Progression of disease after 1 or 2 prior regimens in the metastatic setting
More than one prior chemotherapy regimen administered in the metastatic setting.
Patients must meet at least one of the following criteria:\r\n* Disease progression any time after non-steroidal aromatase inhibitor (AI) use in the advanced disease setting\r\n* Relapse while on or within =< 12 months of end of adjuvant non-steroidal AI therapy with or without prior endocrine therapy for advanced disease\r\n* NOTE: In either setting, treatment with any prior endocrine therapy must be completed >= 2 weeks prior to course 1 day 1 (C1D1) of study treatment with the exception of exemestane which is permitted in the advanced disease setting within =< 4 weeks immediately prior to C1D1; prior adjuvant exemestane is allowed if the disease free interval is > 12 months from the discontinuation of exemestane; prior faslodex, everolimus, palbociclib or other cyclin-dependent kinase (CDK) inhibitor (e.g. ribociclib, abemaciclib) use are allowed and must have been completed >= 2 weeks prior to C1D1; failure to adhere to this washout guideline will result in a protocol violation
Patients may have had prior systemic therapy in the adjuvant setting; however this adjuvant treatment must not have included a CTLA4 or PD1 pathway blocking antibody or a BRAF/MEK inhibitor; also, patients may not have had any prior systemic treatment for advanced (measurable metastatic) disease
EFTs: no more than two prior chemotherapy-containing lines in the metastatic/recurrent setting.
Patients must have received irinotecan therapy in the metastatic setting; there are no limitation on number of prior therapies in the metastatic setting
Prior therapy is allowed as follows:\r\n* Platinum chemotherapy in the adjuvant setting is allowed, if the last platinum dose was > 12 months before identification of metastatic disease; platinum-based chemotherapy in the metastatic setting is not permitted\r\n* History of prior anthracycline (e.g. doxorubicin, epirubicin) and taxane-based (e.g. paclitaxel, docetaxel) chemotherapy in the neo-adjuvant / adjuvant or metastatic setting is preferred, but not required\r\n* Patients with hormone receptor-positive (estrogen and/or progesterone receptor-positive) disease must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy; endocrine therapy must have been completed at least 7 days before study treatment\r\n* Prior radiation is allowed; radiation therapy must have been completed at least 21 days before study treatment\r\n* Prior treatment with Food and Drug Administration (FDA) approved or investigational biologics (other than PARP inhibitors) and novel molecularly targeted therapies, including oral or IV formulations, shall not exclude patients from participation\r\n* For agents with ambiguous categorization, final determination of patient eligibility will be made by the protocol chair prior to enrollment\r\n* Prior PARP inhibitor use is not allowed for this study
Received =< four (4) prior chemotherapy regimens in the metastatic setting
Any number of prior lines of therapy are allowed\r\n* Prior platinum based therapy is allowed in the following settings:\r\n** Treatment in the neoadjuvant and/or adjuvant setting without clear progression of disease\r\n** Treatment in the metastatic setting without clear progression of disease
Prior treatment specifics:\r\n* Participants must have radiological or objective evidence of progression to a CDK4/6 inhibitor regimen in the metastatic setting AND relapse/progression on an nonsteroidal anti-inflammatory drug (NSAI) (defined as either relapsed =< 12 months after completing adjuvant NSAI or progressed through an NSAI for metastatic or locally advanced breast cancer)\r\n* Participants may have received any number of previous endocrine/hormonal lines of therapy in the metastatic setting, as long none of them were exemestane-based and the last dose is >= 14 days prior to registration\r\n* Participants may have received any CDK4/6 inhibitor (i.e. palbociclib, ribociclib, abemacicliclib, etc) as long as the last dose is >= 14 days prior to registration\r\n* Participants may have received up to one prior chemotherapy line for advanced breast cancer as long as the last dose is >= 21 days prior to registration\r\n* Participants may have received prior biologic treatments or investigational drugs as long as the last dose is >= 21 days prior to registration\r\n* Participants may have received radiotherapy for palliative purposes but must not be experiencing > grade 1 treatment related toxicities and have completed treatment >= 14 days prior to registration
Participants who have received prior treatment with exemestane in the metastatic setting or who have recurred within 12 months of adjuvant exemestane
SAFETY RUN-IN: Patients received up to 2 prior regimens for their disease in the metastatic setting
