Active scleroderma or calcinosis cutis with features of Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome Patients with esophageal cancer with unresected or recurrent primary tumors in the esophagus are only permitted after discussion of patient with study chair Any dysphagia, odynophagia, esophageal dysmotility or stricture, known GI malabsorption syndrome, or intractable diarrhea that may significantly alter the absorption of any of the components of SM-, e.g., cirrhosis. Any solid malignancy known to be MSI high/MMR deficient per local test results, including but not limited to: CRC, stomach adenocarcinoma, esophageal adenocarcinoma and endometrial cancer Phase a: ISH positive or IHC + advanced cancer (including breast or gastric/esophageal or other solid tumors). Histologically proven (squamous cell or adenocarcinoma) esophageal or gastro- esophageal junction cancer (core biopsy required) Diagnosed with cervical esophageal carcinoma History of esophageal cancer more extensive than Ta or not meeting criteria for low risk of recurrence (confirmed by EMR pathology results negative for positive margin, poorly differentiated carcinoma, and lymphovascular invasion) Any clinical or histological suspicion of esophageal adenocarcinoma invading into the submucosa by endoscopic mucosal resection (EMR), or confirmed Ta cancer with positive deep margin by EMR All conditions associated with significant necrosis of nontumor-bearing tissues: esophageal or gastroduodenal ulcers < months prior to enrollment, organ infarction < months prior to enrollment, or active ischemic bowel disease Diagnosis of cervical esophageal carcinoma Any prior anticancer therapy for esophageal cancer Has biopsy-proven invasion of tracheobronchial tree or tracheo-esophageal fistula Prior endoscopic mucosal resection (EMR) with a diagnosis of stage II or III esophageal cancer is eligible, irrespective of margin status The patient has undergone any facial, esophageal, gastric or sinus surgery within the last months. Patients (both male and female) with advanced/metastatic GI cancers eligible for capecitabine monotherapy, including metastatic colorectal cancer, metastatic gastric and esophageal cancers, and unresectable or metastatic pancreatic cancer and cholangiocarcinoma, including gall bladder carcinoma, concurrent trastuzumab is allowed for HER positive gastric/esophageal cancer Untreated or poorly controlled gastro-esophageal reflux disease Previous esophageal dilatation is permitted, provided the patient has developed recurrent dysphagia since that procedure Prior history of esophageal perforation Histologically or cytologically confirmed diagnosis of advanced stage gastric, gastro-esophageal, or esophageal cancers in whom ramucirumab and paclitaxel are reasonable treatments Cervical esophageal cancer will not be entered in this study Occurrence of esophageal or other gastrointestinal hemorrhage requiring transfusion within weeks prior to the Baseline Visit. Patient that is contraindicated to upper GI endoscopy and/or any procedure to be performed in conjunction with esophageal stent placement Potentially resectable or unresectable esophageal cancer patients Prior endoscopic mucosal resection (EMR) with a diagnosis of stage II-III esophageal cancer is eligible Any patient deemed eligible for chemoradiation for esophageal cancer treatment Patients with active second malignancy are allowed as long as it is determined by the treating physician that the treatment of esophageal cancer is of higher priority through proper evaluation; however patients with active stage , metastatic cancers, receiving other systemic therapies at the time of the esophageal cancer diagnosis, will not be eligible Patients must not have had prior chemotherapy or radiation therapy for esophageal cancer Patients with cervical esophageal carcinoma Patients with TN disease, T disease, and proximal esophageal cancers (- cm) Has had esophageal or gastric variceal bleeding within the last months. gastric cancer (including gastro-esophageal junction) Has had esophageal or gastric variceal bleeding within the last months History of Barrett's esophagus, esophageal webbing, stricture, or fistula Histologically confirmed, unresectable, metastatic diffuse gastric cancer including carcinoma of the gastro-esophageal junction Has locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy (as determined by local investigator) Patients with active second malignancy are allowed as long as it is determined that the treatment of esophageal cancer is a higher priority through proper subspecialty consultations Patients must have histologically confirmed