Trial Title:
AK112 Combined With Chemotherapy as the First-line Treatment in Advanced Esophageal Squamous Cell Carcinoma Patients
NCT ID:
NCT06489197
Condition:
ESCC
Advanced Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Paclitaxel
Cisplatin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ivonescimab combined with albumin paclitaxel and cisplatin
Description:
Ivonescimab (20mg/kg, intravenous infusion, d1, Q3W) combined with albumin paclitaxel
(220mg/m2, intravenous infusion, d1, Q3W) and cisplatin (75mg/m2, intravenous infusion,
d1, Q3W), of which the maximum treatment time of chemotherapy was up to six cycles, and
the maximum treatment time of AK112 was 24 months.
Arm group label:
Experimental arm
Summary:
This is a single arm，phase 2 study evaluating the safety and efficacy of
Ivonescimab(AK112) combined with chemotherapy in the treatment of advanced esophageal
squamous cell carcinoma (ESCC). In this study, patients with advanced esophageal squamous
cell carcinoma who had not received any systematic treatment in the past will be
enrolled.
The research will be conducted in two stages. In the first part, 6 patients were enrolled
in the group. After the last subject in the group completed at least 21 days of
observation after the first medication, the researchers will conduct a preliminary safety
and effectiveness assessment. If the safety and tolerability are good, it will enter the
second expansion part till the study enrolled 30 patients. Patients who met the inclusion
criteria were treated with AK112 (20mg/kg, intravenous infusion, d1, Q3W) in combination
with albumin paclitaxel (220mg/m2, intravenous infusion, d1, Q3W) and cisplatin (75mg/m2,
intravenous infusion, d1, Q3W), of which the maximum treatment time of chemotherapy was
up to six cycles, and the maximum treatment time of AK112 was 24 months. Patients
received regular and periodic reviews, with imaging evaluations every 6 weeks.
Detailed description:
Part 1: Safety introduction phase, evaluate the safety and tolerability of AK112 combined
with chemotherapy (albumin paclitaxel and cisplatin). Plan to enroll 6 advanced ESCC
subjects who have not undergone any systematic anti-tumor treatment in the past. After
completing at least 21 days of observation after the first medication of the last
enrolled subject, the researchers will conduct preliminary safety and efficacy
evaluations. If the safety and tolerability are good, and preliminary therapeutic signals
are observed, it will enter the stage of expansion into the group. Researchers may also
discuss adjusting the AK112 dose, albumin paclitaxel dose, or cisplatin dose based on the
specific situation during the DLT observation period, and then enroll new subjects for
the safety introduction phase evaluation of the treatment plan in the study group.
DLT definition: Within 21 days after the first administration, the subject experiences
the following drug-related toxic reactions (according to NCI CTC AE 5.0 toxicity
evaluation criteria): hematological toxicity level 4 or above or non hematological
toxicity level 3 or above (excluding hair loss).
Part 2: Expand the enrollment stage, to further evaluate the efficacy and safety of AK112
combined with albumin paclitaxel and cisplatin in first-line treatment of advanced ESCC.
During the expansion phase, 30 subjects will be enrolled, and a comprehensive discussion
will be conducted based on the safety and efficacy data from the safety introduction
phase to determine the dosage.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed the informed consent；
2. Male or female patients ≥18 and ≤ 75 years old;
3. ECOG physical status score is 0 or 1;
4. Patients with non resectable or metastatic advanced ESCC confirmed by pathological
ocytological examination;
5. No previous systemic treatment;
6. Expected survival time ≥ 3 months;
7. Patients must have at least one measurable metastatic lesion according to RECIST
version 1.1;
8. Normal organ function:
1. Hematology :Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/mm3); Platelet
count ≥ 100 × 109/L (100000/mm3); Hemoglobin ≥ 90g/L;
2. Kidney:The calculated value of creatinine clearance rate (CrCl) is ≥ 50
mL/min;Normal urine routine, urine protein<2+or 24-hour (h) urine protein
quantification<1.0 g;
3. Liver:Total serum bilirubin (TBiL) ≤ 1.5 × ULN;AST and ALT ≤ 2.5 × ULN; For
subjects with liver metastasis, AST and ALT can be ≤ 5 × ULN;Serum albumin
(ALB) ≥ 30g/L;
4. Normal coagulation function, international standardized ratio (INR) ≤ 1.5 x
ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤
1.5 x ULN;
9. Women of childbearing age must undergo a pregnancy test (serum or urine) with a
negative result within 14 days before enrollment, and voluntarily use appropriate
methods of contraception during the observation period and within 8 weeks after the
last administration of the study drug; For males, surgical sterilization or
agreement to use appropriate methods of contraception during observation and within
8 weeks after the last administration of study medication should be considered;
10. Comply with the scheduled visits, treatment plans, laboratory tests, and other
requirements of the study;
Exclusion Criteria:
1. Local advanced esophageal squamous cell carcinoma that can be curative through
surgery or potentially cured through radiation therapy;
