Gastric AdenocarcinomaPhase 2NCT06196697
AK104 in Combination With AK112 Plus Chemotherapy(SOX/XELOX) as First-line Treatment for Advanced G/GEJ Cancer
A Phase 2 study testing Cadonilimab, Ivonescimab and XELOX in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by Harbin Medical University at 1 site in China.
Trial summary
The goal of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and anti-tumor activities of cadonilimab in combination with Ivonescimab plus chemotherapy as first-line therapy in adult subjects with HER2 negative、advanced or metastatic gastric (G) or gastroesophageal junction… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma
- What is being tested?
- Cadonilimab, Ivonescimab and XELOX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 10 Apr 2024to Mar 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
- Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
- Imaging examination confirmed unresectable locally advanced or metastatic gastric cancer (GC) or gastroesophageal binding cancer (GEJC), and histopathologically confirmed adenocarcinoma, with at least one measurable tumor lesion (spiral CT or MR scan ≥10mm, gonorrhea The short diameter of sling is ≥15mm, which meets the RECIST 1.1 standard); the lesion that has received radiotherapy is not selected as the target lesion, unless the radiotherapy lesion is the only measurable lesion and is clearly advanced according to imaging judgment, it can be considered as the target lesion;
- Subjects have not received prior systemic therapy for locally advanced or metastatic gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction. For subjects who have received prior neoadjuvant/adjuvant chemotherapy or chemoradiotherapy for curative intent, the time between disease progression and last treatment should be at least 6 months；
- HER2 is negative. HER2 negative is defined as: IHC 0/1+, or IHC 2+ and FISH/ISH negative (HER2: CEP17 ratio <2). FISH can be replaced by locally available and accepted ISH methods (such as DISH);
- The study allowed the inclusion of Subjects with gastric cancer with peritoneal metastasis (imaging results or ascites/abdominal lavage cytology test positive);
- Expected survival period > 3 months;
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- ECOG score: 0-1;
- All acute toxic reactions caused by previous anti-tumor treatment or surgery are relieved to level 0-1 (according to NCI CTCAE version 5.0) or to the level specified in the group/exclusion standard. Except for other toxicicies that researchers such as hair loss, fatigue and hearing damage believe do not pose a safety risk to the subjects;
- Have good organ function (subsists are not allowed to receive blood transfusion or growth factor support treatment within 7 days before the first administration):
- 1) Absolute count of neutrophils ≥1.5×109/L; platelets ≥100×109/L; hemoglobulin ≥90g/L or 5.6mmol/L; 2) Total bilirubin ≤ 1.5 times the upper limit of normal value (ULN); ALT and AST ≤2.5×ULN, for liver metastasis subjects, ALT and AST ≤5×ULN; albumin ≥3.0g/dL (30g/L); 3) serum creatinine ≤1.5 ×ULN or calculated serum creatinine clearance ≥50mL/min (Cockcroft-Gault formula calculation).
- 4) Normal urine routine, or urine protein <2+; if urine protein ≥2+, the 24-hour urine protein quantity must be ≤1g; 5) Normal coagulation function, international standardization ratio (INR) ≤ 1.5×ULN, prothrombin time (PT) and activation partial thrombin time (APTT) ≤ 1.5×ULN; 10. Women of childbearing age must have a negative pregnancy test (βHCG) before starting treatment. Women of childbearing age and men (who have sex with women of childbearing age) must agree to use effective contraceptives continuously during treatment and 6 months after the last therapeutic dose; 11. Subjects signed the informed consent, and able to follow the planned visit, research treatment, laboratory examination and other experimental procedures.
