Perioperative Cadonilimab (AK104) in Locally Advanced MSI-H/dMMR Gastric or Gastroesophageal Junction and Colorectal Adenocarcinoma
A Multicenter, Open-Label, Phase II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 in the Perioperative Treatment of Locally Advanced Microsatellite Instability/Mismatch Repair Protein-Deficient Gastric and Colorectal Adenocarcinoma
The goal of this phase 2 clinical trial is to learn whether a medicine called cadonilimab (AK104) can safely and effectively treat certain stomach and colon cancers when it is given before and after surgery. Cadonilimab is a type of immunotherapy that targets PD-1 and CTLA-4. The study includes two groups of participants:
- Cohort 1: people with locally advanced gastric or gastroesophageal junction adenocarcinoma
- Cohort 2: people with locally advanced colorectal adenocarcinoma
All participants will have a tumor with a genetic change called MSI-H or dMMR and will be able to have surgery.The main question this study aims to answer is:• How many participants have no signs of cancer left in the tissue removed during surgery (pathologic complete response) after receiving cadonilimab?Other questions the study will look at include:
- How long participants live overall and without the cancer coming back
- How many participants have a major but not complete response in the removed tumor tissue
- What side effects happen with cadonilimab before and after surgery
In this multicenter, single-arm trial, all participants will:
- Receive cadonilimab by intravenous infusion every 3 weeks for 3 cycles before surgery
- Have surgery to remove the tumor
- May continue cadonilimab once a month for up to 6 months after surgery, or stop sooner if the cancer gets worse or side effects are not tolerable
- Have regular clinic visits, blood tests, and scans so researchers can monitor their health and how the cancer responds to treatment
The study uses a two-stage design to decide whether cadonilimab shows enough benefit to justify further research.
Studie Overzicht
Toestand
Toestand
Conditie
Conditie
Interventie / Behandeling
Interventie / Behandeling
Studietype
Studietype
Inschrijving (Geschat)
Inschrijving
Fase
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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Beijing Municipality
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Beijing, Beijing Municipality, China, 100142
- Peking University Cancer Hospital & Institute
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Deelname Criteria
Geschiktheidscriteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Written and signed informed consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
- The estimated life expectancy of ≥3 months.
- Confirmed MSI-H/dMMR status by the central laboratory.
- For cohort 1, histologically or cytologically documented locally advanced gastric carcinoma(cT3-T4a, Nx, M0). For cohort 2, histologically or cytologically documented locally advanced colorectal cancer(cT3-T4a, Nx, M0).
- Haven't received any chemotherapy or radiotherapy.
- Adequate organ function.
- All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
Exclusion Criteria:
- Is currently participating in a study of an investigational agent or using an investigational device;
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment;
- Has undergone major surgery within 30 days of Study Day 1;
- Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases;
- Has carcinomatous meningitis;
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment NOTE: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study;
- Has an active infection requiring systemic therapy;
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected);
- History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months prior to day 1 of study treatment;
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator;
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study;
- Has received a live virus vaccine within 30 days of the planned first dose of study therapy;
- Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment;
- Has any concurrent medical condition that, in the opinion of the Investigator, would complicate or compromise compliance with the study or the well-being of the subject.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Aantal wapens
Wapens en interventies
Deelnemersgroep / ArmDeelnemersgroep / Arm |
Interventie / BehandelingInterventie / Behandeling |
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Experimenteel: AK104 for Gastric/GEJ and Colorectal Adenocarcinoma
Participants with locally advanced MSI-H or dMMR gastric/GEJ and colorectal adenocarcinoma will receive neoadjuvant AK104 10 mg/kg by intravenous infusion every 3 weeks for 3 cycles. Surgery will be performed 3-6 weeks after completion of neoadjuvant treatment. After surgery, participants will receive postoperative AK104 6 mg/kg by intravenous infusion once monthly for up to 6 months or until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. |
