Patients must not have had history of severe toxicity and intolerance to or hypersensitivity to irinotecan or any other study drug; patients must not have had a severe infusion-related reaction during any prior therapy with pertuzumab or trastuzumab
Prior therapy - prior trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (T-DM1) are allowed; patients who have received prior therapy with taselisib (GDC-0032) or BYL-719 are excluded; there is no limit on the number of prior lines of therapy
Patients must have received at least two lines of HER2-directed therapy in the inoperable locally advanced and/or metastatic setting; prior therapy for inoperable locally advanced/metastatic disease should include trastuzumab plus pertuzumab as well as ado-trastuzumab; pertuzumab and ado-trastuzumab should have been previously used, unless for reasons that include, but are not limited, to the following: intolerance to pertuzumab and/or ado-trastuzumab, medical contraindication, regimen declined by patient, treating investigator discretion, or medical insurance coverage issues which prevented administration of pertuzumab or ado-trastuzumab; these reasons must be reviewed with the study chairs and documented in the medical record and care report form; patients who relapse within 12 months of completing neoadjuvant/adjuvant pertuzumab or ado-trastuzumab would be considered as having progressed on that regimen
History of ejection fraction drop below the lower limit of normal with trastuzumab and/or pertuzumab.
One of the following must be true:\r\n* Distant disease progression during administration of combination therapy with taxane based chemotherapy and anti-HER2 therapy (trastuzumab or pertuzumab) for metastatic disease; note: patients who began treatment with this combination and discontinued taxane-based chemotherapy due to intolerability before distant disease progression are eligible\r\n* Distant disease progression during administration or within 180 days of discontinuing combination therapy with taxane based chemotherapy and anti-HER2 therapy (trastuzumab or pertuzumab) in the adjuvant disease; note: patients who began treatment with this combination and discontinued taxane-based chemotherapy due to intolerability before distant disease progression are eligible\r\n* For patient who received taxane based chemotherapy and anti-HER2 therapy (trastuzumab or pertuzumab) in the neo-adjuvant setting and underwent surgical resection of primary breast disease: distant disease progression during or within 180 days of discontinuing anti-HER2 therapy (trastuzumab or pertuzumab) in the adjuvant setting
Patients must not have received systemic therapy within 2 weeks of initiating palbociclib; NOTE: For the HER2-positive cohort, patients on trastuzumab can remain on the drug; no break or washout period required; however, lapatinib, ado-trastuzumab-emtansine, and pertuzumab are prohibited and a minimum wash out period of 2 weeks is required
For Part H: (abemaciclib + trastuzumab + pertuzumab): The participant must have received at least 1 chemotherapy regimen for metastatic disease. The participant may be receiving ongoing therapy with trastuzumab and/or pertuzumab at the time of study entry. The participant must have an estimated left ventricular ejection fraction (LVEF) within the normal range by either echocardiogram or multigated acquisition (MUGA) scan.
Known intolerance to trastuzumab or pertuzumab or atezolizumab
Patients must have previous treatment with ado-trastuzumab emtansine (Kadcyla, T-DM1) in any setting. Patients must have previously received trastuzumab and pertuzumab in the metastatic setting or within 12 months of neoadjuvant/adjuvant treatment.
If applicable, use of contraception methods or abstinence as defined by the protocol Study-Drug Specific Inclusion Criteria: Trastuzumab plus Pertuzumab
Eligible for another actively accruing Roche/Genentech-sponsored interventional clinical trial Study-Drug Specific Exclusion Criteria: Trastuzumab plus Pertuzumab
HER2-overexpressing (3+ by IHC) or HER2 2+ and FISH positive breast cancer must have progressed after prior treatment with trastuzumab, pertuzumab, and T?DM1
HER2 IHC 3+ or IHC 2+/FISH+ breast cancer patients who have received prior therapy with trastuzumab, pertuzumab, and T-DM1, at least 1 and no more than 3 prior systemic chemotherapy regimens
Trastuzumab, pertuzumab, lapatinib, or T?DM1 within 3 weeks before first ZW25 dosing
PART I: Naive to trastuzumab (Herceptin), pertuzumab (Perjeta) and lapatinib (Tykerb), ado-trastuzumab emtansine (Kadcyla) or other HER2-directed therapies
PART II: Recurrent or progressive metastatic disease after standard of care HER2-targeted therapies i.e. trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), ado-trastuzumab emtansine (TDM1) (Kadcyla) or other HER2-directed therapies
Medically and surgically appropriate to undergo neoadjuvant chemotherapy with TCH-P Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), Perjeta (pertuzumab) regimen followed by standard of care local therapy as determined by their treating physician
Must have received prior trastuzumab, pertuzumab, and T-DM1
Prior therapy with other HER2 targeted agents is not required, such as T-DM1 or pertuzumab
HER2 positive and ER and PR negative tumors: must have failed at least 2 regimens containing at least two anti-HER2 agents (e.g. trastuzumab and pertuzumab).
