A Phase 1b/2 Open-Label Study of Disitamab Vedotin in Combination With Other Anticancer Therapies in Solid Tumors
This clinical trial is studying solid tumor cancers. A solid tumor is one that starts in part of your body like your lungs or liver instead of your blood. Once they've grown bigger in one spot or spread to other parts of the body, they're harder to treat. This is called advanced or metastatic cancer. Participants in this study must have breast cancer or gastric cancer. Participants must have tumors that have HER2 on them. This allows the cancer to grow more quickly or spread faster. There are few treatment options for patients with advanced or metastatic solid tumors that express HER2. This clinical trial uses an experimental drug called disitamab vedotin (DV). Disitamab vedotin is a type of antibody drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. This clinical trial uses a drug called tucatinib, which has been approved to treat cancer in the United States and some other countries. This drug is sold under the brand name TUKYSA®. This study will test how safe and how well DV with tucatinib works for participants with solid tumors. This study will also test what side effects happen when participants take these drugs. A side effect is anything a drug does to the body besides treating the disease.
• 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
• Histologically or cytologically confirmed diagnosis of breast carcinoma
• 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:
• Progressed on ≥2 lines of endocrine therapy for LA/mBC AND had received a CDK4/6 inhibitor in the adjuvant or metastatic setting OR
∙ Progressed on 1 line of endocrine therapy for LA/mBC AND had a relapse while on adjuvant endocrine therapy after definitive surgery for primary tumor AND had received a CDK4/6 inhibitor in the adjuvant or advanced setting
⁃ 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
• Histologically or cytologically confirmed diagnosis breast carcinoma
• 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
• Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
• 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
• Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
• 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