A Study of Disitamab Vedotin with Other Anticancer Drugs in Solid Tumors

You may be able to join if

• Histologically or cytologically confirmed diagnosis of breast carcinoma or gastric or gastroesophageal junction adenocarcinoma
• HER2-low status determined by most recent local assessment (IHC 1+ or IHC 2+/in situ hybridization (ISH)-negative) based on American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) guidelines for assessment of HER2 in BC for interpretation of HER2 expression and amplification or must have HER2-low expression defined as IHC 1+ or IHC 2+/ISH-negative determined by most recent local assessment based off the ASCO and CAP guidelines for assessment of HER2 in gastric cancer (GC) for interpretation of HER2 expression and amplification. -or-
• HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+) according to ASCO and CAP guidelines for assessment of HER2 in BC or GC/GEJC
• Prior therapies requirements: In HER2-Low Breast Cancer participants: a. No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC. Participants previously treated with (neo)adjuvant cytotoxic chemotherapy and have disease relapsed within 6 month of treatment is considered to have received 1 line of cytotoxic therapy for LA/mBC. b. Participants with known germline BRCA mutation must have received a PARP-inhibitor, where available and not medically contraindicated c. Have progression on or after, or be intolerant to, trastuzumab deruxtecan (T-DXd) d. Participants with hormone receptor-positive (HR+) tumors must have intolerance to endocrine therapy or endocrine therapy refractory disease: i. Progressed on ≥2 lines of endocrine therapy for LA/mBC AND had received a CDK4/6 inhibitor in the adjuvant or metastatic setting if available as local standard of care and not contraindicated OR ii. 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 if available as local standard of care and not contraindicated iii. Note that prior endocrine and CDK4/6 inhibitor therapy for low ER and PR expression (immunohistochemical staining of only 1 to 10% of tumor cells) is per institutional standard and not mandated prior to enrollment iv. Participants with HR+ HER2-low tumors must have progression on or after, or be intolerant to, prior cytotoxic chemotherapy (including ADCs) if available as local standard of care for endocrine therapy refractory advanced disease. e. Participants with hormone receptor (HR) negative, HER2-low and programmed cell death receptor ligand 1 (PD-L1)-positive 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. In HER2+ Breast Cancer participants: a. Received first line standard of care therapy for advanced disease (e.g. trastuzumab, pertuzumab and a taxane or T-DXd based therapy). b. Have progression on or after, or be intolerant to, T-DXd c. No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC
• All participants in: HER2-Low Gastric or Gastroesophageal Junction Adenocarcinoma must have: a. Prior systemic therapy with platinum, fluorouracil, or taxane for locally advanced unresectable or metastatic disease b. Progression within 6 months of last dose of (neo)adjuvant cytotoxic chemotherapy is considered as 1 line of systemic therapy for LA/mGC/GEJC c. Prior anti-PD-(L)1 (programmed cell death receptor 1 [PD1] and PD-L1, collectively) therapy is allowed d. No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADC) for LA/mGC/GEJC HER2+ LA/m Gastric or Gastroesophageal Junction Adenocarcinoma must have: a. Received prior trastuzumab plus fluoropyrimidine and platinum containing chemotherapy if no contraindication. b. Prior T-DXd treatment is allowed c. Prior PD1 inhibitor therapy is allowed d. No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mGC/GEJC.
• Note that gastric cancer cohorts are closed for enrollment. There are no LA/mGC/GEJC participants in the dose optimization and expansion phases.