Who cannot join
- known as squamous carcinoma, undifferentiated cancer or other tissue types of gastric cancer, or adenocarcinoma mixed with other tissue types of gastric cancer;
- HER2 positive stomach cancer patients: define IHC 3+, or IHC 2+ and FISH/ISH positive;
- Previously received immune checkpoint inhibitors (such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such as antibodies to ICOS, CD40, CD137, GITR, OX40 targets, etc.) , immune cell therapy and other treatment of any immune mechanism for tumors;
- In the first 14 days of randomization, there is still uncontrollable pleural hydration and ascites after puncture drainage and other treatments. Imaging shows that a small number of or medium chest and ascites patients can be selected for the study;
- Subjects have not received prior systemic therapy for locally advanced or metastatic gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction. For subjects who have received prior neoadjuvant/adjuvant chemotherapy or chemoradiotherapy for curative intent, the time between disease progression and last treatment should be at least 6 months;
- There are significant clinical bleeding symptoms or clear bleeding tendencies within 1 month before the first administration, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, or vasculitis;
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- There are clinically active hemoptysis, active diverticulitis, abdominal abscess, and gastrointestinal obstruction;
- Any other malignant tumors have been diagnosed within 5 years before entering the study, except for skin basal or squamous cell carcinoma, superficial bladder cancer, cervical insitus, intraductal cancer and thyroid papilloma cancer that can be treated locally and have been cured with clear medical records;
- Known active or untreated brain metastases, meningeal metastases, spinal cord compression, or leptomeningeal disease. However, subjects who meet the following requirements and have measurable lesions outside the central nervous system are allowed to enter the group: after treatment, the imaging is stable for at least 4 weeks before the start of the study treatment (if there is no new or expanded brain metastasis), and systemic glucocortic hormone and anticonvulsive drug treatment has been stopped at least 2 weeks;
- Interstitial lung disease, non-infectious pneumonia or uncontrollable systemic diseases (such as diabetes, hypertension, pulmonary fibrosis and acute pneumonia, etc.) are known, and a history of active tuberculosis is known;
- Subjects with active, known or suspected autoimmune disease. But Subjects who are in a stable state and do not require systematic immunosuppressive treatment are allowed, such as type 1 diabetes, hypothyroidism that only needs hormone replacement therapy, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis or hair loss);
- There are clinical symptoms or diseases of the heart that are not well controlled, such as: (1) NYHA level 2 and above cardiac insufficiency or cardiac ultrasound examination: LVEF (left ventricular ejection fraction) <50%; (2) severe/unstable angina pectoris; (3) randomized myocardial infarction within 6 months ; (4) Clinically significant supventricular or ventricular arrhythmia requires treatment or intervention; (5) Symptomatic congestive heart failure; (6) QTc>480 ms (QTc interval is calculated in the Fridericia formula; if QTc is abnormal, it can be separated by 2 minutes. The clock is detected 3 times in a row and takes its average value);
- Received the following treatments or drugs before the first administration:
- Excessive surgery within the first 28 days (tissue biopsy required for diagnosis and peripheral vein puncture central venous catheterization [PICC] / infusion port implantation are allowed);
- Immunosuppressive drugs have been used within the first 14 days, excluding nasal spray and inhalation corticosteroids or systemic steroid hormones at physiological doses (i.e. no more than 10 mg/d prednisone or other corticosteroids of the same physiological dose of the drug);
- Inoculated with live attenuated vaccine within the first 28 days or within 60 days after the study period and the end of the research drug treatment;
- Receive local anti-tumor treatment within the first 28 days (such as radiotherapy or tumor embolization, etc.);
- Received Chinese herbal medicine or Chinese medicine with anti-tumor indications in the first 2 weeks;
- Known allergies or intolerant to test drugs or their excipients; or a known history of severe hypersensitivity reactions to other monoclon antibodies;
- Unable to swallow, malabsorption syndrome, or uncontrollable nausea, vomiting, diarrhea or other gastrointestinal diseases that seriously affect drug use and absorption;
- Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis (hepatitis B, defined as HBV-DNA≥500 IU/ml; hepatitis C, defined as anti-HCV positive and HCV RNA higher than analysis The lower limit of detection of the method) or combined with hepatitis B and hepatitis C;
- Subjects who cannot comply with the test plan or cannot cooperate with the follow-up;
- Any conditions that, in the investigator's opinion, may put subjects treated with the study drug at risks, or interfere with the evaluation of study drug or subject safety, or the interpretation of results.
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
Harbin Medical University Hospital
Harbin
Yanqiao Zhang, phD
About this study
Official title: A Phase II, Single Arm, Single Center Study of Cadonilimab(AK104) in Combination With Ivonescimab(AK112) Plus Chemotherapy(SOX/XELOX) as First-line Treatment for Advanced Gastric (G) or Gastroesophageal Junction (GEJ) Cancer
The goal of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and anti-tumor activities of cadonilimab in combination with Ivonescimab plus chemotherapy as first-line therapy in adult subjects with HER2 negative、advanced or metastatic gastric (G) or gastroesophageal junction (GEJ) cancer.