Patients with only non-measurable bone lesions must have disease progression based on PCWG3 with 2 or more new lesions or have prostate-specific antigen (PSA) progression before enrollment. Arm 4: Patients with extensive-stage disease small cell lung cancer (SCLC) must meet the following criterion: i. Patients received ? 2 prior lines of therapy. Arm 5: Patients with HER2-negative gastric or gastroesophageal junction cancer must meet the following criterion: i. Patients received ? 2 prior lines of therapy. Arm 6: Patients with locally advanced or metastatic urothelial (muscle-invasive bladder, ureter, urethra or renal pelvis) cancer must meet the following criterion: i. Patients received ? 2 prior lines of therapy in the advanced or metastatic disease setting. ii. Patients must have received prior platinum-based systemic chemotherapy. Arm 7: Patients with advanced or metastatic pancreatic adenocarcinoma must meet the following criteria: i. Patients must have received at least one line of platinum containing regimens in either an advanced or metastatic setting, unless the patient has known deleterious germline or somatic BRCA1/2 mutation prior to being screened (in which case they can be considered for the study if the patient has never received platinum-containing regimen), AND ii. Patients received ? 1 prior lines of therapy in the advanced or metastatic disease setting. Arm 8: Patients with advanced or metastatic solid tumor malignancies must meet the following criterion: i. Patients with at least 1 prior platinum-containing treatment in any treatment setting.
Cohort A:\r\n* Prior treatment with at least one regimen containing trastuzumab and taxane\r\n* No prior treatment with T-DM1 that was discontinued due to disease progression or toxicity\r\n* No more than 4 prior lines of therapy in the metastatic setting
No prior therapies (except for anti-estrogen therapy) are allowed for the treatment of the newly diagnosed metastatic breast cancer; patients are allowed to have had prior chemotherapy for breast cancer in the adjuvant setting for at least 12 months prior to enrollment into this study; patients with a prior diagnosis of malignancy treated >= 5 years ago are eligible, provided that they have not received prior nab-paclitaxel as part of their prior treatment regimen, and that they meet all eligibility criteria
Patients with NSCLC must have predominant squamous histology. Patients must have received prior therapy with a platinum-based treatment and a checkpoint inhibitor (CPI), if eligible, and should have received no more than 2 systemic regimens in the locally advanced or metastatic setting.
Patients with SCCHN must have received prior therapy with a platinum-based regimen and a checkpoint inhibitor (CPI), if eligible, and should have received no more than 2 systemic regimens in the recurrent/metastatic setting.
Have received no more than 2 prior lines of therapy (maintenance therapy given in the metastatic setting will not be considered a separate regimen). Generally, treatments that are separated by an event of progression are considered different regimens.
Prior therapy for breast cancer in the advanced/metastatic setting must have included at least:
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 1st line or 2nd line systemic therapy in the metastatic setting for no more than 28 days and without clinical progression prior to the initiation of the study drug therapy are allowed to enroll on the study as their 1st line or 2nd line therapy, respectively
No prior systemic therapy in the metastatic or advanced setting
Prior cetuximab is allowed in the adjuvant but not in the metastatic setting, but must have been completed at least 6 months before starting this trial
Prior exposure to panitumumab in any setting
No more than 3 lines of chemotherapy in the metastatic setting.
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.
Have received at least 2 prior lines of anti-HER2 directed therapy in the metastatic setting, or in case of having received (neo)adjuvant pertuzumab, at least 1 prior line of anti-HER2 directed therapy in the metastatic setting. In either case, patients must have received prior treatment with pertuzumab, in the (neo)adjuvant or metastatic setting. Prior radiotherapy, hormonal therapies, and other anti-HER2 therapies are allowed.
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.
Must have received 4 or more prior lines or therapy in the metastatic setting
Treatment with chemotherapy within 28 days of registration including subjects who received more than 2 chemotherapy regimens in the metastatic setting at any time prior to registration
Patients must have had two or more lines of prior therapy (chemo or hormonal) in the metastatic setting
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
Histologically or cytologically confirmed metastatic or unresectable CRC that is relapsed, refractory, or progressive following at least 2 prior systemic regimens in the metastatic setting.
