Optimal Methods to Characterize ADC Resistance in Solid Tumors and Identify Clinically Useful Biomarkers

NCT07259226 | Recruiting Phase 2

• 2 other identifiers: UC-TRA-2507ID RCB 2025-A01462-47
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Breast Cancer; Advanced Gastric Cancer; Advanced Urothelial Cancer; Advanced Non Small Cell Lung Cancer (NSCLC)

Keywords

ADC; resistance

Outcome Measures

Primary Outcomes (1)

• Biomarkers of resistance to ADC

  Resistance is defined by differences in the frequency (higher or lower) of molecular aberrations detected between paired baseline samples and progression samples (i.e., samples collected at the time of disease progression under ADC treatment)

  Through study completion, an average of 3 years

Secondary Outcomes (12)

• Additional biomarkers of resistance characterised by histology

  Through study completion, an average of 3 years

• Biomarkers of ADC outcome

  From first day of cycle 1 (each cycle is 21 to 28 days) to date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

• Biomarkers of ADC outcome

  From first day of cycle 1 (each cycle is 21 to 28 days) to date of 6 months of treatment completion

• Biomarkers of ADC outcome

  From first day of cycle 1 (each cycle is 21 to 28 days) to date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

• Biomarkers of resistance to ADC

  From first day of cycle 1 (each cycle is 21 to 28 days) to date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Study Arms (4)

T-DXd (trastuzumab deruxtecan)

OTHER

Standard of care T-DXd indication

Procedure: Biological samples collection; Behavioral: questionnaires to collect patient reported outcomes

T-DM1 (trastuzumab emtansine)

OTHER

Standard of care T-DM1 indication

Procedure: Biological samples collection; Behavioral: questionnaires to collect patient reported outcomes

SG (sacituzumab govitecan)

OTHER

Standard of care SG indication

Procedure: Biological samples collection; Behavioral: questionnaires to collect patient reported outcomes

EV (enfortumab vedotin)

OTHER

Standard of care EV indication

Procedure: Biological samples collection; Behavioral: questionnaires to collect patient reported outcomes

Interventions

Biological samples collection PROCEDURE

Biological samples collection (tumor tissue, blood, sputum) before initiation of treatment, during treatment, and at treatment discontinuation.

Also known as: Blood sample collection, Sputum sample collection, Tumor tissue sample collection

EV (enfortumab vedotin); SG (sacituzumab govitecan); T-DM1 (trastuzumab emtansine); T-DXd (trastuzumab deruxtecan)

questionnaires to collect patient reported outcomes BEHAVIORAL

QLQ-C30, QLQ-FA12, HADS, EQ-5D 5L

EV (enfortumab vedotin); SG (sacituzumab govitecan); T-DM1 (trastuzumab emtansine); T-DXd (trastuzumab deruxtecan)

Eligibility Criteria

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

You may qualify if:

• Patients must have signed a written informed consent form prior to any trial specific procedures;
• Patients must be ≥18 years old;
• 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;
• 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;
• 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;
• Life expectancy must be ≥12 weeks according to the discretion of the investigator;
• ECOG performance status ≤ 2;
• Patients must have adequate hematologic and organ function, compatible with ADC administration, as per drug-specific recommendations;
• 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;
• Patients must be affiliated to a social security system (or equivalent);
• Patients must be willing and able to comply with the protocol for the duration of the trial;
• 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.

You may not qualify if:

• Patients treated with an antibody drug conjugate in a curative setting;
• Patients who did not consent to sample use;
• Presence of another progressive pathology with short-term life-threatening prognosis;
• Patients undergoing concurrent treatment for a malignancy or hematologic disorder distinct from the indication for which the ADC is being administered.
• 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.
• 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;
• Person deprived of their liberty or under protective custody or guardianship.

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (1)

Gustave Roussy Cancer Center

Villejuif, 94805, France

RECRUITING

Study Officials

• Barbara Pistilli, MD, PhD

  Gustave Roussy Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marjorie Mauduit

CONTACT

+33 6 30481792; m-mauduit@unicancer.fr

Jérôme Lemonnier

CONTACT

j-lemonnier@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2025
• First Posted: December 2, 2025
• Study Start: November 14, 2025
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): November 1, 2030
• Last Updated: December 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)