SGNDV-004 is a phase 1b/2 open-label, multicenter study that will enroll subjects with locally advanced or metastatic gastric cancer, gastroesophageal cancer, and locally advanced or metastatic breast cancer (LA/mGC/GEJC and LA/mBC) that express HER2.
The study has a dose escalation phase evaluating disitamab vedotin plus tucatinib followed by a dose optimization phase. The 2 dose levels identified in the dose escalation phase will be assessed in the optimization phase for both safety and efficacy in HER2-low LA/mBC subjects. Once the safety and efficacy profile of disitamab vedotin plus tucatinib has been established and a disitamab vedotin dose with the optimum benefit/risk ratio has been determined the disitamab vedotin plus tucatinib combination therapy will be evaluated in an expansion phase with 2 expansion cohorts in subjects with HER2-low mGC/GEJC and HER2 + LA/mBC.
Get started
Answer a 2-minute questionnaire and speak to a study representative.
A first step as you consider connecting with a Principal Investigator is to answer a 2-minute online questionnaire about your interest and willingness to be contacted. If your answers show the study might be a good fit for you and your patient, you may choose to have your contact information shared with a study clinic that you select for further discussion.
Get connected.
Your answers to these questions will only be linked to you if your responses indicate that you would like to be connected with a Principal Investigator and you choose to share your contact information with the study clinic. Pfizer study team members and our partners will have access to reports containing aggregated data that will not be directly linked back to you. Only the study staff can determine if your patient meets the study’s eligibility criteria and is able to enroll in the study.
Arms and Interventions
Dose Escalation Phase
Population and HER2 Status
HER2-expressing (IHC 1+ or higher) 2L LA/mGC/GEJC, or 3L or higher LA/mBC
Open-Label Study Treatment
Combination therapy: Disitamab vedotin (dose may vary) + Tucatinib (fixed dose)
Optimization/Expansion
(Planned/Not enrolling yet)
Population and HER2 Status
TBD
Open-Label Study Treatment
TBD
Inclusion Criteria
This is not a complete list of inclusion and exclusion criteria. Please connect with a Principal Investigator for further information.
General Inclusion criteria
- Measurable disease according to RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
Dose escalation cohort
- Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma
- Locally-advanced, unresectable, or metastatic stage
- HER2 status IHC 1+ or higher by most recent local assessment.
- Must have experienced disease progression on or after standard of care therapies or be intolerant of standard of care therapies.
Exclusion Criteria
This is not a complete list of inclusion and exclusion criteria. Please connect with a Principal Investigator for further information.
- 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
Primary outcomes
- 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
Secondary outcomes
- Duration of response (DOR) per RECIST v1.1 by investigator assessment
- Disease control rate (DCR) per RECIST v1.1 by investigator assessment
- Progression free survival (PFS) per RECIST v1.1 by investigator assessment
- Overall survival (OS)
- Pharmacokinetic (PK) parameter - Maximum concentration (Cmax)
- PK parameter - Area under the concentration-time curve to the time of the last quantifiable concentration (AUClast)
- Incidence of anti-drug antibodies (ADAs) against disitamab vedotin
Protocol Amendment 01, DV-004 HCP Page, 14Aug24