Both patients with stage IV and patients with recurrent disease after progression must have had at least 1 line of standard systemic therapy in the advanced/metastatic setting; a. patients with HER2-positive disease must have had at least 2 lines of anti-HER2 therapy, including Perjeta and Kadcyla in the metastatic setting; b. prior eribulin treatment is allowed
Received one or more prior therapies for TNBC or inflammatory breast cancer in the metastatic setting, and prior treatment (metastatic or (neo) adjuvant) must have included a prior taxane and/or anthracycline-based therapy.
More than 3 previous lines of therapy in the metastatic setting.
Prior chemotherapy, hormonal and radiation therapy administered in the adjuvant setting will be allowed
Any number of prior systemic treatment regimen in the advanced/metastatic setting is allowed (cytokine, anti-angiogenic, mTOR inhibitor or clinical trial) including previously untreated patients
Prior therapies:\r\n* Patients must have previously received an aromatase inhibitor in the adjuvant, neo-adjuvant or metastatic setting\r\n* The minimum duration of aromatase inhibitor (AI) in the adjuvant setting is 2 years\r\n* There is no minimum duration of AI in the metastatic setting or neoadjuvant setting\r\n* Patients may have been previously treated with a CDK 4/6 inhibitor or mTOR inhibitor or other investigational agent in addition to an aromatase inhibitor\r\n* Prior treatment with tamoxifen is allowed in the adjuvant setting provided that it was followed by a minimum of 2 years of an AI
Prior therapy exclusions:\r\n* Prior therapy with fulvestrant\r\n* Prior therapy with tamoxifen in the metastatic setting\r\n* More than 3 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 1st line systemic therapy for recurrent IBC; NOTE: Patients must not have received chemotherapy in the metastatic setting, but adjuvant treatment after surgery is acceptable
Prior treatment\r\n* No more than two prior chemotherapy regimens in the metastatic setting\r\n* Prior treatment with fulvestrant in the metastatic setting is required, except for patients with a history of ER-negative metastatic breast cancer\r\n* Unlimited prior endocrine therapy regimens in the metastatic setting are allowed\r\n* No prior treatment with an aurora Kinase inhibitor (either an aurora A or pan-aurora kinase inhibitor)
Have previously received prior treatment with at least 1 but no more than 3 chemotherapy regimens in the metastatic setting.
Patients must satisfy the following criteria for prior therapy:\r\n* Progressed on and following at least 6 months of combined treatment with palbociclib and AI therapy for advanced/metastatic breast cancer, and be able and willing to receive additional palbociclib treatment; palbociclib and AI must be the most recently received treatment prior to enrollment; up to one (1) prior line of chemotherapy for advanced/metastatic disease is allowed in addition to any number of prior lines of endocrine therapy\r\n* No prior treatment with fulvestrant, everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway in the metastatic setting; use of these agents in the neoadjuvant and/or adjuvant settings is permitted\r\n* Patients receiving bisphosphonate therapy prior to registration may continue at the same intervals used prior to study registration
Prior chemotherapy in the adjuvant setting is allowed
Patients must have had =< 3 prior therapies in the metastatic setting (not including chemotherapy given as maintenance therapy)
Metastatic colorectal cancer patients \r\n* Patient must have received a minimum of 1 systemic therapy in the metastatic setting
Prior trastuzumab use in the adjuvant or metastatic setting
> 2 lines of prior chemotherapy in the metastatic setting
Any number of prior lines of chemotherapy in the metastatic setting is allowed
Patients must have received at least one, but not more than three, systemic regimens for treatment of metastatic soft tissue sarcoma; patients must have had a prior anthracycline in either the adjuvant or metastatic setting unless medically inappropriate for the patient
Patients must have had at least 2 lines of anti-HER2 directed therapies either in the metastatic or early-stage disease 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 2 lines of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from colorectal cancer who received no more than 3 lines of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from gastroesophageal cancer who received no more than 1 line of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from biliary tract cancer who received no more than 1 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 < 3 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 1 line of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from gastroesophageal cancer who received no more than 1 line of prior therapy in the metastatic setting\r\n* NOTE: No prior exposure to any irinotecan in the metastatic setting will be allowed
