- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05846867
Study of AK119 and AK 112 With or Without Chemotherapy for Colorectal Cancer Patients
May 5, 2023 updated by: Akeso
A Phase Ib/II Study of AK112 and AK119 in Combination With or Without Chemotherapy in the Treatment of Patients With Advanced Microsatellite Stabilized (pMMR/MSS) Colorectal Cancer
This is a phase Ib/II clinical study on AK119 and AK112 combined with or without chemotherapy in advanced microsatellite stabilized (pMMR/MSS) colorectal cancer
Study Overview
Status
Not yet recruiting
Conditions
Intervention / Treatment
Detailed Description
The study included the screening period (no more than 28 days after the subject signed the informed consent form to the first medication), the treatment period (until the investigator assessed that there was no clinical benefit, intolerable toxicity or withdrew the informed consent, whichever occurred first) and the follow-up period (including safety follow-up, disease progress follow-up and survival follow-up).
Subjects will be screened and evaluated within 28 days before the first medication to determine whether they meet the study conditions.
During the screening period, tumor samples of the subjects need to be collected.
Subjects who meet the study conditions will be treated according to the study medication plan until the following conditions occur: the investigator judges that the subject cannot continue to benefit, there is intolerable toxicity, there is a concomitant disease that affects further treatment, the investigator decides, the subject withdraws his informed consent or the treatment needs to be terminated for other reasons specified in the plan (whichever occurs first).
The investigator regularly evaluated the tumor response of all subjects according to RECIST 1.1 standard.
Subjects were evaluated once every 6 weeks (± 7 days) within 54 weeks after enrollment, and then once every 9 weeks (± 7 days).
For subjects undergoing treatment, their clinical decisions are based on the tumor response evaluated by the researchers
Study Type
Interventional
Enrollment (Anticipated)
72
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Zhifang Yao, MD
- Phone Number: 0760-8987 3999
- Email: clinicaltrials@akesobio.com
Study Contact Backup
- Name: Yanqiao Zhang, PhD
- Phone Number: 0451-86298295
- Email: HYDSYLL@163.com
Study Locations
-
-
-
Harbin, China
- Cancer Hospital Affiliated to Harbin Medical University
-
Contact:
- Yanqiao Zhang, phD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Be able to understand and voluntarily sign the written informed consent, which must be signed before the specified research procedure required by the research is implemented.
- Age ≥ 18 when signing the informed consent form (ICF), both male and female。
- Microsatellite stable colorectal cancer confirmed by histopathology; Microsatellite stability was defined as the expression of four common MMR proteins (MLH1, MSH2, MSH6 and PMS2) detected by immunohistochemistry, and all four proteins were positive for pMMR. Or PCR method was used to detect sites (BAT25, BAT26, D5S346, D2S123 and D17S250), and the detection results showed that the stability was microsatellite stability or microsatellite low degree instability.
- The first and second cohorts: recurrent or metastatic colorectal cancer that has failed to undergo at least the second-line standard treatment in the past; The chemotherapy of at least one of the treatment lines is the combination chemotherapy of at least two cytotoxic drugs based on platinum or irinotecan; Definition of treatment failure: disease progression occurs during or after treatment. All patients who change the treatment plan due to drug intolerance are not considered as treatment failure; For subjects who have received induction chemotherapy, concurrent radiotherapy and chemotherapy or adjuvant chemotherapy in the past, if relapse/metastasis occurs within 6 months after the last treatment, the original treatment plan is defined as the first-line treatment plan for the subject.
- The third and fourth cohorts: for patients with advanced colorectal cancer who have not undergone systematic treatment, the recurrence time should be at least 6 months from the end of the last treatment for those who have previously received induction chemotherapy, concurrent radiotherapy and chemotherapy or adjuvant/neoadjuvant chemotherapy.
- Agree to provide archived or freshly obtained tumor tissue samples within 2 years before the first administration (preferably newly obtained tumor tissue samples) About 20 unstained FFPE pathological sections (if the sample size is not enough, only 10 unstained FFPE pathological sections can be provided with the approval of medical inspectors FFPE pathological section).
- According to RECIST v1.1 standard, subjects have at least one measurable target lesion; The focus that has received radiotherapy is not selected as the target lesion, unless the radiotherapy focus is the only measurable focus and the progress is determined according to the imaging, it can be considered as the target lesion.
- The Eastern Cancer Cooperation Organization (ECOG) physical state score is 0 or 1.
- The expected survival period is ≥ 3 months.
Exclusion Criteria:
- Pathological examination confirmed other pathological types, such as squamous cell carcinoma, sarcoma or undifferentiated carcinoma, gastrointestinal stromal tumor, etc.
- Palliative local treatment for non-target lesions within 2 weeks before the first administration; Have received systemic non-specific immunomodulation therapy (such as interleukin, interferon, thymosin, etc.) within 2 weeks before the first administration; Received Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications within 2 weeks before the first administration。
- Had been treated with anti-CD73 inhibitors, immune checkpoint inhibitors (such as anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (such as antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.), immune cell therapy (such as CAR-T) and other therapies aimed at tumor immune mechanism.
- There is a history of gastrointestinal perforation and fistula within 6 months before the first administration. If the perforation or fistula has been removed or repaired, and the researcher judges that the disease has recovered or alleviated, it can be admitted into the group.
- Active or inactive Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis) previously recorded. Inability to swallow, malabsorption syndrome, or uncontrollable nausea, vomiting, diarrhea or other gastrointestinal diseases that seriously affect the use and absorption of drugs.