Planned neoadjuvant therapy with six cycles of combined pertuzumab, trastuzumab and chemotherapy
Participants who are not considered candidates for pertuzumab + trastuzumab + chemotherapy
Minimum number of prior treatments required given standard nab-paclitaxel dosing:\r\n* If HER2 negative: none; Note: Subjects with hormone-receptor positive tumors (estrogen receptor positive [ER+] and/or progesterone receptor positive [PR+]) must have failed available appropriate lines of hormonal therapy (eg, ovarian suppression or ablation, selective estrogen receptor modulators, aromatase inhibitors, estrogen receptor antagonists, etc), unless intolerant to hormonal therapy or hormonal therapy is not considered to be clinically appropriate\r\n* If HER2 positive: two prior regimens containing HER2 targeted therapies in the inoperable locally advanced and/or metastatic setting; prior therapy for inoperable locally advanced/metastatic disease should include trastuzumab plus pertuzumab as well as ado-trastuzumab; pertuzumab and ado-trastuzumab must have been previously used, unless for reasons that include, but are not limited, to the following: intolerance to pertuzumab and/or ado-trastuzumab, medical contraindication, regimen declined by patient, treating investigator discretion, or medical insurance coverage issues which prevented administration of pertuzumab or ado-trastuzumab; these reasons must be reviewed with the study chairs and documented in the medical record and care report form; patients who relapse within 12 months of completing neoadjuvant/adjuvant pertuzumab or ado-trastuzumab would be considered as having progressed on that regimen\r\n* There is no maximum number of prior treatments allowed in the metastatic setting
Patients must have had anti-HER2 based therapy for metastatic disease (which may include trastuzumab and pertuzumab either sequentially or in combination).
Subjects must have received trastuzumab in the metastatic setting and experienced disease progression on this drug; any number of prior therapies is permitted; prior therapy with other HER2 targeted agents (trastuzumab emtansine [TDM-1], pertuzumab, lapatinib) is allowed; the last dose of cytotoxic chemotherapy must have occurred >= 3 weeks prior to study registration; the last radiation therapy must have occurred >= 3 weeks prior to study registration
Intolerance to previous trastuzumab or pertuzumab therapy
Have progressed on at least one prior line of chemotherapy plus HER2 directed therapy such as trastuzumab and/or pertuzumab in the metastatic setting; trastuzumab emtansine (T-DM1) would count as a line of therapy and patients previously treated with T-DM1 are eligible
HER2+ patients must have received pertuzumab and TDM-1 (ado-trastuzumab emtansine) prior to trial enrollment; unless deemed ineligible for these therapies, and with the exceptions listed below:\r\n* Patients with metastatic breast cancer who have not received prior pertuzumab are eligible if: heavily pretreated prior to Food and Drug Administration (FDA) approval of pertuzumab (6/8/2012) for first-line treatment of HER2+ metastatic breast cancer (MBC)\r\n* Patients with metastatic breast cancer who have not received ado-trastuzumab emtansine are eligible if: heavily pretreated prior to FDA approval of ado-trastuzumab emtansine (2/22/2013) for the treatment of patients with HER2+ MBC who previously received trastuzumab and a taxane separately or in combination
Prior treatment with trastuzumab + pertuzumab (HP)-based or pertuzumab-based therapy in the neoadjuvant/adjuvant, unresectable, locally advanced, or metastatic setting
=< 3 prior chemotherapies in the metastatic setting; prior anthracycline, taxane, gemcitabine, and anti-HER2 agents (i.e. trastuzumab, pertuzumab, lapatinib, neratinib, TDM-1, etc.) are allowed; if patients received prior gemcitabine, it could not have been combined with pertuzumab; patients should have progression of disease on current therapy
History of prior >= G 3 hypersensitivity (HSR) or any toxicity to trastuzumab or pertuzumab that warranted permanent cessation of this agent
Prior treatment with pertuzumab, Lapatinib, and/or Trastuzumab emtansine is allowed; however, the last treatment for MBC must not include Trastuzumab in combination with pertuzumab.