Received no more than one prior regimen of chemotherapy in the metastatic setting
No prior systemic chemotherapy treatment in the metastatic setting
Patients may not have had a prior anti-angiogenic agent in the recurrent setting; prior use of bevacizumab in the upfront or upfront maintenance setting is allowed
Patients must have received at least one prior line of chemotherapy, for ULMS (either in the adjuvant or metastatic setting)
At least one prior systematic therapy in the metastatic setting
PRE-MENOPAUSAL ELIGIBILITY: \r\n* Premenopausal women who received adjuvant aromatase inhibitor and ovarian suppression (AI + OS) in the adjuvant setting and completed at least 12 months of hormonal therapy\r\n* Pre-menopausal women with de novo metastatic disease are eligible if they have had no prior endocrine therapy\r\n* Premenopausal women who have not received tamoxifen in the metastatic setting, but have received up to two lines of chemotherapy
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
Patient has received tamoxifen in the metastatic setting (for more than 30 days) or has progressed while on tamoxifen in the adjuvant setting
Patients must have received at least 1 chemotherapy regimens in the setting of metastatic disease
All patients should have received at least one line of chemotherapy in either the advanced or adjuvant setting and hormonal therapy (where appropriate)
At least one prior regimen of chemotherapy in the setting of metastatic breast cancer; no upper limit on the number of prior endocrine regimens for metastatic breast cancer, however no more than 6 chemotherapeutic regimens may have been given in the metastatic setting
Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ALK inhibitor therapy allowed).
Disease progression after crizotinib only. No prior chemotherapy is allowed in the metastatic disease setting.
Disease progression after crizotinib and 1 or 2 prior regimens of chemotherapy in the metastatic disease setting.
Treatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ROS inhibitor therapy).
Subjects may have had any number of prior chemotherapy, endocrine therapy, immunologic, or biologic regimens for metastatic breast cancer; treatment with prior platinum compounds (except cisplatin) is allowed as long as it has been 6 months or more since exposure to prior platinum; prior cisplatin treatment is allowed IF it was given in the adjuvant setting
Women must have received ? 1 prior hormonal treatment(s) in the metastatic or adjuvant setting. If the most recent hormonal treatment was in the metastatic setting, duration of response (tumor regression or stabilization of disease) to this specific course of therapy must be ? 6 months. If the most recent hormonal treatment was in the adjuvant setting, duration of response (disease free) to this specific course of therapy must be ? 3 years
Part B: Subject must not have received any prior lines of chemotherapy in the metastatic setting (prior treatment with immunotherapy is allowed).
No more than 2 prior chemotherapies in the advanced or metastatic setting
Prior treatment\r\n* No more than two prior chemotherapy regimens in the metastatic setting\r\n* Prior treatment with an aromatase inhibitor (either anastrozole, letrozole or exemestane), either in the adjuvant or metastatic setting is required\r\n* Unlimited prior endocrine regimens in the metastatic setting, which may have included an everolimus or cyclin dependent kinase (CDK) 4/6 inhibitor (such as palbociclib, abemaciclib or ribociclib) containing regimen\r\n* Prior tamoxifen treatment is allowed in the adjuvant setting, but patients must not have experienced relapse within 1 year of stopping tamoxifen\r\n* No prior treatment with tamoxifen in the metastatic setting\r\n* No prior treatment with endoxifen\r\n* Patients who have not fully recovered from acute, reversible effects of prior therapy regardless of interval since last treatment are not eligible to participate in this study\r\n** EXCEPTION: neuropathies-if grade 2 neuropathies have been stable for at least 3 months since completion of prior treatment patient is eligible
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-398 with 5-FU and leucovorin) must have failed one prior line of gemcitabine-based therapy with or without BBI608 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 > 6 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.
