AK112 Combined With Chemotherapy as the First-line Treatment in Advanced Esophageal Squamous Cell Carcinoma Patients

NCT06489197 | Recruiting Phase 2

• 1 other identifier: AK112-IIT-009
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

ESCC; Advanced Esophageal Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate,ORR

  Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.

  6 months

Secondary Outcomes (4)

• Overall survival,OS

  24 months

• Progression free Survival,PFS

  12 months

• Disease Control Rate,DCR

  6 months

• Duration of Response,DoR

  6 months

Other Outcomes (1)

• Incidence of adverse events

  24 months

Study Arms (1)

Experimental arm

EXPERIMENTAL

Ivonescimab combined with albumin paclitaxel and cisplatin

Drug: Ivonescimab combined with albumin paclitaxel and cisplatin

Interventions

Ivonescimab combined with albumin paclitaxel and cisplatin DRUG

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.

Experimental arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

RECRUITING

MeSH Terms

Interventions

Cisplatin

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

Ting Deng, MD

CONTACT

022-23340123; xymcdengting@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2024
• First Posted: July 5, 2024
• Study Start: November 16, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): August 30, 2027
• Last Updated: January 22, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)