Assessment of HER status in patients with gastric and gastroesophageal junction adenocarcinoma should follow the criteria published by Ruschoff et al. () as practicable.
Patients with breast cancer and gastric and gastroesophageal junction cancer must have received at least  prior HER targeted therapy for advanced/metastatic disease.
Patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, gastroesophageal junction [GEJ], cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy; patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine (dose escalation phase)
Gastric/gastroesophageal junction/esophageal carcinoma (G/GEJ/E)
Documented primary diagnosis of histologic- or cytologic-confirmed adenocarcinoma of the stomach or gastroesophageal junction.
Malignancies other than adenocarcinoma of the stomach or gastroesophageal junction (including hematologic malignancies) within  years.
Gastric or gastroesophageal junction adenocarcinoma
Histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma that is metastatic or locally advanced and unresectable
Esophageal tumors that are located in the mid esophagus or higher i.e. not involving distal esophagus or gastroesophageal (GE) junction
Diagnosed with Stage II/III carcinoma of the esophagus or gastroesophageal junction
PART II: Patients with breast cancer, gastric, gastroesophageal junction or other caners with + to + HER/neu expression by IHC or a Vysis FISH result > .
Histologically or cytologically documented adenocarcinoma or squamous cell carcinoma of the cervical or thoracic esophagus or gastroesophageal junction or cardia of stomach
Have histologically or cytologically confirmed metastatic or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma
Histologically and cytologically documented diagnosis as gastroesophageal adenocarcinoma.
Cytologic or histologic proof of adenocarcinoma of the stomach or gastroesophageal junction.
Histologically or cytologically confirmed adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach, including patients with HER+ disease; distal esophagus is defined as within  centimeters of the gastroesophageal junction (GEJ)
Histologically proven squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the esophagus or gastroesophageal (GE) junction
Patients must have histologically or cytologically confirmed gastric adenocarcinoma or gastroesophageal junction (Siewert I-III) adenocarcinoma confirmed by the Laboratory of Pathology, National Cancer Institute (NCI)
Has a pathologic diagnosis of invasive esophageal, gastroesophageal or gastric adenocarcinoma
Have previously untreated localized gastric or gastroesophageal (GE) junction adenocarcinoma as defined by T or greater primary lesion or the presence of any positive nodes-N+(clinical nodes) without evidence of metastatic disease
Diagnosis of metastatic squamous cell carcinoma and/or adenocarcinoma of the esophagus, gastroesophageal junction, or stomach in need of palliative radiotherapy to the primary tumor or a single metastatic site for symptoms such as pain, dysphagia, and/or gastrointestinal bleeding\r\n* Patients with adenocarcinoma histology and known human epidermal growth factor receptor  (HER) overexpressing disease are permitted to participate if the progressed or are intolerant of prior trastuzumab-containing therapy
Histologically or cytologically confirmed adenocarcinoma involving the gastroesophageal junction or gastric cardia
Histologically or cytologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction (EAC)
Tumor may not extend greater than  cm below the gastroesophageal junction
Histologically confirmed metastatic gastric or esophagogastric junction (type I, II, III Siewert) adenocarcinoma
Histologically documented adenocarcinoma or squamous cell carcinoma of the cervical or thoracic esophagus or gastroesophageal junction or cardia of stomach
Key inclusion criteria:\n\n          . Histologically or cytologically confirmed gastric adenocarcinoma, including gastric or\n             gastroesophageal-junction adenocarcinoma (Histologically confirmed adenocarcinoma of\n             the lower esophagus acceptable with radiographic or endoscopic documentation of\n             gastroesophageal-junction or proximal-stomach involvement.)\n\n          . Measurable disease (revised RECIST) based on computed tomography, or nonmeasurable\n             disease\n\n          . ECOG performance status  or \n\n          . Treatment with only  prior regimen (as first-line therapy) that must have included a\n             fluoropyrimidine and a platinum-containing agent (Prior adjuvant or neo-adjuvant\n             chemotherapy acceptable provided  months elapsed between the end of this therapy and\n             the start of first-line therapy.)\n\n          . Disease progression after the start of the  prior regimen based on computed\n             tomography\n\n          . Adequate bone marrow, hepatic, and renal function\n\n          . Ability to swallow an oral solid-dosage form of medication\n\n        Key exclusion criteria:\n\n          . Squamous cell gastric carcinoma\n\n          . Bone-only metastatic disease\n\n          . History or presence of brain metastasis or leptomeningeal disease\n\n          . Operable gastric or gastroesophageal-junction cancer\n\n          . HER-positive disease if the patient has not previously been treated with an anti-HER\n             agent\n\n          . Uncontrolled diarrhea, nausea, or vomiting\n\n          . Known malabsorptive disorder\n\n          . Significant medical disease other than gastric cancer\n\n          . Presence of neuropathy > Grade  (NCI Common Toxicity Criteria)\n\n         . Prior treatment (including adjuvant therapy) with a taxane or other tubulin-targeted\n             agent (indibulin, eribulin, etc.)\n\n         . Prior radiation therapy to more than % of the bone marrow\n\n         . Need to continue any regularly-taken medication that is a potent inhibitor or inducer\n             of the CYPA pathway\n\n         . Pregnancy or lactation
Expansion cohort (gastric or GE junction): histologically or cytologically confirmed diagnosis of advanced gastric cancer or GE junction with positive PD-L (threshold of positivity combined positive score [CPS] >= ) whose disease progressed on or after two or more prior systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER/neu targeted therapy, refused chemotherapy, or were not candidates for chemotherapy
Histologically-confirmed advanced or metastatic unresectable gastric carcinoma, or adenocarcinoma of the gastroesophageal junction
Unresectable locally advanced or metastatic histologically proven HER+ gastroesophageal junction (GEJ) or gastric adenocarcinoma.
