and duration with Chemotherapy Regimen Selection Stage)
Arm Title
Part 2 cohort 1(AK112)
Arm Type
Experimental
Arm Description
Subjects receive AK112 until disease progression or unacceptable toxicity
AK112 20 mg/kg iv day 1(to be repeated every 3 weeks until disease progression, unacceptable toxicity or patient's refusal)
Arm Title
Part 2 cohort 2(AK112+AK117)
Arm Type
Experimental
Arm Description
Subjects receive AK117 and AK112 until disease progression or unacceptable toxicity
AK112 20 mg/kg iv day 1, AK117 20 mg/kg iv day 1(qw)(to be repeated every 3 weeks until disease progression, unacceptable toxicity or patient's refusal)
Intervention Type
Drug
Intervention Name(s)
AK112
Intervention Description
AK112 via intravenous (IV) infusion until disease progression or unacceptable toxicity
Intervention Type
Drug
Intervention Name(s)
AK117
Intervention Description
AK117 via intravenous (IV) infusion until disease progression or unacceptable toxicity
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Oxaliplatin via IV infusion
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine via oral,The total daily dose was 2000mg/sqm, Each cycle was administered for 2 consecutive weeks, followed by a week of rest, with a treatment cycle every 21 days
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Irinotecan via IV infusion
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Intervention Description
Leucovorin via IV infusion
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Intervention Description
5-fluorouracil via IV infusion
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Bevacizumab via IV infusion
Primary Outcome Measure Information:
Title
Objective response rates (ORR)
Description
ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1
Time Frame
Up to approximately 2 years
Title
Number of participants with adverse events (AEs)
Description
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
Disease control rate (DCR)
Description
Disease control rate (DCR) is defined as the proportion of subjects with CR, PR, or stable disease(SD) based on RECIST V1.1
Time Frame
Up to approximately 2 years
Title
Duration of response (DOR)
Description
DOR is defined for participants who had an objective response as the time from the first occurrence of a documented confirmed response (CR or PR) to the date of disease progression per RECIST v1.1 or death from any cause,whichever occurred first
Time Frame
Up to approximately 2 years
Title
Time to response (TTR)
Description
TTR is defined for participants who had an objective response as the time from the start of treatment to the first occurrence of a documented unconfirmed response (CR or PR) .
Time Frame
Up to approximately 2 years
Title
Progression-free survival (PFS)
Description
PFS is defined as the time from the start of treatment till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).
Time Frame
Up to approximately 2 years
Title
Progression-free survival 2 (PFS2)
Description
PFS 2 is defined as the time from the start of treatment till the second documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).
Time Frame
Up to approximately 2 years
Title
Overall survival (OS)
Description
Overall survival is defined as the time from the start of treatment until death due to any cause.
Time Frame
Up to approximately 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven diagnosis of colorectal adenocarcinoma
Part1: Initially unresectable metastatic colorectal cancer(metastasis detected at diagnosis) not previously systemic antitumor therapy for metastatic disease.
Part2: Prior radiation therapy for lesions which were primary or metastatic from colorectal cancer.Patient must have received at least 2 prior line and no more than 4 prior lines of systemic anticancer therapy.
Eastern Cooperative Oncology Group performance status of 0 or 1
Measurable disease as defined by RECIST v1.1
Adequate hematologic and end-organ function
Exclusion Criteria:
Known MSI-H(Microsatellite-Instability-High) or dMMR(Mismatch Repair-Deficient)
Prior treatment with immunotherapy, including immune checkpoint inhibitors , immune checkpoint agonists, immune cell therapy and any treatment targeting tumor immune pathway
History of autoimmune disease
Prior allogeneic stem cell or solid organ transplantation
Positive test for human immunodeficiency virus,Active hepatitis B or hepatitis C
Receipt of a live, attenuated vaccine within 30 days prior to randomization, during treatment
Pregnancy or lactation
Dysphagia
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Weifeng Song, MD
Phone
+86(0760)89873999
Email
clincialtrails@akesobio.com
Facility Information:
Facility Name
The Sixth Hospital,Sun Yat-sen University
City
Guanzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
A Study of AK112 With or Without AK117 in Metastatic Colorectal Cancer
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