2. Suffering from other malignant tumors within the 5 years prior to enrollment.
Patients with other malignant tumors that have been cured by local treatment, such
as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical
or breast cancer in situ, are not excluded;
3. Active bleeding signs of the lesion are displayed under endoscopy;
4. Currently participating in intervention clinical research treatment, or having
received other research drugs or used research instruments within 4 weeks before the
first administration;
5. Receiving immunotherapy in the past, including immune checkpoint inhibitors (such as
anti-PD-1/L1 antibodies, anti-CTLA-4 antibodies, anti-TIGIT antibodies, anti-LAG3
antibodies, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40
antibodies, etc.), immune cell therapy, or any other treatment targeting the immune
mechanism of tumors;
6. Received systemic non-specific immunomodulatory therapy (such as interleukin,
interferon, thymosin, etc.) within 2 weeks before the first administration;
7. Active autoimmune diseases that require systemic treatment (such as the use of
disease relieving drugs, glucocorticoids, or immunosuppressants) have occurred
within 2 years prior to the first administration.
8. The study is currently undergoing systemic glucocorticoid therapy (excluding local
glucocorticoids through nasal spray, inhalation, or other routes) or any other form
of immunosuppressive therapy within 7 days prior to the first administration; Note:
Physiological doses of glucocorticoids (≤ 10 mg/day of prednisone or equivalent) are
allowed to be used;
9. Clinically significant gastrointestinal obstruction, gastrointestinal perforation,
intra-abdominal abscess, fistula formation, etc. occur within 6 months before the
first administration;
10. Active, uncontrolled, or recurrent inflammatory gastrointestinal diseases (such as
Crohn's disease, ulcerative colitis, radiation enteritis, hemorrhagic enteritis,
chronic diarrhea, etc.);
11. Previous history of myocarditis, cardiomyopathy, and malignant arrhythmia. Unstable
angina, myocardial infarction, congestive heart failure (classified as grade 2 or
above according to the New York Heart Association functional classification) or
vascular disease (such as aortic aneurysm with a risk of rupture) that requires
hospitalization within 12 months prior to the first administration, or other cardiac
damage that may affect the safety evaluation of the investigational drug (such as
poorly controlled arrhythmias, myocardial ischemia);
12. Any arterial thromboembolism events, NCI CTCAE 5.0 grade 3 or above venous
thromboembolism events, transient ischemic attacks, cerebrovascular accidents,
hypertensive crises, or hypertensive encephalopathy occurred within 6 months prior
to the first administration; Currently, there is hypertension and after treatment
with oral antihypertensive drugs, the systolic blood pressure is ≥ 160mmHg or the
diastolic blood pressure is ≥ 100mmHg;
13. Severe infections occurring within 4 weeks prior to the first administration,
including but not limited to comorbidities requiring hospitalization, sepsis, or
severe pneumonia; Active infections that have received systemic anti infective
treatment within 2 weeks prior to the first administration (excluding antiviral
treatment for hepatitis B or C);
14. Subjects with active hepatitis B are required to receive anti hepatitis B virus
treatment during the study treatment; Active hepatitis C subjects (HCV antibody
positive and HCV RNA levels above the detection limit);
15. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation;
16. If the toxicity of previous anti-tumor treatments has not improved, it is defined as
the toxicity has not returned to level 0 or 1 of NCI CTCAE 5.0, or the level
specified in the inclusion/exclusion criteria, except for hair loss;
17. Known to be allergic to any component of any investigational drug; Known medical
history of severe hypersensitivity reactions to other monoclonal antibodies;
18. If a live vaccine or attenuated live vaccine is administered within 30 days prior to
the first administration, or if a live vaccine or attenuated live vaccine is planned
to be administered during the study period, the use of inactivated vaccines is
allowed;
19. Known history of mental illness, drug abuse, alcohol or drug abuse;
20. Pregnant or lactating women;
21. Those who have undergone major surgical procedures or experienced severe trauma
within 30 days prior to the first administration, or those who have planned major
surgical procedures within 30 days after the first administration (as determined by
the investigator); Minor local surgeries were performed within 3 days prior to the
first administration (excluding peripheral venous puncture, central venous
catheterization, and intravenous infusion port implantation);
22. During the screening period, imaging showed significant necrosis and cavities in the
tumor, and the researchers determined that entering the study would pose a risk of
bleeding; Tumors invade important blood vessels and organs; Tumor mediastinal lymph
node metastasis invading the trachea, main bronchus, or at risk of developing
esophagotracheal fistula or esophagopleural fistula;
23. Have a history of severe bleeding tendency or coagulation dysfunction; There are
significant clinically significant bleeding symptoms within one month prior to the
first administration; Patients who have previously or currently require long-term
therapeutic anticoagulation therapy (such as atrial fibrillation patients who meet
CHADS2 score ≥ 2);
24. The researcher believes that there are other potential risks that are not suitable
for participation in this study;
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Tianjin Medical University Cancer Institute and Hospital
Address:
City:
Tianjin
Country:
China
Start date:
October 25, 2024
Completion date:
August 30, 2027
Lead sponsor:
Agency:
Tianjin Medical University Cancer Institute and Hospital
Agency class:
Other
Source:
Tianjin Medical University Cancer Institute and Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06489197