Randomized Phase 2 Dose Expansion - Individuals may have disease progression during treatment or within 12 months of completion of endocrine therapy (tamoxifen, and/or AI) in the adjuvant setting, or disease progression during treatment with endocrine therapy (tamoxifen, AI or CDK4/6 inhibitor plus AI) for advanced/metastatic disease. Individuals may have had unlimited prior hormonal therapy, but must be naive to fulvestrant in the metastatic setting. A total of 2 prior chemotherapies are allowed, however, only one for metastatic disease is permitted.
For Cohort 2: had prior systemic therapy in the advanced disease setting
Previous treatment with any systemic antineoplastic therapy in the advanced setting (NSCLC stage IIIB or IV. Patients who received only one cycle of antineoplastic therapy in the advanced setting are allowed).
Received more than 3 prior systemic treatment regimens with chemotherapy , hormonal, or immunotherapy in the metastatic setting or received more than 1 prior chemotherapeutic regimen in the metastatic setting
Prior treatment with standard first line therapy in the metastatic setting
The patient must have received at least 1 and no more than 2 prior lines of treatment in the metastatic setting.
Have received prior treatment with at least 2 chemotherapy regimens, of which at least 1 but no more than 2 have been administered in the metastatic setting.
Subject has received > 1 prior line of chemotherapy in the metastatic setting
Patients may have received but may not have progressed on prior anti-angiogenic therapy in the upfront 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 > 1 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 1 prior line of chemotherapy in the adjuvant and/or metastatic setting, but not more than 2 regimens in the metastatic setting
Unlimited number of lines of endocrine therapy and one line of cytotoxic chemotherapy in the metastatic setting (Phase II)
Patients may have received 1-3 prior systemic therapies in the metastatic setting.
Participants must have had prior trastuzumab therapy (either in the adjuvant or metastatic setting)
Must have had treatment with at least 2 but no more than 3 previous regimens in the metastatic setting. Previous treatment must have included an anthracycline and taxane in either the adjuvant or metastatic setting.
Patients should not have been previously treated with cytotoxic drugs and immunotherapeutic agents for unresectable stage III or stage IV disease; prior ipilimumab in metastatic setting is not allowed; prior therapy may include one line of targeted therapy for metastatic disease i.e. v-raf murine sarcoma viral oncogene homolog B (BRAF) or mitogen-activated protein kinase kinase (MEK) inhibitor; at least 3 weeks should have passed since the last dose of prior adjuvant interferon therapy and prior targeted therapies, and all previous therapy related toxicities should have resolved before starting study treatment; prior adjuvant interferon is permitted; prior cytotoxic therapy in adjuvant or metastatic setting is not allowed; prior ipilimumab in adjuvant setting is not allowed; prior adjuvant therapy with targeted therapy including but not limited to B-RAF, MEK inhibitors etc. is allowed; prior palliative radiation therapy for metastatic melanoma is permitted provided the patient has unirradiated metastatic sites for response evaluation and has fully recovered from its toxicity
Any number of prior endocrine therapies in the metastatic setting are allowed. The patient must not have received any prior chemotherapy agents in the metastatic setting. Prior treatment with adjuvant docetaxel or paclitaxel is allowed if disease relapse occurred greater than 12 months from the completion of adjuvant therapy.
