Pathologically confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma (GBC), having received at least prior line of systemic therapy, and received no more than prior lines of therapy in the metastatic setting (disease recurrence < months from the last dose of adjuvant therapy in resected patients will be considered the first line of therapy)\r\n* Includes intrahepatic cholangiocarcinoma (IHC), extrahepatic cholangiocarcinoma (EHC), and gallbladder carcinoma (GBC), but not ampulla of vater cancers Patients receiving targeted therapy (non-cytotoxic, non-immunotherapy based systemic therapy) for NSCLC in the first-line setting. Such designations would include but not be limited to treatments targeting EGFR mutant positive or ALK positive NSCLC in the first-line setting. Biopsy-proven metastatic pancreatic adenocarcinoma with documented radiographic disease progression on or after one or more systemic therapies. Chemotherapy given as part of prior chemoradiation in the setting of non-metastatic pancreatic cancer does not count as a line of therapy. Chemotherapy given for at least months as adjuvant after complete response is considered as a first line therapy. One prior systemic therapy in the metastatic setting is allowed, but patients who have not had any prior systemic therapies in the metastatic setting are also eligible\r\n* Note: patients who were started on endocrine therapy monotherapy as their st line or nd line systemic therapy in the metastatic setting for no more than days and without clinical progression prior to the initiation of the study drug therapy are allowed to enroll on the study as their st line or nd line therapy, respectively Patients can be treated either in first line or in the refractory setting; PD-L positivity is not required for enrollment Arm A: MBC with progression and no prior endocrine based systemic therapy in the metastatic setting; Arm C: MBC with progression during or following one or two prior endocrine based systemic therapies in the metastatic setting, and following prior therapy with a CDK inhibitor. Prior treatment with at least one, and no more than three, lines of therapy overall in the metastatic setting. Patients must have progressed on or following, the most recent line of therapy. Patients must have had at least one line of therapy in the metastatic setting Patients must have had at least one prior line of therapy for breast cancer in the metastatic setting Both patients with stage IV and patients with recurrent disease after progression must have had at least line of standard systemic therapy in the advanced/metastatic setting; a. patients with HER-positive disease must have had at least lines of anti-HER therapy, including Perjeta and Kadcyla in the metastatic setting; b. prior eribulin treatment is allowed Prior therapy exclusions:\r\n* Prior therapy with fulvestrant\r\n* Prior therapy with tamoxifen in the metastatic setting\r\n* More than prior lines of endocrine therapy in the metastatic setting\r\n* More than one prior line of chemotherapy in the metastatic setting Patients must be in consideration for st line systemic therapy for recurrent IBC; NOTE: Patients must not have received chemotherapy in the metastatic setting, but adjuvant treatment after surgery is acceptable Metastatic colorectal cancer patients \r\n* Patient must have received a minimum of systemic therapy in the metastatic setting Phase I only: Histologic confirmation of pancreatic, colorectal, gastroesophageal or biliary adenocarcinoma, as follows:\r\n* Patients with metastatic disease from pancreatic cancer who received no more than lines of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from colorectal cancer who received no more than lines of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from gastroesophageal cancer who received no more than line of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from biliary tract cancer who received no more than line of prior therapy in the metastatic setting\r\n* NOTE: No prior exposure to irinotecan in the metastatic setting will be allowed except in the phase I dose escalation portion and in colon cancer patients only; in pancreas cancer, exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < months from last dose of irinotecan Phase Ib only: Histologic confirmation of pancreatic or gastroesophageal adenocarcinoma, as follows:\r\n* Patients with metastatic disease from pancreatic cancer who received no more than line of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from gastroesophageal cancer who received no more than line of prior therapy in the metastatic setting\r\n* NOTE: No prior exposure to any irinotecan in the metastatic setting will be allowed Patients must have received at least one prior line of chemotherapy, for ULMS (either in the adjuvant or metastatic setting) POSTMENOPAUSAL ELIGIBILITY: \r\n* Postmenopausal women who have progressed on first-line or second line therapy with an aromatase inhibitor in the metastatic setting\r\n* Postmenopausal women who have recurred while on or after completion of adjuvant treatment with aromatase inhibitors (they have completed at least one year of AI in the adjuvant setting before progression on AI)\r\n* Postmenopausal women who are not considered candidates for treatment with an aromatase inhibitory by their oncologist, patients not willing to go on AI, or patients who were intolerant to AI\r\n* Postmenopausal women are allowed (but