gastric, gastro-esophageal junction or distal esophageal adenocarcinoma (predominant histology) that is recurrent, metastatic or unresectable Gastric or Gastro-Esophageal junction carcinoma (No longer enrolling this tumor type) Esophageal variceal bleeding within weeks prior to the first dose of TKM-. Patient has previously undergone esophageal stenting or esophagectomy Patient has trouble swallowing or experiences regurgitation for reasons which are not related to his/her esophageal cancer Esophageal or gastric variceal bleeding within last months Has biopsy-proven invasion of tracheobronchial tree or tracheo-esophageal fistula Mean esophageal radiation dose > Gy Subjects with an esophageal stent in situ at the time of study enrollment Subject has had previous Spray Cryotherapy for esophageal cancer. Esophageal carcinoma, undergoing minimally invasive esophagectomy with intrathoracic anastomosis Diagnosed with incurable (defined as metastatic or receiving chemotherapy with palliative intent) esophageal, gastric, pancreas, hepatobiliary, colorectal, or lung cancer within the prior weeks (including patients with prior diagnosis of cancer who developed incurable disease) Undergoing primary resection of esophageal cancer and resultant esophagectomy Diagnosed with pancreatic, esophageal, rectal, colon, hepatobiliary, or gastric cancer (including patients with prior diagnosis of another cancer) Recent esophageal, gastric or bowel surgery (within weeks of study enrollment) Inability to increase food intake (e.g., esophageal obstruction, intractable nausea and vomiting) Subjects with malignant dysphagia due to esophageal cancer or esophagogastric junction cancer who are undergoing upper endoscopic ultrasound or upper endoscopy for pre-treatment staging or symptom evaluation Tracheo-esophageal fistula Presence of an esophageal or duodenal stent Patients with known, untreated esophageal strictures, prior partial esophageal resection, or altered anatomy preventing passage of the endomicroscope Patients who had esophageal therapy with Halo radiofrequency ablation in the past, or esophagectomy Esophageal ulcerations Esophageal candida Subjects with known esophageal cancer diagnosed by previous endoscopy\r\n* Adenocarcinoma\r\n* Squamous cell carcinoma Patients determined to be at risk for esophageal cancer:\r\n* Subjects with a history of Barretts esophagus\r\n* Subjects with a history of low or high grade dysplasia\r\n* Subjects with a history of gastroesophageal reflux disease (GERD)\r\n* Subjects with a history of esophagitis\r\n* Subjects with symptoms of esophageal cancer (EC) referred for endoscopy (new onset dysphagia, weight loss, etc) Patients with esophageal dysmotility Prior history of esophageal cancer Subjects may have a history of prior malignancy except for esophageal adenocarcinoma Esophageal adenocarcinoma Gastric and esophageal cancer History of esophageal or gastric surgery Presence of an esophageal stricture defined as any recognizable change in esophageal luminal caliber that is accompanied by symptoms of dysphagia, or any asymptomatic narrowing that either will not allow any adult endoscope to pass or allows passage with resistance Patients undergoing esophageal resection Patients with esophageal cancer receiving trastuzamab Subjects with known esophageal cancer (adenocarcinoma or squamous cell carcinoma) Subjects with risk factors for esophageal malignancy including Barretts esophagus and gastroesophageal reflux disease (GERD) Subjects with completely obstructing esophageal cancer Subjects with cervical or Siewert esophageal carcinoma, that are recommended by the multi-disciplinary tumor board to have treatment other than tri-modality chemo-radiation therapy (RT) followed by esophagectomy Dose and Disease Expansion Cohorts: histologically confirmed renal cell carcinoma, gastric carcinoma (including gastro-esophageal junction adenocarcinoma), and a biomarker driven cohort of tumors with evidence of c-MET dysregulation (amplification, mutation) Prior esophageal or gastric surgical resection. Patients with Barretts esophagus scheduled for esophageal surgery Patients with gastroesophageal reflux disease (GERD), but without Barretts esophagus scheduled for esophageal surgery Previous esophageal procedure (surgery, photodynamic therapy, argon plasma coagulation, endoscopic mucosal resection) Requires a clinically necessary esophagectomy for esophageal cancer or other indications. Patient has esophageal narrowing limiting access to the intended sites of ablation Previous history of a swallowing disorder, such as scleroderma, achalasia, esophageal stricture or esophageal diverticulum