Health TrialsbyHealthPanel

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

ConditionsAdvanced Breast CancerAdvanced Gastric CancerAdvanced Urothelial CancerAdvanced Non Small Cell Lung Cancer (NSCLC)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUNICANCER

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biological samples collection

    Procedure/Surgery

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

  • questionnaires to collect patient reported outcomes

    Behavioral

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

Treatment groups

400 Participants
are divided into 4 treatment groups
Group A: T-DXd (trastuzumab deruxtecan)Other 2 interventions
Group B: T-DM1 (trastuzumab emtansine)Other 2 interventions
Group C: SG (sacituzumab govitecan)Other 2 interventions
Group D: EV (enfortumab vedotin)Other 2 interventions

Trial outcomes

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)

Time frame
Through study completion, an average of 3 years

Secondary outcomes

1

Additional biomarkers of resistance characterised by histology

Differences in the frequency of molecular aberrations characterised by histologic/proteomic/genomic/transcriptomic analysis between samples of patients progressing on ADC and paired pre-treatment samples (beyond biomarkers of primary outcome)

Time frame
Through study completion, an average of 3 years
2

Biomarkers of ADC outcome

Progression-Free Survival (PFS) defined as the time from start of treatment and radiological progression or death, whichever occurs first. Tumor assessments are made by local investigators as per standard practice (RECIST 1.1.). Patients still alive at the cut-off time without documented progression (including lost to follow-up) will be censored at the time of latest evaluable efficacy assessment.

Time frame
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
3

Biomarkers of ADC outcome

Objective Response Rate (ORR) defined as the proportion of patients with a confirmed complete response (CR) or partial response (PR) assessed by investigators after 6 months of treatment.

Time frame
From first day of cycle 1 (each cycle is 21 to 28 days) to date of 6 months of treatment completion
4

Biomarkers of ADC outcome

Clinical Benefit Rate (CBR) defined as the proportion of patients who had a CR, PR, or stable disease for 6 months or more.

Time frame
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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

UNICANCER

Lead sponsor

Source ClinicalTrials.gov
Apply now