Trial Title:
Study of AK119 and AK 112 With or Without Chemotherapy for Colorectal Cancer Patients
NCT ID:
NCT05846867
Condition:
Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Leucovorin
Oxaliplatin
Fluorouracil
Irinotecan
Calcium
Levoleucovorin
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AK119
Description:
AK119 IV every 2 weeks.intravenous infusion
Arm group label:
AK119 + AK112 20mg/kg +FOLFIRI
Arm group label:
AK119 + AK112 20mg/kg +mFOLFOX6
Arm group label:
AK119 20mg/kg+ AK112 20mg/kg
Arm group label:
AK119 40mg/kg+ AK112 20mg/kg
Intervention type:
Drug
Intervention name:
AK112
Description:
AK112 IV every 2 weeks.intravenous infusion
Arm group label:
AK119 + AK112 20mg/kg +FOLFIRI
Arm group label:
AK119 + AK112 20mg/kg +mFOLFOX6
Arm group label:
AK119 20mg/kg+ AK112 20mg/kg
Arm group label:
AK119 40mg/kg+ AK112 20mg/kg
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
Oxaliplatin: 85mg/m2, intravenous infusion
Arm group label:
AK119 + AK112 20mg/kg +mFOLFOX6
Intervention type:
Drug
Intervention name:
Irinotecan
Description:
Irinotecan 180mg/m2, intravenous infusion
Arm group label:
AK119 + AK112 20mg/kg +FOLFIRI
Intervention type:
Drug
Intervention name:
Calcium folinate
Description:
Calcium folinate: 400mg/m2, intravenous infusion
Arm group label:
AK119 + AK112 20mg/kg +FOLFIRI
Arm group label:
AK119 + AK112 20mg/kg +mFOLFOX6
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
Fluorouracil 400mg/m2, intravenous injection
Arm group label:
AK119 + AK112 20mg/kg +FOLFIRI
Arm group label:
AK119 + AK112 20mg/kg +mFOLFOX6
Summary:
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
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
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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.
2. Age ≥ 18 when signing the informed consent form (ICF), both male and female。
3. 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.
4. 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.
5. 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.
6. 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).
7. 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.
8. The Eastern Cancer Cooperation Organization (ECOG) physical state score is 0 or 1.
9. The expected survival period is ≥ 3 months.
Exclusion Criteria:
1. Pathological examination confirmed other pathological types, such as squamous cell
carcinoma, sarcoma or undifferentiated carcinoma, gastrointestinal stromal tumor,
etc.
2. 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。
3. 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.
4. 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.
5. 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.
6. 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.
7. At the same time, another interventional clinical study was enrolled.
8. 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer Hospital Affiliated to Harbin Medical University
Address:
City:
Harbin
Country:
China
Contact:
Last name:
Yanqiao Zhang, PhD
Start date:
May 10, 2023
Completion date:
July 10, 2025
Lead sponsor:
Agency:
Akeso
Agency class:
Industry
Source:
Akeso
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05846867
