Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT07259226 En recrutement IDF

Titre

International Multicenter Multicohort Open-label Phase II Trial Aiming to Define Optimal Methods for Predicting Response/Resistance to Antibody-drug Conjugates in Patients With Solid Tumors Treated According to Current Standard Indications.

Type

Interventional

Pathologie

Phase

Phase 2

Promoteur

UNICANCER (Voir sur ClinicalTrials)

Date de début

novembre 2025

Date de fin

novembre 2030

Dernière mise à jour

02 décembre 2025

Résumé

International study that will evaluate the association of prespecified biomarkers with resistance to Antibody-drug conjugates (ADCs), a type of targeted cancer treatment currently used in clinical practice for treating different tumor types.

Détail

Voir le détail Over the past five years, antibody-drug conjugates (ADCs) have dramatically improved survival in solid and hematologic malignancies. Among 14 ADCs approved worldwide, nine are now available in Europe, and over 370 others are in clinical development. This expanding landscape indicates that ADCs could soon replace conventional chemotherapy across multiple tumor types. Given this rapid evolution, clinicians will need to select the most suitable ADC for each patient, considering tumor biology, microenvironment (TME) and patient-specific factors. Yet, despite remarkable efficacy, resistance to ADCs eventually arises. Understanding resistance mechanisms is therefore essential to guide therapeutic sequencing and optimize next-generation ADCs. ADCs are complex molecules combining an antibody, a linker, and a cytotoxic payload. Their activity depends on factors such as antigen expression, internalization, linker stability, and payload sensitivity. Resistance can result from altered vascular perfusion, antigen downregulation, defective internalization or trafficking, impaired linker cleavage, drug efflux, or payload target modifications. These multifactorial processes differ from those driving resistance to traditional chemotherapies. Existing preclinical and clinical tools (Patient-Derived Xenograft(PDX)/Cell-line-Derived Xenograft (CDX) models, standard imaging, Immunohistochemistry (IHC), genomic profiling) fail to capture this complexity or predict ADC efficacy and resistance. Furthermore, ADCs often cause significant toxicities-on-target or off-target-affecting the ocular surface, skin, lungs, and peripheral nerves. Patient factors such as age, comorbidities, and weight influence these events. Understanding the determinants of toxicity is critical to maintain quality of life and treatment adherence. The OASIS program aims to identify predictive biomarkers of ADC response and toxicity to enable personalized ADC selection and toxicity prevention. This multicenter study will integrate advanced technologies-digital pathology, liquid biopsy, and Patient-derived organoids (PDOs)-to generate comprehensive biological and clinical data. Using these datasets, a multimodal machine-learning model (OASIS Multiparametric Score) will be developed to predict both efficacy and key toxicities of ADCs. The project will prospectively include patients receiving ADCs in standard practice, with longitudinal tumor and blood sampling to investigate biomarkers of resistance and toxicity. In parallel, preclinical models derived from patient tumors will explore resistance mechanisms and screen ADC sensitivity. A retrospective cohort of patients previously treated with ADCs will first be analyzed to prioritize biomarker candidates based on published data and prior findings. From this, five binary biomarkers will be selected for the primary objective. Combined with prospective data, this retrospective work will expand the translational biobank and support the construction of the OASIS score. Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
CLCC INSTITUT GUSTAVE ROUSSY	Barbara PISTILLI	En recrutement IDF	29/05/2026 19:40:05	Contacter

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

1. Patients must have signed a written informed consent form prior to any trial
specific procedures;

2. Patients must be ≥18 years old;

3. Histologically confirmed or radiologically documented unresectable locally advanced
or metastatic cancer (Breast, Urothelial, Non small Cell Lung or Gastric) with an
indication to receive an Antibody-Drug Conjugate (ADC) approved or accessible
through an early access program;

4. Patients must have at least 2 tumor lesions (primary tumor can be included): at
least one measurable tumor lesion for tumor evaluation according to response
evaluation criteria in solid tumors (RECIST) V1.1 and at least one tumor lesion
other than bone and brain for biopsy;

5. Patients must have a metastatic or locally advanced tumor site easily accessible to
biopsy (with exception of bone and brain metastasis) and must have agreed to perform
pretreatment and post-treatment biopsies; an archival pre-treatment biopsy may be
used if it was collected within one month of enrolment, if no anticancer therapy was
administered after the biopsy and if sufficient material is available for research;

6. Life expectancy must be ≥12 weeks according to the discretion of the investigator;

7. ECOG performance status ≤ 2;

8. Patients must have adequate hematologic and organ function, compatible with ADC
administration, as per drug-specific recommendations;

9. Women of childbearing potential and male patient must agree to use adequate
contraception for the duration of trial participation and up to 7 months after
completing treatment for women and up to 4 months for men;

10. Patients must be affiliated to a social security system (or equivalent);

11. Patients must be willing and able to comply with the protocol for the duration of
the trial;

12. Patients must consent to the use of their collected tumor specimen, as well as,
blood samples as detailed in the protocol for future scientific research, which
includes but is not limited to DNA, RNA, and protein-based biomarker analysis.

Exclusion Criteria:

Critère de non inclusion

1. Patients treated with an antibody drug conjugate in a curative setting;

2. Patients who did not consent to sample use;

3. Presence of another progressive pathology with short-term life-threatening
prognosis;

4. Patients undergoing concurrent treatment for a malignancy or hematologic disorder
distinct from the indication for which the ADC is being administered.

5. Patients with inadequate washout period prior to Cycle 1 Day 1, defined as:

- Whole brain radiation therapy <14 days or stereotactic brain radiation therapy
<7 days.

- Any cytotoxic chemotherapy, investigational agents or other anticancer drug(s)
(including another ADC) from a previous cancer treatment regimen or clinical
study (other than epidermal growth factor receptor tyrosine kinase inhibitor
(EGFR TKI)), <14 days or 5 half-lives, whichever is longer.

- Immune checkpoint inhibitor therapy <21 days.

- Hormonal therapy <21 days.

- Major surgery (excluding placement of vascular access) <28 days.

- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field
of radiation <28 days or palliative radiation therapy <14 days.

6. Female participant who is pregnant, breastfeeding, or planning to become pregnant
while enrolled in this study or within 90 days after the final administration of
study treatment;

7. Person deprived of their liberty or under protective custody or guardianship.

NCT07259226 - International Multicenter Multicohort Open-label Phase II Trial Aiming to Define Optimal Methods for Predicting Response/Resistance to Antibody-drug Conjugates in Patients With Solid Tumors Treated According to Current Standard Indications.

Informations générales
Etablissements
Critères
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