Patients must have had =< 1 prior cytotoxic regimen for metastatic disease (unless enrolling in the Progressive Brain Metastases Cohort); note that endocrine and immunotherapies do not count as cytotoxic regimens
For dose-expansion cohort only: no more than two prior systemic chemotherapy-containing regimens in the advanced/metastatic setting (excluding trastuzumab emtansine, which is considered a targeted cytotoxic agent)
Receipt of more than 3 prior regimens of cytotoxic chemotherapy for metastatic disease unless prior approval is granted by the Sponsor.
Part A) Triple-negative disease (ER/PR/HER2-negative) and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting; or ER-positive and/or PR-positive/HER2-negative disease and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting and are no longer a candidate for hormonal therapy (not enrolling new patients);
Part B) Combination Arm: HER2-positive disease and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting (not enrolling new patients);
Up to 3 prior cytotoxic chemotherapeutics regimens or myelosuppressive therapies in the advanced setting.
No more than two prior lines of cytotoxic-containing chemotherapy regimens for advanced disease. There is no limit for prior targeted therapy, hormonal therapy and immunotherapy (such as nivolumab).
More than two prior cytotoxic chemotherapy regimens for the treatment of mCRPC
Patients must have NOT received more than two total prior lines of cytotoxic chemotherapy for management of recurrent or persistent disease, including re-treatment with initial chemotherapy regimens
No more than 3 prior regimens of cytotoxic chemotherapy unless approved by the sponsor (Note: all platinum-containing regimens are not to be counted separately but are considered to be a single regimen for the purposes of this criterion)
Patient must have received =< 3 prior cytotoxic regimens in the metastatic setting
For both the extension and expansion cohorts, patients must have received or refused first line standard systemic therapy for their metastases (if applicable) and patients (pancreatic and esophageal cancers) must have received no more than two prior cytotoxic chemotherapy regimens in the last two years after standard therapy; patients (breast, ovarian and gastrointestinal cancers) must have received no more than three prior cytotoxic chemotherapy regimens in the last two years after standard therapy
Patients who have received more than 2 systemic cytotoxic chemotherapy regimens for metastatic urothelial carcinoma\r\n* Note: prior perioperative chemotherapy is allowed and is not counted as a line of therapy
Participants must have received prior platinum-based chemotherapy for management of\n             primary disease but must not have received more than 2 prior systemic cytotoxic\n             regimens.
No more than 5 total previous regimens of systemic therapy, including cytokines and cytotoxic chemotherapy.
More than 3 prior systemic anti-cancer therapies (e.g. cytotoxic agents, biologic agents) regimens for metastatic disease
Patients are allowed to have received up to three prior cytotoxic regimens for treatment of their epithelial ovarian, fallopian tube, or primary peritoneal cancer; they must have had one prior platinum-based chemotherapeutic regimen for management of primary disease, possibly including intra-peritoneal therapy, consolidation, biologic/targeted (non-cytotoxic) agents or extended therapy (maintenance/consolidation) administered after surgical or non-surgical assessment; patients are allowed to have received, but are not required to have received, one to two cytotoxic regimens for management of recurrent or persistent disease; (for the purposes of this study poly adenosine diphosphate [ADP] ribose polymerase [PARP] inhibitors given for recurrent or progressive disease will be considered cytotoxic; PARP inhibitors given as maintenance therapy in continuation with management of primary disease will not be considered as a separate cytotoxic regimen); if two cytotoxic regimens had been received for management of recurrent or persistent disease, one of these regimens would have had to contain either a platinum or a taxane agent
Patients who have received more than 2 prior non-docetaxel containing cytotoxic chemotherapy regimens for Metastatic Castration-Resistant Prostate Cancer (mCRPC).
Up to 2 prior cytotoxic regimens for advanced or metastatic breast cancer patients with no prior cytotoxic regimens for advanced or metastatic disease will only be allowed if they relapsed during or within 12 months of (neo-) adjuvant cytotoxic therapy that included a taxane and/or anthracycline, if not contraindicated.
Participants must have received no more than 3 prior chemotherapy or cytotoxic regimens; there is no limit to the number of prior hormonal therapies
Inclusion Criteria.\n\n          -  Have a diagnosis of Hormone Receptor Positive (HR+), Human Epidermal Growth Factor\n             Receptor 2 Negative (HER2-) breast cancer.\n\n          -  Recurrent, locally advanced, unresectable or metastatic breast cancer with disease\n             progression following anti-estrogen therapy.\n\n          -  Prior treatment with at least 2 chemotherapy regimens:\n\n               -  At least 1 of these regimens must have been administered in the metastatic\n                  setting.\n\n               -  At least 1 of these regimens must have contained a taxane.\n\n               -  No more than 2 prior chemotherapy regimens in the metastatic setting.\n\n          -  Have a performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group\n             scale.\n\n          -  Have discontinued all previous therapies for cancer.\n\n          -  Have the presence of measureable disease as defined by Response Evaluation Criteria in\n             Solid Tumors Version 1.1.\n\n        Exclusion Criteria:\n\n          -  Have either a history of central nervous system (CNS) metastasis or evidence of CNS\n             metastasis on the magnetic resonance image of brain obtained at baseline.\n\n          -  Received prior therapy with another cyclin-dependent kinases 4 and 6 (CDK4/6)\n             inhibitor.\n\n          -  Have received treatment with a drug that has not received regulatory approval for any\n             indication within 14 or 21 days of the initial dose of study drug.\n\n          -  Have had major surgery within 14 days of the initial dose of study drug.\n\n          -  Have a history of any other cancer (except non-melanoma skin cancer or carcinoma\n             in-situ of the cervix).
Participants may have had up to two previous cytotoxic therapeutic regimens provided these were discontinued >= 4 weeks before starting the trial
Experienced progression after one or more prior regimens of cytotoxic chemotherapy
Patients who have had 2 or more regimens containing cytotoxic chemotherapy for metastatic melanoma.
Patient must have received =< 3 prior cytotoxic regimens for metastatic breast cancer; this does not include cytotoxic regimens used in the adjuvant setting
More than 4 prior cytotoxic chemotherapy regimens
Patients may not have received more than 2 prior cytotoxic regimens
Patients are allowed to have previously received, but are not required to receive, one or two additional cytotoxic regimens for management of recurrent or metastatic disease according to the following definition: cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
More than 2 prior cytotoxic chemotherapy regimens for relapsed or metastatic disease
Received at least two prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease.
At least one of the prior systemic cytotoxic chemotherapy regimens for unresectable, locally advanced or metastatic disease must have contained gemcitabine and have met the following criteria:
Subject has received more than 5 prior cytotoxic agent-containing regimens.
May be systemic naïve or received up to two previous systemic treatment regimens for metastatic melanoma.
Prior treatment with more than two regimens of systemic cytotoxic chemotherapy for locally recurrent or metastatic disease
More than two regimens of systemic cytotoxic chemotherapy for recurrent or advanced NSCLC
Receipt of 2 or more prior cytotoxic chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer.
Patients may have received, but are not required to have received, one or two additional cytotoxic regimens for management of recurrent or persistent disease
More than two regimens of cytotoxic chemotherapy for the treatment of locally advanced or metastatic cancer
Prior treatment with greater than (>) one cytotoxic chemotherapy regimens or experienced recurrent or progressive disease on > two endocrine therapies for MBC
More than 2 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease
Patients may not have received more than 2 prior cytotoxic regimens