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

Prior treatment

• Patients treated with an antibody drug conjugate in a curative setting;
• Patients undergoing concurrent treatment for a malignancy or hematologic disorder distinct from the indication for which the ADC is being administered.

Lab values

• 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.

Other

• Patients who did not consent to sample use;
• Presence of another progressive pathology with short-term life-threatening prognosis;
• 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.

• 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.