- Except for the tumor that the subject had at the time of enrollment, there was active malignant tumor in the previous five years. However, the tumors participating in the study and cured local tumors are excluded, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ, localized prostate cancer, etc.
- At the same time, another interventional clinical study was enrolled.
- Receive the last systemic anti-tumor treatment within 3 weeks before the first administration; Received small molecular TKI treatment within 2 weeks before the first administration
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: AK119 20mg/kg+ AK112 20mg/kg
Subjects will receive AK119 plus AK112 via intravenously (IV) Q2W, up to 2 years
|
AK119 IV every 2 weeks.intravenous
infusion
AK112 IV every 2 weeks.intravenous
infusion
|
Experimental: AK119 40mg/kg+ AK112 20mg/kg
Subjects will receive AK119 plus AK112 via intravenously (IV) Q2W, up to 2 years
|
AK119 IV every 2 weeks.intravenous
infusion
AK112 IV every 2 weeks.intravenous
infusion
|
Experimental: AK119 + AK112 20mg/kg +mFOLFOX6
Subjects will receive AK119 and AK112 plus mFOLFOX6 via intravenously (IV)Q2W, up to 12 cycles.
Afterward, AK119 and AK112 will continue to be treated up to 2 years.
|
AK119 IV every 2 weeks.intravenous
infusion
AK112 IV every 2 weeks.intravenous
infusion
Oxaliplatin: 85mg/m2, intravenous infusion
Calcium folinate: 400mg/m2, intravenous infusion
Fluorouracil 400mg/m2, intravenous injection
|
Experimental: AK119 + AK112 20mg/kg +FOLFIRI
Subjects will receive AK119 and AK112 plus FOLFIRI via intravenously (IV)Q2W, up to 12 cycles.
Afterward, AK119 and AK112 will continue to be treated up to 2 years.
|
AK119 IV every 2 weeks.intravenous
infusion
AK112 IV every 2 weeks.intravenous
infusion
Calcium folinate: 400mg/m2, intravenous infusion
Fluorouracil 400mg/m2, intravenous injection
Irinotecan 180mg/m2, intravenous infusion
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of subjects with adverse events (AEs)
Time Frame: From the time of informed consent signed through 90 days after the last dose of study drug
|
AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment.
|
From the time of informed consent signed through 90 days after the last dose of study drug
|
Objective response rate (ORR)
Time Frame: Up to 2 years
|
ORR is defined as the proportion of subjects with confirmed CR or confirmed PR
|
Up to 2 years
|
recommended phaseII dose
Time Frame: 1 year
|
Phase II clinical study recommended dose (RP2D) of AK119 and AK112 combined with or without chemotherapy
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease control rate (DCR)
Time Frame: Up to 2 years
|
DCR is defined as the proportion of subjects with CR, PR, or SD (based on RECIST Version 1.1).
|
Up to 2 years
|
Progression-free survival (PFS)
Time Frame: Up to 2 years
|
PFS is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first (based on RECIST Version 1.1)
|
Up to 2 years
|
Duration of response (DoR)
Time Frame: Up to 2 years
|
DoR is defined as the duration from the first documentation of objective response to the first documented disease progression (based on RECIST Version 1.1) or death due to any cause, whichever occurs first
|
Up to 2 years
|
Time to response (TTR)
Time Frame: Up to 2 years
|
TTR is defined as the time from the start of the treatment to the first objective tumor response observed for patients who achieved CR or PR (based on RECIST Version 1.1)
|
Up to 2 years
|
Total survival time (OS) and 12-month OS rate
Time Frame: Up to 2 years
|
OS defined as the time from the first dose to death from any cause
|
Up to 2 years
|
Maximum observed concentration (Cmax) of AK119 and AK112
Time Frame: From first dose of study drug through last dose up to 100 weeks
|
The PK parameters include serum concentrations of AK119 and AK112 at different timepoints after study drug administration.
|
From first dose of study drug through last dose up to 100 weeks
|
Number of subjects who develop detectable anti-drug antibodies (ADAs)
Time Frame: From first dose of study drug through last dose up to 100 weeks
|
The immunogenicity of AK119 and AK112 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).
|
From first dose of study drug through last dose up to 100 weeks
|
Correlation between biomarkers and efficacy
Time Frame: Up to 2 years
|
Correlation between the expression level of PD-L1 and CD73 biomarkers and efficacy ORR, PFS and OS
|
Up to 2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Yanqiao Zhang, PhD, Cancer Hospital Affiliated to Harbin Medical University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
May 10, 2023
Primary Completion (Anticipated)
May 10, 2024
Study Completion (Anticipated)
July 10, 2025
Study Registration Dates
First Submitted
April 26, 2023
First Submitted That Met QC Criteria
May 5, 2023
First Posted (Estimate)
May 8, 2023
Study Record Updates
Last Update Posted (Estimate)
May 8, 2023
Last Update Submitted That Met QC Criteria
May 5, 2023
Last Verified
May 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Topoisomerase Inhibitors
- Micronutrients
- Vitamins
- Calcium-Regulating Hormones and Agents
- Topoisomerase I Inhibitors
- Antidotes
- Vitamin B Complex
- Fluorouracil
- Oxaliplatin
- Leucovorin
- Irinotecan
- Calcium
- Levoleucovorin
Other Study ID Numbers
- AK119-202
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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