Participants will receive AK104 10 mg/kg by intravenous infusion every 3 weeks for 3 cycles before surgery. Surgery will be performed 3-6 weeks after completion of neoadjuvant treatment. After surgery, participants will receive AK104 6 mg/kg by intravenous infusion once monthly for up to 6 months or until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria are met. For participants with gastric or gastroesophageal junction adenocarcinoma, radical gastrectomy or gastroesophageal junction resection with appropriate lymphadenectomy will be performed according to tumor location and institutional standards. For participants with colorectal adenocarcinoma, radical colorectal resection with regional lymphadenectomy, will be performed according to tumor location and institutional standards. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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The rate of pathologic complete response
Tijdsspanne: After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
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Proportion of patients with locally advanced dMMR/MSI-H gastric or colorectal adenocarcinoma who receive neoadjuvant AK104 monotherapy and undergo surgery, who achieve a pathologic complete response based on blinded pathologic assessment by two pathologists with an associate senior professional title or higher. |
After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
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Secundaire uitkomstmaten
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Major Pathologic Response (MPR) rate
Tijdsspanne: After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
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Proportion of participants who achieve a major pathologic response, defined as residual viable tumor (RVT) ≤10% in the resected primary tumor specimen. |
After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
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R0 resection rate
Tijdsspanne: At surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
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Proportion of participants who achieve an R0 resection, defined as microscopically margin-negative resection with no residual tumor at the resection margins. |
At surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
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Event-free survival (EFS)
Tijdsspanne: From the first dose of study treatment to the first EFS event or censoring, up to 5 years; EFS rates assessed at 12, 24, and 36 months.
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From the first dose of study treatment to the first EFS event or censoring, up to 5 years; EFS rates assessed at 12, 24, and 36 months.
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Disease-Free Survival (DFS)
Tijdsspanne: From the first dose of study treatment to the first DFS event or censoring, up to 5 years; DFS rates assessed at 12, 24, and 36 months.
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From the first dose of study treatment to the first DFS event or censoring, up to 5 years; DFS rates assessed at 12, 24, and 36 months.
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Overall survival (OS)
Tijdsspanne: From the first dose of study treatment to the first OS event or censoring, up to 5 years; OS rates assessed at 12, 24, and 36 months.
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From the first dose of study treatment to the first OS event or censoring, up to 5 years; OS rates assessed at 12, 24, and 36 months.
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Postoperative Complication Within 30 Days
Tijdsspanne: From the date of surgery through 30 days after surgery.
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From the date of surgery through 30 days after surgery.
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Adverse Events (AEs)
Tijdsspanne: From first dose to 30 days after the last study-treatment dose or start of other anticancer therapy, whichever occurs first; immune-related AEs through 90 days after the last AK104 dose, regardless of subsequent anticancer therapy.
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From first dose to 30 days after the last study-treatment dose or start of other anticancer therapy, whichever occurs first; immune-related AEs through 90 days after the last AK104 dose, regardless of subsequent anticancer therapy.
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Completion Rate of Postoperative Adjuvant Therapy
Tijdsspanne: From the first postoperative adjuvant dose to completion or discontinuation of the 6 planned cycles (each cycle is 28 days; planned duration is 24 weeks).
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From the first postoperative adjuvant dose to completion or discontinuation of the 6 planned cycles (each cycle is 28 days; planned duration is 24 weeks).
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Medewerkers en onderzoekers
Sponsor
Sponsor
Onderzoekers
Onderzoekers
- Hoofdonderzoeker: Jiafu Ji, Peking University Cancer Hospital & Institute
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Studie start
Primaire voltooiing (Geschat)
Primaire voltooiing
Studie voltooiing (Geschat)
Studie voltooiing
Studieregistratiedata
Eerst ingediend
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Eerst geplaatst
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update geplaatst
Laatste update ingediend die voldeed aan QC-criteria
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
Andere studie-ID-nummers
- AK104-IIT-002
Plan Individuele Deelnemersgegevens (IPD)
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Informatie over medicijnen en apparaten, studiedocumenten
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