Patients must have histologically or cytologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal (GE) junction\r\n* For the phase I study, patients can have disease that is deemed resectable or unresectable\r\n* For the phase II study, patients must have disease that is resectable
Must have histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma.
Histological or cytological confirmation of metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma
Has histologically confirmed non-resectable, metastatic gastric adenocarcinoma including adenocarcinoma of the gastroesophageal junction.
Histologically confirmed inoperable advanced gastric adenocarcinoma (including adenocarcinoma of the gastrooesophageal junction) or relapsed gastric adenocarcinoma
Adults with histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction that is inoperable, locally advanced or metastatic and not amenable to curative therapy
Have a histopathologically confirmed diagnosis of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. All histologies of nonsquamous cell origin including undifferentiated gastric carcinoma are eligible.
Biopsy-proven and inoperable locally advanced, recurrent, or metastatic cancer of the esophagus, stomach, or gastro-esophageal junction  adenocarcinoma type
Gastric, Esophageal, and G-E Junction Adenocarcinoma
Must have gastric cancer or gastroesophageal junction cancer that cannot be operated on and that is advanced or has spread out
Histologically or cytologically confirmed T / or N+ (>  cm in size or fludeoxyglucose F- [FDG] avid) gastric or gastroesophageal (GE) junction cancer; diagnosis must be confirmed a Dana-Farber (DF)/Harvard Cancer Center (HCC) institution pathology department prior to registration
The participant has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ).
Histologically documented adenocarcinoma or squamous cell carcinoma of the cervical esophagus, thoracic esophagus, or gastroesophageal junction
Histologically- or cytologically-confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
Cytologic or histologic proof of adenocarcinoma of the stomach or gastroesophageal junction
Patients must have metastatic disease of the esophagus, gastroesophageal junction or stomach; patients with locally recurrent disease who are not deemed eligible for radiation are also permitted\r\n* Histological, cytologic or radiographic documentation of metastatic adenocarcinoma or squamous cell carcinoma of the esophagus, gastroesophageal junction or stomach; radiologic, endoscopic, histologic or cytologic evidence of locally recurrent disease is also permitted
Histologically confirmed primary (non-recurrent) adenocarcinoma (AC) or squamous cell carcinoma of the esophagus or AC of the gastroesophageal (GE) junction
Prior surgery or radiotherapy for esophageal or gastroesophageal junction cancer
Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II, III)
Subjects must have histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the intrathoracic esophagus, gastrointestinal junction or stomach
Histological diagnosis of metastatic or locally advanced inoperable adenocarcinoma of the esophagus, gastroesophageal junction or stomach
Histologically confirmed metastatic or advanced inoperable adenocarcinoma of the stomach or gastroesophageal junction with immunohistochemistry (IHC) evidence of guanylyl cyclase C (GCC) expression indicated by an H-score of  or greater.
Treatment with  or more prior chemotherapies for advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction.
Histologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with metastatic disease documented to involve at least liver or lung or both
Advanced/unresectable or metastatic breast cancer or gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. Part a:
Advanced gastric or gastroesophageal junction adenocarcinoma with HER overexpression that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Advanced/unresectable or metastatic solid malignant tumor with HER expression other than breast cancer and gastric or gastroesophageal junction adenocarcinoma that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
Part B: Gastric or Gastroesophageal Junction (GEJ) adenocarcinoma
Assessment of HER status in subjects with gastric and gastroesophageal junction adenocarcinoma should follow the criteria published by Rschoff et al () as practicable.
All subjects with breast and gastric/gastroesophageal junction cancers should have HER testing performed using an assay kit/methodology specifically FDA-approved for their cancer type as practicable.
Participants must have a history of advanced gastric cancer (AGC), defined as\n             unresectable and locally advanced or metastatic gastric cancer, including\n             adenocarcinoma of the gastroesophageal junction (GEJ), and must have experienced\n             disease progression during or after first-line therapy for their disease
Patient has a malignant stricture of the distal esophagus or gastric cardia requiring stent placement across the gastroesophageal junction.
Subject must have histologically or cytologically confirmed gastric, or gastroesophageal adenocarcinoma, or distal esophageal adenocarcinoma.
Subject must have unresectable or metastatic gastroesophageal adenocarcinoma.
Subject with previously untreated unresectable or metastatic gastroesophageal adenocarcinoma.
Adenocarcinoma of the stomach or gastroesophageal junction with inoperable, metastatic disease, not amenable to curative therapy
Patient must have a histologic diagnosis of gastric or gastroesophageal junction adenocarcinoma
The primary tumor must originate in the esophagus; tumors that involve the gastroesophageal (GE) junction must meet Sievert type  criteria: adenocarcinoma of the distal oesophagus which usually arises from an area with specialized intestinal metaplasia of the oesophagus (i.e. Barretts oesophagus) and which may infiltrate the esophagogastric junction from above; for the purposes of this protocol, this will be interpreted as: greater than % of the tumor must be above the GE junction or, alternatively, the tumor must involve the GE junction and arise in the setting of biopsy-documented Barretts esophagus (specialized intestinal metaplasia)