ESCCPhase 2NCT06489197
AK112 Combined With Chemotherapy as the First-line Treatment in Advanced Esophageal Squamous Cell Carcinoma Patients
A Phase 2 study testing Ivonescimab combined with albumin paclitaxel and cisplatin in people with ESCC and Advanced Esophageal Squamous Cell Carcinoma, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- ESCC, Advanced Esophageal Squamous Cell Carcinoma
- What is being tested?
- Ivonescimab combined with albumin paclitaxel and cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 16 Nov 2024to 30 Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed the informed consent；
- Male or female patients ≥18 and ≤ 75 years old;
- ECOG physical status score is 0 or 1;
- Patients with non resectable or metastatic advanced ESCC confirmed by pathological ocytological examination;
- No previous systemic treatment;
- Expected survival time ≥ 3 months;
Show all 14Show fewer
- Patients must have at least one measurable metastatic lesion according to RECIST version 1.1;
- Normal organ function:
- Hematology :Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/mm3); Platelet count ≥ 100 × 109/L (100000/mm3); Hemoglobin ≥ 90g/L;
- 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;
- 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;
- Normal coagulation function, international standardized ratio (INR) ≤ 1.5 x ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN;
- 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;
- Comply with the scheduled visits, treatment plans, laboratory tests, and other requirements of the study;
Who cannot join
- Local advanced esophageal squamous cell carcinoma that can be curative through surgery or potentially cured through radiation therapy;
- 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;
- Active bleeding signs of the lesion are displayed under endoscopy;
- Currently participating in intervention clinical research treatment, or having received other research drugs or used research instruments within 4 weeks before the first administration;
- 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;
- Received systemic non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, etc.) within 2 weeks before the first administration;
Show all 24Show fewer
- 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.
- 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;
- Clinically significant gastrointestinal obstruction, gastrointestinal perforation, intra-abdominal abscess, fistula formation, etc. occur within 6 months before the first administration;
- Active, uncontrolled, or recurrent inflammatory gastrointestinal diseases (such as Crohn's disease, ulcerative colitis, radiation enteritis, hemorrhagic enteritis, chronic diarrhea, etc.);
- 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);
- 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;
- 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);
- 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);
- Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
- 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;
- Known to be allergic to any component of any investigational drug; Known medical history of severe hypersensitivity reactions to other monoclonal antibodies;
- 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;
- Known history of mental illness, drug abuse, alcohol or drug abuse;
- Pregnant or lactating women;
- 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);
- 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;
- 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);
- The researcher believes that there are other potential risks that are not suitable for participation in this study;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality
Ting Deng, MD, 022-23340123 ext. 1053, xymcdengting@126.com
About this study
Official title: Ivonescimab(AK112) Combined With Chemotherapy as the First-line Treatment in Patients With Advanced Esophageal Squamous Cell Carcinoma (ESCC): A Single Arm , Phase II Trial
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.
Read the 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.
- Conditions
- ESCC, Advanced Esophageal Squamous Cell Carcinoma
- Being tested
- Ivonescimab combined with albumin paclitaxel and cisplatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivonescimab combined with albumin paclitaxel and cisplatinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | Ivonescimab combined with albumin paclitaxel and cisplatin Receives: Drug: Ivonescimab combined with albumin paclitaxel and cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate,ORR
Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.
Measured: 6 months
Secondary outcomes (4)
Overall survival,OS
Defined as the time between signing the informed consent form to death due to various causes.
Measured: 24 months
Progression free Survival,PFS
Defined as the time between signing the informed consent form to the disease progression (according to RECIST v1.1 criteria) or death due to any cause.
Measured: 12 months
Disease Control Rate,DCR
Defined as the proportion of patients who achieved complete response (CR), partial response (PR), and stable disease (SD) according to RECIST v1.1.
Measured: 6 months
Duration of Response,DoR
Defined as the time from response(when CR or PR is first diagnosed) to disease progression or death due to any cause.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2024
- Study start16 Nov 2024
- Primary completion30 Oct 2026 (estimated)
- Study completion30 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ESCCStudies of the same condition, open and under way.
- More trials run by Tianjin Medical University Cancer Institute and HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06489197
- Sponsor's protocol ID
- AK112-IIT-009
- Status last verified
- Jun 2024
- First submitted
- 28 Jun 2024
- Last updated
- 22 Jan 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ivonescimab(AK112) Combined With Chemotherapy as the First-line Treatment in Patients With Advanced Esophageal Squamous Cell Carcinoma (ESCC): A Single Arm , Phase II Trial
- ClinicalTrials.gov ID
- NCT06489197
- Acronym / sponsor ID
- AK112-IIT-009
- Conditions
- ESCC, Advanced Esophageal Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Study start
- 16 Nov 2024 (actual)
- Primary completion
- 30 Oct 2026 (estimated)
- Study completion
- 30 Aug 2027 (estimated)
- First posted
- 5 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Drug: Ivonescimab combined with albumin paclitaxel and cisplatinIvonescimab combined with albumin paclitaxel and cisplatin |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Signed the informed consent；
- Male or female patients ≥18 and ≤ 75 years old;
- ECOG physical status score is 0 or 1;
- Patients with non resectable or metastatic advanced ESCC confirmed by pathological ocytological examination;
- No previous systemic treatment;
Key exclusion criteria (24 listed)
- Local advanced esophageal squamous cell carcinoma that can be curative through surgery or potentially cured through radiation therapy;
- 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;
- Active bleeding signs of the lesion are displayed under endoscopy;
- Currently participating in intervention clinical research treatment, or having received other research drugs or used research instruments within 4 weeks before the first administration;
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ivonescimab combined with albumin paclitaxel and cisplatinIvonescimab (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. | Drug | Experimental arm |
Primary outcome
Objective Response Rate,ORR
Time frame: 6 months
Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.
4 secondary outcomes
Overall survival,OS
Time frame: 24 months
Progression free Survival,PFS
Time frame: 12 months
Disease Control Rate,DCR
Time frame: 6 months
Duration of Response,DoR
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2025.
- Individual participant dataSharing planned: No
Related trials for ESCC
Not yet recruitingObservational study
Standardized Management of Esophageal Fistula in Esophageal Squamous Cell Carcinoma
Esophageal Squamous Cell Carcinoma (ESCC), Esophageal Fistula
Active, not recruiting
Clinical Application of an AI-based Dissection Trajectory Prediction System (ADTPS) in Endoscopic Submucosal Dissection
Esophageal Squamous Cell Carcinoma (ESCC), High-Grade Intraepithelial Neoplasia
RecruitingPhase 1
A Study of [225Ac]Ac-AKY-2519 in Patients With B7-H3 Expressing Solid Tumors
NSCLC, NSCLC (Advanced Non-small Cell Lung Cancer)
RecruitingPhase 2
QL1706 Plus Celecoxib in Advanced Esophageal Squamous Cell Carcinoma
Esophageal Squamous Cell Carcinoma
RecruitingPhase 1/2
CR-002 in Adult Participants With Locally Advanced or Metastatic Solid Tumors
Head and Neck Squamous Cell Carcinoma (HNSCC) - Recurrent/Metastatic (R/M), Gastric/GEJ
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ivonescimab combined with albumin paclitaxel and cisplatin in people with ESCC and Advanced Esophageal Squamous Cell Carcinoma, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ting Deng, MD (022-23340123 ext. 1053, xymcdengting@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate,ORR (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2025.