not required) to have up to two lines of prior chemotherapy regimens in the metastatic setting for the dose expansion phase; for the dose escalation cohort, up to three previous lines of chemotherapy in the metastatic setting is acceptable All patients should have received at least one line of chemotherapy in either the advanced or adjuvant setting and hormonal therapy (where appropriate) Have received no more than one prior systemic chemotherapy regimen in the relapsed or metastatic setting. Prior treatment with no more than one prior immune checkpoint inhibitor is permitted and will not be considered as a line of systemic chemotherapy. Disease progression during or within months after treatment with one line of -Fluorouracil (-FU)- or gemcitabine-based chemotherapy in the metastatic setting Subjects must have received at least one line of hormonal therapy in the metastatic setting Patients enrolling onto Arm C (FOLFIRI) or Arm D (MM- with -FU and leucovorin) must have failed one prior line of gemcitabine-based therapy with or without BBI in the metastatic setting. No additional lines of therapy in the metastatic setting are allowed. Prior adjuvant therapy with gemcitabine is allowed as long as disease recurrence occurred > months of last dose of therapy. Toxicities related to prior therapy must have completely resolved (except for alopecia and anemia), or be deemed irreversible. Prior treatment with radiotherapy is allowed. Prior treatment with standard first line therapy in the metastatic setting Subject has received > prior line of chemotherapy in the metastatic setting Prior therapies:\r\n* All women: at least one prior line of hormonal therapy for de novo disease (stage IV metastatic at diagnosis, no prior adjuvant therapy) or relapse > year after completion of adjuvant therapy; relapse on adjuvant hormonal therapy will count as the one prior line of therapy\r\n* All women: at least prior line of chemotherapy in the adjuvant and/or metastatic setting, but not more than regimens in the metastatic setting Patients with ER and/or PR- positive/ HER non-amplified invasive mammary carcinoma must have had at least one line of endocrine therapy in the metastatic setting, or be diagnosed with metastatic breast cancer during or within year of adjuvant endocrine therapy; there is no limit on lines of prior treatment in the metastatic setting Patients with ER and/or PR-positive/ HER-amplified invasive mammary carcinoma must have had at least one line of HER-targeted therapy in the metastatic setting, or be diagnosed with metastatic breast cancer during or within year of adjuvant HER-targeted therapy; there is no limit on lines of prior HER-targeted treatments in the metastatic setting Prior endocrine therapy in the metastatic setting may include any aromatase inhibitor (AI) or tamoxifen, but may not include prior fulvestrant; in the metastatic setting, - prior lines of endocrine therapy are allowed Prior treatments:\r\n* Subjects should have received at least two approved HER-targeted agents (trastuzumab, pertuzumab, or TDM-) in the course of their disease\r\n* Subjects should have had at least line of prior HER-targeted therapy in the metastatic setting, with the exception of asymptomatic subjects with oligometastatic or bone/soft tissue only disease who, on investigator opinion, are appropriate for a single agent antiendocrine therapy per National Comprehensive Cancer Network (NCCN) guidelines\r\n*Subjects who have had up to lines of prior endocrine therapy in the metastatic setting are allowed; prior adjuvant and/or neoadjuvant endocrine regimens are allowed and not counted towards this limit Participants who have received > prior line of chemotherapy in the advanced or metastatic setting. (Immunotherapy will not be considered a line of chemotherapy.) Patients must have received at least two lines of systemic therapy for breast cancer in the metastatic setting; patients who are hormone receptor positive must have received at least one line of hormonal therapy AND one line of chemotherapy in the metastatic setting Documented radiographic disease progression following at least one line of therapy in the advanced/metastatic setting Patients may have had up to prior line of therapy (cytotoxic therapy only) in the recurrent setting; bevacizumab in the upfront setting is allowed, however bevacizumab or other vascular endothelial growth factor (VEGF) pathway targeted therapy in the recurrent setting is not allowed; hormonal therapy does not count as a prior line Patients may not have received more than prior line of endocrine therapy in the metastatic setting At least one line of endocrine therapy in the metastatic setting Part , Dose exploration, CRC subjects can be treatment nave but should not have received more than one line of systemic therapy in the recurrent/metastatic setting. At least one prior line of chemotherapy in the metastatic setting Subjects must have received at least one line of hormonal therapy in the metastatic setting. Subjects who are eligible as per the Investigator's assessment and according to the local label for treatment with exemestane and everolimus as a second line or greater of hormone therapy in a metastatic setting. Phase Ib dose escalation only: Any number of prior lines of endocrine therapy is allowed with the exception of cytotoxic therapy which is limited to one prior line administered in the advanced (metastatic or locally advanced) setting.