Read the detailed description
The study consists of a dose escalation and expansion phase to determine the recommended Phase 2 dose (RP2D) for AK104 in combination with AK112 and SOX/XELOX, and a dose confirmation phase which will further characterize the treatment of AK104 in combination at the RP2D.
- Being tested
- Cadonilimab, Ivonescimab, XELOX, SOX
- Keywords
- first-line treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CadonilimabBiological
Also called AK104
Subjects will receive AK104 by intravenous administration
IvonescimabBiological
Also called AK112
Subjects will receive AK112 by intravenous administration
XELOXDrug
Also called oxaliplatin and capecitabine
Subjects will receive AK104 and AK112 in combination with XELOX(oxaliplatin and capecitabine)
SOXDrug
Also called oxaliplatin and Tegafur
Subjects will receive AK104 and AK112 in combination withSOX(oxaliplatin and Tegafur)
| Study group | Role | What they receive |
|---|---|---|
| AK104+AK112+SOX/XELOX | Experimental | Biological: Cadonilimab (AK104) 10mg/kg or 15mg/kg or 6mg/kg Q6W iv D8 (dose choosing depends on the outcome of the dose climb stage) Biological: Ivonescimab (AK112): 20mg/kg Q3W iv D1 Drug:SOX or XELOX SOX: Oxaliplatin (130 mg/m2 intravenous infusion for 2-6 hours on Day 1, Q3W,up to 6 cycles)+ Tegafur (40 mg/m2, p.o., Bid, Q3W, for day 1 to day 14 per cycle) XELOX: Oxaliplatin (130 mg/m2 intravenous infusion for 2-6 hours on Day 1, Q3W,up to 6 cycles)+Capecitabine(1000 mg/m2, p.o., Bid, Q3W, for day 1 to day 14 per cycle) Receives: Biological: Cadonilimab; Biological: Ivonescimab; Drug: XELOX; Drug: SOX |
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 (5)
Progression free Survival
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: 1 year
Overall survival
Defined as the time between signing the informed consent form to death due to various causes.
Measured: 2 years
Disease Control Rate
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
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
Incidence of adverse events
Use NCI-CTCAE version 5.0 for classification and grading.
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 posted9 Jan 2024
- Study start10 Apr 2024
- Primary completionJan 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric AdenocarcinomaStudies of the same condition, open and under way.
- 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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Harbin Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanqiao Zhang, Harbin Medical University
- Investigators
- yanqiao zhang, phD, Principal investigator, Harbin Medical University Cancer Hosptital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06196697
- Sponsor's protocol ID
- AK104-IIT-041
- Status last verified
- Jun 2024
- First submitted
- 25 Dec 2023
- Last updated
- 27 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single Arm, Single Center Study of Cadonilimab(AK104) in Combination With Ivonescimab(AK112) Plus Chemotherapy(SOX/XELOX) as First-line Treatment for Advanced Gastric (G) or Gastroesophageal Junction (GEJ) Cancer
- ClinicalTrials.gov ID
- NCT06196697
- Acronym / sponsor ID
- AK104-IIT-041
- Keywords
- first-line treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Harbin Medical UniversityUniversity, hospital or other
- Study start
- 10 Apr 2024 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 9 Jan 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.
The goal of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and anti-tumor activities of cadonilimab in combination with Ivonescimab plus chemotherapy as first-line therapy in adult subjects with HER2 negative、advanced or metastatic gastric (G) or gastroesophageal junction (GEJ) cancer.
