Protein-Matched ADC or PDC Umbrella Trial in Advanced Pancreatic and Breast Cancer

ConditionsAdvanced or Metastatic Pancreatic Adenocarcinoma Advanced or Metastatic Breast Cancer (BC)

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-75

SponsorFudan University

About this trial

To evaluate the clinical efficacy (objective response rate, ORR) of mass spectrometry-based absolute quantification-guided selection and matching of ADC/PDC therapy in patients with locally advanced or metastatic pancreatic cancer/breast cancer, and to explore a quantitative threshold-based stratification strategy for identifying a "hidden benefit population

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male or female patients aged ≥18 years and ≤75 years at the time of informed consent.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Life expectancy of ≥3 months, as assessed by the investigator.

Histologically confirmed recurrent (unresectable) or metastatic advanced pancreatic cancer or breast cancer.

Disqualifiers

Known history of severe hypersensitivity to the investigational drug substance, any excipients contained in the study drug formulation, or other monoclonal antibodies/peptides.

Leptomeningeal metastases or active brain parenchymal metastases. Patients with clinically stable brain parenchymal metastases may be eligible, including those with asymptomatic brain metastases that have not received prior local therapy; or patients who have previously received treatment for CNS metastases (radiotherapy or surgery), provided that imaging-confirmed disease stability has been maintained for at least 4 weeks and symptomatic treatment (including corticosteroids and mannitol) has been discontinued for more than 2 weeks.

Presence of or history of other malignancies, with the following exceptions: cured basal cell carcinoma or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, papillary thyroid carcinoma, ductal carcinoma in situ of the breast, or any other malignancy with disease-free survival exceeding 3 years.

Uncontrolled concurrent illness, including but not limited to: persistent or active infection, uncontrolled or clinically significant cardiovascular disease, severe chronic gastrointestinal disease associated with diarrhea, or any psychiatric illness or social situation that, in the investigator's judgment, would limit compliance with study requirements, significantly increase the risk of adverse events, or impair the ability to provide written informed consent.

Trial design

Design model

Parallel

Treatments tested in this trial

Trastuzumab emtansine (T-DM1)
Drug
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) consisting of the humanized anti-HER2 monoclonal antibody trastuzumab covalently linked to the cytotoxic maytansinoid DM1 via a non-cleavable thioether linker (SMCC). T-DM1 is administered intravenously at a dose of 3.6 mg/kg every 3 weeks (Q3W).
Trastuzumab deruxtecan (T-DXd)
Drug
Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) consisting of the humanized anti-HER2 monoclonal antibody trastuzumab covalently linked to the topoisomerase I inhibitor payload DXd via a cleavable tetrapeptide-based linker (GGFG). T-DXd is administered intravenously at a dose of 5.4 mg/kg every 3 weeks (Q3W).
Datopotamab deruxtecan (Dato-DXd)
Drug
Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to the topoisomerase I inhibitor payload DXd via a cleavable tetrapeptide-based linker (GGFG). Dato-DXd is administered intravenously at a dose of 6 mg/kg every 3 weeks (Q3W).
Sacituzumab govitecan (SG)
Drug
Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to the topoisomerase I inhibitor payload SN-38 via a cleavable pH-sensitive carbonate linker (CL2A). SG is administered intravenously at a dose of 10 mg/kg on Days 1 and 8 of each 21-day cycle.
Enfortumab vedotin (EV)
Drug
Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) consisting of a humanized anti-Nectin-4 IgG1 monoclonal antibody covalently linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a cleavable protease-sensitive linker (vc, valine-citrulline). EV is administered intravenously at a dose of 1.25 mg/kg on Days 1, 8, and 15 of each 28-day cycle.
Becotatug vedotin (MRG003)
Drug
Becotatug vedotin (MRG003) is an antibody-drug conjugate (ADC) consisting of a humanized anti-EGFR IgG1 monoclonal antibody covalently linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a cleavable protease-sensitive linker (vc, valine-citrulline). MRG003 is administered intravenously every 3 weeks (Q3W).
Izalontamab brengitecan (iza-bren / BL-B01D1)
Drug
Izalontamab brengitecan (iza-bren; BL-B01D1) is a bispecific antibody-drug conjugate (ADC) targeting both EGFR and HER3, covalently linked to a topoisomerase I inhibitor payload. BL-B01D1 is administered intravenously.
Mirvetuximab soravtansine (MIRV)
Drug
Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate (ADC) consisting of the humanized anti-FRα monoclonal antibody M9346A covalently linked to the cytotoxic maytansinoid DM4 via a cleavable disulfide linker. MIRV is administered intravenously at a dose of 6 mg/kg adjusted ideal body weight (AIBW) on Day 1 of every 3-week cycle (Q3W).

Treatment groups

225 Participants

are divided into 5 treatment groups

Group A: HER2-directed molecular cohortExperimental treatment 2 interventions

Group B: TROP2-directed molecular cohortExperimental treatment 2 interventions

Group C: Nectin-4-directed molecular cohortExperimental treatment 1 intervention

Group D: EGFR-directed molecular cohortExperimental treatment 2 interventions

Group E: FRα-directed molecular cohortExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Objective Response Rate (ORR) as Assessed by RECIST 1.1

ORR is defined as the proportion of participants achieving a best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 criteria, as assessed by the investigator.

Time frame

Up to 104 Weeks

Secondary outcomes

Disease Control Rate (DCR) as Assessed by RECIST 1.1

Disease Control Rate (DCR), defined as the proportion of patients achieving a best overall response of complete response (CR), partial response (PR), or stable disease (SD), as assessed by RECIST 1.1.

Time frame

Up to 104 Weeks

Duration of Response (DoR)

DoR is defined as the time from the first documented response (CR or PR) to the first documented disease progression or death from any cause, as assessed by RECIST 1.1.

Time frame

Up to 104 Weeks

Progression-Free Survival (PFS)

Progression-Free Survival (PFS), defined as the time from the start of treatment to the first documented disease progression or death from any cause, whichever occurs first, as assessed by RECIST 1.1.

Time frame

Up to 104 Weeks

Overall Survival (OS)

Overall Survival (OS), defined as the time from the start of treatment to death from any cause.

Time frame

Up to 104 Weeks

Other outcomes

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0

A TEAE is defined as any adverse event that starts or worsens in severity after the first dose of study treatment. Severity graded per NCI CTCAE v5.0.

Time frame

Up to 104 Weeks

Absolute Quantification Value of Target Antigen by Mass Spectrometry

The absolute quantity of the target antigen will be measured in tumor tissue samples collected at baseline using a validated mass spectrometry-based assay.

Time frame

Baseline

Sponsors and contacts

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

Fudan University

Lead sponsor

Source ClinicalTrials.gov

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