C5731004 - SGNDV-004 - A Phase 1b/2 Open-Label Study of Disitamab Vedotin in Combination With Other Anticancer Therapies in Solid Tumors

Studio Clinico

Patologia: Neoplasie della mammella, Neoplasie dello stomaco, Tumori dell’esofago

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: 1, I B, II

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

General Inclusion Criteria
- Measurable disease according to RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

Dose Escalation and Optimization Phase Inclusion Criteria
- Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma
- Locally-advanced, unresectable, or metastatic stage
- Must have experienced disease progression on or after standard of care therapies or be intolerant of standard of care therapies.

Cohort A (HER2-Low Breast Cancer) Inclusion Criteria
- Locally-advanced, unresectable, or metastatic stage
- HER2-low status determined by most recent local assessment (IHC 1+ or IHC 2+/ISH-negative)

Prior therapies requirements
- No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC.
- Participants with known BRCA mutation must have received a PARP-inhibitor where available and not medically contraindicated
- Have progression on or after, or intolerant to, T-DXd, sacituzumab govitecan, or other topoisomerase I inhibitor therapies, if available as local standard of care therapy
- Participants with HR+ tumors must have intolerance to endocrine therapy or endocrine therapy refractory disease
- Participants with HR negative, HER2-low and PD-L1-positive (CPS 10 or greater) tumors must have received pembrolizumab with chemotherapy if available as local standard of care therapy.
- Participants with HR negative, HER2-low and PD-L1-positive (CPS 10 or greater) tumors must have received pembrolizumab (or other PD-(L)1 inhibitor) with chemotherapy if available as local standard of care therapy and not medically contraindicated

Cohort B (HER2+ Breast Cancer) Inclusion Criteria
- Locally-advanced, unresectable, or metastatic stage
- HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+)
- Participants must have:
    ▪ Received prior trastuzumab, pertuzumab and a taxane if available as local standard of care therapy for advanced disease.
    ▪ Have progression on or after, or intolerant to, T-DXd or other topoisomerase I inhibitor therapies
    ▪ No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC

Cohort C (HER2-Low Gastric or Gastroesophageal Junction Adenocarcinoma) Inclusion Criteria
- Locally-advanced, unresectable, or metastatic stage
- HER2-low expression defined as IHC 1+ or IHC 2+/ISH-negative determined by most recent local assessment
- Willing and able to provide archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks
- Participants must have received:
    ▪ Prior systemic therapy with platinum, fluorouracil, or taxane for locally advanced unresectable or metastatic disease
    ▪ Progression within 6 months of last dose of (neo)adjuvant cytotoxic chemotherapy is considered as 1 line of systemic therapy for LA/mGC/GEJC
    ▪ Prior anti-PD-(L)1 therapy is allowed
    ▪ No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADC) for LA/mGC/GEJC
- Must not have received prior treatment with HER2 directed therapy

Cohort D (HER2+ LA/mGC/GEJC) Inclusion Criteria
- Locally-advanced, unresectable, or metastatic stage
- HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+)
- Participants must have:
    ▪ Received prior trastuzumab plus fluoropyrimidine and platinum containing chemotherapy if no contraindication.
    ▪ Prior T-DXd treatment is allowed
    ▪ Prior PD1 inhibitor therapy is allowed
    ▪ No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mGC/GEJC.

Criteri di esclusione: 

- Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin or tucatinib
- Prior therapy with ADCs with MMAE payload
- Prior therapy with tucatinib
- Active CNS and/or leptomeningeal metastasis.
- Participants who have received prior systemic anticancer treatment including investigational agents within 4 weeks prior to first dose of study treatment
- History of other invasive malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
- Unable to swallow oral tablets or capsules or any significant GI disease which would preclude the adequate oral absorption of medications.

Numero di pazienti previsti: 

18

Schema di trattamento: 

Experimental: Dose Escalation - Previously treated advanced GC/GEJC or breast cancer
disitamab vedotin + tucatinib
Experimental: Dose Optimization - HER2-low and HER2+ LA/mBC
disitamab vedotin + tucatinib
Experimental: Dose Optimization - HER2-low and HER2+ LA/mGC/GEJC
disitamab vedotin + tucatinib
Experimental: Dose Expansion - HER2-low LA/mBC
disitamab vedotin + tucatinib
Experimental: Dose Expansion - HER2+ LA/mBC
disitamab vedotin + tucatinib
Experimental: Dose Expansion - HER2-low LA/mGC/GEJC
disitamab vedotin + tucatinib
Experimental: Dose Expansion - HER2+ LA/mGC/GEJC
disitamab vedotin + tucatinib

Trattamento sperimentale: 

disitamab vedotin + tucatinib

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

- Number of participants with dose limiting toxicities (DLTs) in dose escalation phase
- Number of participants with adverse events (AEs)
- Number of participants with laboratory abnormalities
- Number of participants with dose alterations
- Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment.

Centri partecipanti

Nord Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2023-507555-29-00

Data di inserimento: 17.04.2025

Promotore

Seagen Inc.

Principal Investigator ITALIA

Riferimento: Dr. Info non applicabile

Telefono: 00000

Email: na@na.it

Localita: na