Detailed description
The study consists of a dose escalation and expansion phase to determine the recommended Phase 2 dose (RP2D) for AK104 in combination with AK112 and SOX/XELOX, and a dose confirmation phase which will further characterize the treatment of AK104 in combination at the RP2D.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AK104+AK112+SOX/XELOX | Experimental | Biological: Cadonilimab, Biological: Ivonescimab, Drug: XELOX, Drug: SOXBiological: Cadonilimab (AK104) 10mg/kg or 15mg/kg or 6mg/kg Q6W iv D8 (dose choosing depends on the outcome of the dose climb stage) Biological: Ivonescimab (AK112): 20mg/kg Q3W iv D1 Drug:SOX or XELOX SOX: Oxaliplatin (130 mg/m2 intravenous infusion for 2-6 hours on Day 1, Q3W,up to 6 cycles)+ Tegafur (40 mg/m2, p.o., Bid, Q3W, for day 1 to day 14 per cycle) XELOX: Oxaliplatin (130 mg/m2 intravenous infusion for 2-6 hours on Day 1, Q3W,up to 6 cycles)+Capecitabine(1000 mg/m2, p.o., Bid, Q3W, for day 1 to day 14 per cycle) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
- Imaging examination confirmed unresectable locally advanced or metastatic gastric cancer (GC) or gastroesophageal binding cancer (GEJC), and histopathologically confirmed adenocarcinoma, with at least one measurable tumor lesion (spiral CT or MR scan ≥10mm, gonorrhea The short diameter of sling is ≥15mm, which meets the RECIST 1.1 standard); the lesion that has received radiotherapy is not selected as the target lesion, unless the radiotherapy lesion is the only measurable lesion and is clearly advanced according to imaging judgment, it can be considered as the target lesion;
- Subjects have not received prior systemic therapy for locally advanced or metastatic gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction. For subjects who have received prior neoadjuvant/adjuvant chemotherapy or chemoradiotherapy for curative intent, the time between disease progression and last treatment should be at least 6 months；
- HER2 is negative. HER2 negative is defined as: IHC 0/1+, or IHC 2+ and FISH/ISH negative (HER2: CEP17 ratio <2). FISH can be replaced by locally available and accepted ISH methods (such as DISH);
- The study allowed the inclusion of Subjects with gastric cancer with peritoneal metastasis (imaging results or ascites/abdominal lavage cytology test positive);
Key exclusion criteria (23 listed)
- known as squamous carcinoma, undifferentiated cancer or other tissue types of gastric cancer, or adenocarcinoma mixed with other tissue types of gastric cancer;
- HER2 positive stomach cancer patients: define IHC 3+, or IHC 2+ and FISH/ISH positive;
- Previously received immune checkpoint inhibitors (such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such as antibodies to ICOS, CD40, CD137, GITR, OX40 targets, etc.) , immune cell therapy and other treatment of any immune mechanism for tumors;
- In the first 14 days of randomization, there is still uncontrollable pleural hydration and ascites after puncture drainage and other treatments. Imaging shows that a small number of or medium chest and ascites patients can be selected for the study;
- Subjects have not received prior systemic therapy for locally advanced or metastatic gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction. For subjects who have received prior neoadjuvant/adjuvant chemotherapy or chemoradiotherapy for curative intent, the time between disease progression and last treatment should be at least 6 months;
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 |
|---|---|---|
| CadonilimabAlso: AK104Subjects will receive AK104 by intravenous administration | Biological | AK104+AK112+SOX/XELOX |
| IvonescimabAlso: AK112Subjects will receive AK112 by intravenous administration | Biological | AK104+AK112+SOX/XELOX |
| XELOXAlso: oxaliplatin and capecitabineSubjects will receive AK104 and AK112 in combination with XELOX(oxaliplatin and capecitabine) | Drug | AK104+AK112+SOX/XELOX |
| SOXAlso: oxaliplatin and TegafurSubjects will receive AK104 and AK112 in combination withSOX(oxaliplatin and Tegafur) | Drug | AK104+AK112+SOX/XELOX |
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.
5 secondary outcomes
Progression free Survival
Time frame: 1 year
Overall survival
Time frame: 2 years
Disease Control Rate
Time frame: 6 months
Duration of Response
Time frame: 6 months
Incidence of adverse events
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 27 Jun 2024.
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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.
yanqiao zhang, phD principal investigator
Harbin Medical University Cancer Hosptital
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 Cadonilimab, Ivonescimab and XELOX in people with Gastric Adenocarcinoma and Gastroesophageal Junction Adenocarcinoma, run by Harbin Medical University 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 11 inclusion and 23 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 27 Jun 2024. 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 yanqiao zhang, phD (+86 138 4512 0210, yanqiaozhang@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 27 Jun 2024.