Refractory disease to treatment with an mTOR inhibitor
Patient is INELIGIBLE if patient discontinued prior mTOR inhibitor due to toxicity
Participants who have received previous treatment with a mammalian target of rapamycin (mTOR) inhibitor
Participants may have received any number of prior therapies, from 0 to > 10; prior treatment with phosphatidylinositol 3 (PI3)-kinase or mTOR inhibitors is not permitted, unless they were given as adjuvant therapy without undue toxicity, and without suggestion of resistance to therapy
Patients may have received prior chemotherapy (excluding prior mTOR inhibitors)
Patients may NOT have received prior mTor inhibitors
Patients who have received prior treatment with an mTOR inhibitor
Previous treatment with CDK4/6 inhibitors or mTOR inhibitors
Patients who have been previously treated with an mTOR inhibitor
Patients with hypersensitivity to mTOR inhibitors or tamoxifen.
Previous treatment with an mTOR inhibitor
Patients previously exposed to, intolerant of, or ineligible for CDK inhibitors, mTOR inhibitors, and/or their combination
Patients who have received a prior mammalian target of rapamycin (mTOR) inhibitor
Patients who have received prior treatment with an mTOR inhibitor
Prior treatment with mTOR inhibitors or CDK 4/6 inhibitors in combination with endocrine therapy for treatment of metastatic disease
Prior treatment with histone deacetylase inhibitors or mammalian target of rapamycin (mTOR) inhibitors
For all stage 2 participants, no prior treatment with mTOR, PI3 kinase or Akt inhibitors; prior treatment with mTOR, PI3 kinase or Akt inhibitors allowed in stage 1 only
Prior treatment with mTOR inhibitor or other molecularly targeted therapy
No prior systemic chemotherapy for metastatic disease; one prior therapeutic regimen with a non-tyrosine kinase inhibitor, such as an mammalian target of rapamycin (mtor) inhibitor is allowed; patients who were randomized to placebo on an adjuvant study are eligible
Use of mammalian target of rapamycin (mTOR) inhibitors prior to transplant and as post-transplant immunosuppression
Concomitant oral mTOR inhibitor treatment
No more than 3 prior chemotherapy-inclusive regimens for locally advanced and/or metastatic disease (no limit on prior hormonal therapies or targeted anticancer therapies such as mechanistic target of rapamycin (mTOR) or CDK4/6 inhibitors, immune-oncology agents, tyrosine kinase inhibitors, or monoclonal antibodies against CTL4 or VEGF)
Previous treatment with exemestane or mTOR inhibitors* (Note: Patients with disease refractory to prior LEE011 are excluded for dose expansion Group 3 only).
Patients who have previously received everolimus, any another mTOR inhibitor or any agent targeting the PI3K/AKT/mTOR pathway.
Prior mTOR inhibitors for the treatment of cancer.
Pre-treatment with other mTOR inhibitors may be allowed and should be discussed with the medical monitor
Previous meningioma progression during treatment with other mTOR complex 1 (C1)/2 inhibitors (but not mTORC1 inhibitors such as everolimus or other rapalogues)
Prior mTOR inhibitor therapy within 4 weeks prior to first dose of study drug.
Prior failed treatment with mTOR inhibitors
Prior treatment with everolimus, other mammalian target of rapamycin (mTOR) inhibitors, or anti-VEGF drug (sunitinib, bevacizumab)
Previous treatment with mTOR inhibitors.
Known hypersensitivity to mTOR inhibitors, e.g., sirolimus (rapamycin).
Prior therapy with an Mammalian target of rapamycin (mTOR) inhibitor
Patients who have received prior treatment with an mTOR inhibitor or bevacizumab
Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks prior to randomization in the study.
Part B only: Prior treatment with agents targeting both mammalian target of rapamycin (mTOR) complexes (dual mammalian target of rapamycin complex 1/2 inhibitors) and/or PI3K/AKT pathways. However, prior treatment with isolated target of rapamycin complex 1 (TORC1) inhibitors (eg., rapalogs) is allowed in both parts of this study.
