KRAS G12D-specific Immune Effector Cells Targeting KRAS G12D-positive Solid Tumors
KRAS G12D-specific Engineered Immune Effectors (EIE) Targeting High-risk Tumors With KRAS G12D Mutation
The purpose of this study is to assess the feasibility, safety and efficacy of KRAS G12D-specific engineered immune effector (EIE) therapy in patients with advanced, KRAS G12D-positive malignancies. Another goal of the study is to characterize the function, expansion and persistence of KRAS G12D-specific effector cells in treated patients.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
Important Regulatory Notice:
This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.
ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.
KRAS G12D mutation is one of the most frequent oncogenic drivers in human malignancies including pancreatic ductal adenocarcinoma, colorectal cancer, non-small cell lung cancer and other advanced solid tumors. Patients with metastatic KRAS G12D mutated tumors generally have poor prognosis; after failure of standard chemotherapy, targeted therapy and checkpoint immunotherapy, effective salvage treatment options remain very limited, and overall survival is unsatisfactory. Conventional chemotherapy and existing targeted agents cannot achieve durable tumor control for large proportions of these patients.
The somatic KRAS G12D neoantigen is tumor-specific, absent in normal human tissues, and critical for maintaining malignant phenotypes, which makes it an attractive target for adoptive cell immunotherapy. This trial investigates autologous KRAS G12D-specific EIE therapy. Peripheral blood mononuclear cells (PBMCs) will be collected via leukapheresis and stimulated with autologous dendritic cells primed with KRAS G12D-specific immunogenic peptides. Manufactured EIE products will be phenotypically profiled for CD8+, CD4+ and CD56+ lymphocyte subsets together with antigen specific reactivity. This phase 1/2 study aims to evaluate safety, manufacturing feasibility and preliminary anti-tumor efficacy of autologous KRAS G12D-specific EIEs in subjects with KRAS G12D-positive tumors.
Type d'étude
Inscription (Estimé)
Phase
- N'est pas applicable
Contacts et emplacements
Coordonnées de l'étude
- Nom: Lung-Ji Chang, PhD
- Numéro de téléphone: +86 13671121909
- E-mail: c@mkgimi.com
Lieux d'étude
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Guangdong
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Shenzhen, Guangdong, Chine, 518000
- Shenzhen Geno-immune Medical Institute
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Contact:
- Lung-Ji Chang, PhD
- Numéro de téléphone: +86 13671121909
- E-mail: c@mkgimi.com
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-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Abilities to understand and the willingness to provide written informed consent;
- ≥ 18 and ≤ 75 years old;
- Histologically confirmed recurrent, refractory or metastatic advanced malignancies with documented KRAS G12D somatic mutation and measurable lesions by RECIST v1.1; patients have progressed after at least one line of standard of care systemic therapy for their malignancy. At time of leukapheresis, patients are either off dexamethasone or receiving dexamethasone ≤ 4 mg/day;
- ECOG performance status 0-2 (or Karnofsky performance score ≥ 60);
- Life expectancy >3 months;
- Satisfactory bone marrow, liver and kidney functions as defined by the following: absolute neutrophile count ≥ 1500/mm^3; hemoglobin > 10 g/dL; platelets > 100000 /mm^3; Bilirubin < 1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5×ULN; creatinine < 1.5×ULN;
- Peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;
- Satisfactory heart functions;
- Must be willing to follow the instructions of doctors;
- Women of reproductive potential (between 15 and 49 years old) must have a negative pregnancy test within 7 days of study start. Male and female patients of reproductive potential must agree to use birth control during the study and 3 months post study.
Exclusion Criteria:
- Receipt of KRAS G12D based therapy within 8 weeks prior to study entry;
- HIV positive;
- Tuberculosis infection not under control;
- History of autoimmune disease, or other diseases requiring long-term administration of steroids or immunosuppressive therapies;
- History of allergic disease, or allergy to immune cells or study product;
- Patients already actively enrolled in other immune cell clinical study;
- Presence of untreated or actively progressing central nervous system metastases not locally controlled;
- Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: KRAS G12D-EIEs
Autologous KRAS G12D-specific engineered immune effectors (EIEs) |
1 to 2 infusions, once a week, for 1x10^5~1x10^7 EIEs/kg via intravenous injection each time |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Percentage of adverse effects after KRAS G12D-EIE injection
Délai: up to one month
|
To assess the safety of autologous KRAS G12D-EIEs in vivo. The percentage of patients who have adverse effects will be evaluated by using the NCI CTCAE V4.0 criteria. |
up to one month
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Rate of successful KRAS G12D-EIE generation
Délai: up to one month
|
The percentage of successful KRAS G12D-EIE generation, which are derived from subjects and pass the safety test after standard culture procedures, viable for at least one preparation, will be evaluated. |
up to one month
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|
Ability of KRAS G12D-EIE cells to induce cancer-specific reactions
Délai: : after 1 month from KRAS G12D-EIE cell infusion until 24 months after infusion
|
ELISPOT measurement of target-specific T cells in blood sample |
: after 1 month from KRAS G12D-EIE cell infusion until 24 months after infusion
|
|
Ability of KRAS G12D-EIE cells inducing tumor reduction
Délai: after 1 month from KRAS G12D-EIE cell infusion until 24 months after infusion
|
Objective response (complete response (CR) + partial response (PR)) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. CR is disappearance of all target lesions. Any pathological lesions (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
after 1 month from KRAS G12D-EIE cell infusion until 24 months after infusion
|
Collaborateurs et enquêteurs
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Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Autres numéros d'identification d'étude
- GIMI-IRB-26004
Informations sur les médicaments et les dispositifs, documents d'étude
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Étudie un produit d'appareil réglementé par la FDA américaine
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