Patients with ER and/or PR- positive/ HER2 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 1 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/ HER2-amplified invasive mammary carcinoma must have had at least one line of HER2-targeted therapy in the metastatic setting, or be diagnosed with metastatic breast cancer during or within 1 year of adjuvant HER2-targeted therapy; there is no limit on lines of prior HER2-targeted treatments in the metastatic setting
Received 1 or 2 prior anti-angiogenic therapy regimens in advanced or metastatic setting
No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting, and evidence of progression on or after last treatment regimen received and within 6 months of enrollment
Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed
Any number of previous chemotherapy regimens (except those containing TMZ or dacarbazine [DTIC]) in the metastatic setting are allowed as long as >= 4 weeks have elapsed from last treatment
Prior taxane therapy in the adjuvant or metastatic setting is allowed
Patients who have received other agents that modulate or downregulate the estrogen receptor (e.g. raloxifene, fulvestrant) in the adjuvant setting are eligible if they were on treatment for at least 6 months prior to disease progression in the locally advanced or 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, 1-2 prior lines of endocrine therapy are allowed
Prior treatments:\r\n* Subjects should have received at least two approved HER2-targeted agents (trastuzumab, pertuzumab, or TDM-1) in the course of their disease\r\n* Subjects should have had at least 1 line of prior HER2-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 2 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
PRIOR THERAPY PHASE I and PHASE I-T:\r\n* Prior chemotherapy for ovarian cancer patients must have included a first-line platinum-based regimen with or without intravenous consolidation chemotherapy\r\n* Breast cancer patients must have recurred post both an Adriamycin- and taxane-containing regimen\r\n* Prior hormonal-based therapy for ovarian, primary peritoneal serous, fallopian tube cancer, or breast cancer is acceptable\r\n* Patients may not have had a prior PAR polymerase (PARP)-inhibitor in the recurrent or metastatic setting; prior treatment with BSI-201 (iniparib) is allowed\r\n* Patients may not have had a prior anti-angiogenic agent in the recurrent or metastatic setting
Received more than 2 prior regimens for advanced or metastatic disease (not including hormonal therapy in the metastatic setting or neoadjuvant or adjuvant therapies)
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
Patients may not have received more than 2 prior systemic treatment regimens for distant metastatic disease. The following prior therapy is permitted in either the adjuvant or metastatic disease setting, provided treatment is discontinued at least 4 weeks prior to initiating study treatment:
No more than two prior chemotherapy regimens administered for the treatment of pancreatic cancer in the adjuvant or advanced/metastatic setting
Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 6 months prior to study entry)
Prior taxanes in the neoadjuvant or adjuvant setting with progression occurring within 6 months of completion of taxane therapy; or any taxanes in the metastatic setting.
More than one prior chemotherapy regimen administered 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 1 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 1 prior line of endocrine therapy in the metastatic setting
Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting
Part I: Postmenopausal women with locally ABC or MBC whose disease relapsed during treatment with (or within 6 months after discontinuation of) an AI in the adjuvant setting or progressed during treatment with an AI in the metastatic setting.
For participants in the second NSCLC cohort expansion, not more than two prior regimens in the metastatic setting
At least one line of endocrine therapy in the metastatic setting
Must have a biopsy in the metastatic setting with HER2 expression of 1+ or 2+ by IHC
The participant has received more than 2 prior regimens of systemic therapy in the metastatic setting
Participants must have already received or been intolerant to at least two lines of hormonal therapies (including the adjuvant or metastatic setting) or be appropriate candidates for chemotherapy
Patients must have at least 1 standard treatment regimen in the advanced, recurrent or metastatic setting
Have received prior chemotherapy in the metastatic castration-resistant setting (prior chemotherapy in the hormone-sensitive setting is allowed provided last dose was at least 6 months prior to study entry)
Part 3, Dose exploration, CRC subjects can be treatment naïve but should not have received more than one line of systemic therapy in the recurrent/metastatic setting.
Prior treatment of pancreatic cancer in the metastatic setting (or locally advanced setting) with surgery (placement of stent is allowed), radiotherapy, chemotherapy or investigational therapy
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.
Patients with adenocarcinoma arising from the esophagus, gastroesophageal junction, or stomach must also meet the following criteria: a. Must have received prior treatment with a platinum/fluoropyrimidine-based therapy with or without an anthracycline in the metastatic setting; or, in the adjuvant setting if recurrence occurred within 6 months of completing systemic adjuvant treatment; b. Patients with HER2 positive tumors must have had prior treatment with a Her2 inhibitor (e.g. trastuzumab or lapatinib); c. Patients who have received prior taxane therapy may be enrolled.
No prior treatment with carboplatin in the metastatic setting; carboplatin in neoadjuvant/adjuvant setting may be allowed if prior treatment with carboplatin was completed at least one year prior to initiation of this study and after discussion with the study chair
For adjuvant setting patients: Metastatic Disease (M+) prior to surgery
For salvage setting patients: Metastatic Disease at PSA rise
For adjuvant setting patients, any treatment received after surgery
History cancer with no limitation on prior lines of therapy in the metastatic setting
No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting
Part C: must have previously received prior treatment with at least 1 but no more than 2 chemotherapy regimens in the metastatic setting