Last treatment for metastatic disease including Trastuzumab in combination with pertuzumab
Prior treatment with trastuzumab and/or lapatinib or trastuzumab and pertuzumab in the neo-adjuvant or adjuvant setting is allowed but not required\r\n* Lapatininb has to be discontinued > 21 days before the initiation of the T+P study treatments; prior lapatinib in combination with hormonal therapy for treatment of MBC is allowed but not required as long as the other eligibility criteria are met
Participants must have received prior therapy with the following agents in any combination, and in setting (i.e., neoadjuvant, adjuvant, metastatic, etc.); these therapies do not need to be the most recent line of therapy\r\n* Trastuzumab\r\n* Pertuzumab\r\n* Ado-trastuzumab emtansine (T-DM1)
Patients must continue HER2-targeted monoclonal antibody therapy dosing per standard of care through the entire study period (one year)\r\n* HER2-targeted monoclonal antibody therapy is defined as either trastuzumab monotherapy, or trastuzumab and pertuzumab combination therapy administered per standard of care
Prior therapy - prior trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (T-DMI) are allowed; there is no limit on the number of prior lines of therapy
Participants must have received at least 1 line of chemotherapy for advanced or metastatic breast cancer and/or relapse/progressed while on or within 6 months of completion of neoadjuvant or adjuvant trastuzumab/pertuzumab; prior pertuzumab is allowed for Cohort B but not Cohort A
Patients must have progressed on, or be intolerant to pertuzumab in the LABC/MBC setting or had disease recurrence within 12 months of pertuzumab treatment in the neoadjuvant or adjuvant setting.
Patients must have been previously treated with trastuzumab in any setting (which may have been previously administered with or without pertuzumab)
Must have included trastuzumab, pertuzumab, and trastuzumab emtansine. Subjects starting initial systemic therapy for HER2-positive breast cancer prior to June 2012 are not required to have had pertuzumab
Receipt of trastuzumab, pertuzumab, or ado-trastuzumab emtansine within 4 weeks of scheduled dosing day 1.
No known hypersensitivity to trastuzumab or pertuzumab
Prior systemic cancer-directed treatments or investigational modalities =< 5 half lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from grade 2 or higher side effects of such therapy (except alopecia); an exception to this would be in patients receiving trastuzumab or pertuzumab immediately prior to trial enrollment, for whom the initial doses of trastuzumab and/or pertuzumab on study can be given within a time frame consistent with clinical guidelines and investigator discretion
Known allergic reaction to neratinib, pertuzumab, trastuzumab, paclitaxel, or any of their components
Prior treatment with trastuzumab, pertuzumab, and T-DM1, either alone or in combination, is required.
Any number of prior chemotherapies or biological therapies are allowed, patients are required to have prior treatment with pertuzumab and ado-trastuzumab emtansine with the exceptions listed below: \r\n* Metastatic patients who have not received prior pertuzumab are eligible if: heavily pretreated prior to Food and Drug Administration (FDA) approval of pertuzumab (08-June-2012) for first line treatment of HER2+ MBC\r\n* Metastatic patients who have not received ado-trastuzumab emtansine are eligible if: heavily pretreated prior to FDA approval of ado-trastuzumab emtansine (22-Feb-2013) for the treatment of patients with HER2+ MBC who previously received trastuzumab and a taxane, separately or in combination
No limit to prior therapies with last anti-cancer treatment >= 2 weeks from initiation of WBRT; please note: there is no washout period required for trastuzumab and pertuzumab
Continuation of trastuzumab and pertuzumab are allowed for those patients already on trastuzumab and pertuzumab therapy
Use of chemotherapy, trastuzumab, or pertuzumab within the past 3 weeks
No limit to prior therapies with last anti-cancer treatment >= 2 weeks from initiation of WBRT; please note: there is no washout period required for trastuzumab, pertuzumab for patients who have developed new parenchymal brain metastases while on these agents
Known hypersensitivity to trastuzumab or pertuzumab