No prior mTOR inhibitors
Prior everolimus or pazopanib therapy; other mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors are allowed
EXPANSION COHORT ONLY: Prior mTOR pathway inhibitors or VEGF receptor inhibitor therapy
No prior therapy with an mTOR-pathway inhibitor
Prior treatment with histone deacetylase inhibitors or mammalian target of rapamycin (mTOR) inhibitors
Previous treatment with mTOR inhibitors, or exemestane for advanced disease.
Parts A and B only: Has received mTOR inhibitor(s) as their only prior treatment for ccRCC.
Prior use of histone deacetylases (HDAC) or mammalian target of rapamycin (mTOR) inhibitors
Prior treatment with an mTOR inhibitor.
Prior treatment with pan-histone deacetylases (HDAC) or mammalian target of rapamycin (mTOR) inhibitor
Prior treatment with trastuzumab or other HER2-directed therapies or with a mammalian target of rapamycin (mTOR) inhibitor within 12 months of study entry (when cancer was not definitely hormone refractory)
History of significant toxicity related to mTOR inhibitor requiring treatment discontinuation
Prior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitor
Use of systemic immunosuppressant agents including anti-metabolites, glucocorticoids, tumor necrosis factor (TNF) alpha antagonists, antibodies to interleukin (IL) 6 or IL6 receptor (R), calcineurin inhibitors, mammalian target of rapamycin (mTOR) antagonists
Patients may not have had prior treatment with mTOR, peptidase inhibitor 3, skin-derived (PI3) kinase or Akt inhibitors
Pre-treatment with other mTOR inhibitors may be allowed and should be discussed with the medical monitor
Prior treatment with mammalian target of rapamycin (mTOR) inhibitors will be allowed as long as the patient did not have >= grade 3 toxicity attributed to the mTOR inhibitor with prior therapy
Prior treatment with an mTOR inhibitor (including sirolimus) is allowed; however, patients with >= grade 3 toxicities with an mTOR inhibitor are excluded
Subjects with prior treatment with a mechanistic target of rapamycin (mTOR) are eligible
Non-clear cell histology: 0-3 prior systemic therapies and may include mTOR inhibitor
Patients must not be receiving or planning to receive trastuzumab; concurrent bisphosphonate therapy is allowed; patients must not have prior exposure to mechanistic target of rapamycin (serine/threonine kinase) (mTOR) inhibitors (rapamycin, everolimus, temsirolimus, deforolimus); patients must not have prior treatment with any investigational drug within the preceding 28 days and must not be planning to receive any other investigational drug for the duration of the study
Patients who have previously received temsirolimus, another mTOR inhibitor, or any other investigational agent
Patients who are receiving any other anticancer or investigational or/and anti-neoplastic therapies, including chemotherapy, immunotherapy, target therapy, biological response modifiers\r\n* Previous treatment with CDK4/6 inhibitors (such as PD-0332991, abemaciclib) and/or mTOR inhibitors (such as sirolimus, temsirolimus or everolimus)\r\n* Patients who are currently receiving treatment with agents that are known to cause corrected QT (QTc) prolongation or induce Torsades de Pointes\r\n* Known need for major surgery within 14 days of the first dose of ribociclib and everolimus; please note: gastrostomy, insertion of a gastrostomy (G) tube, ventriculo-peritoneal shunt, endoscopic ventriculostomy and central venous access are NOT considered major surgery
Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
Prior treatment with mTOR or TORC1/2 inhibitors (eg, rapamycin, temsirolimus, everolimus, deferolimus) is NOT allowed
Prior treatment with an mTOR inhibitor (including, but not limited to, everolimus, temsirolimus, sirolimus, and ridaforolimus)
Prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
Patients who have been previously treated with mTOR inhibitors such as everolimus and temsirolimus, or with c-MET inhibitors such as cabozantinib
Patients can have had prior treatment for RCC including prior surgery, radiation therapy, immunotherapy with interleukin (IL)-2 or interferon (but not anti-programmed cell death [PD]1 or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4]), target therapy with receptor tyrosine kinase (RTK) inhibitors/mammalian target of rapamycin (mTOR) inhibitors, such as sunitinib, sorafenib, pazopanib, axitinib, everolimus, and temsirolimus (but not bevacizumab) or chemotherapy
Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
TREATMENT: Patients who have received prior everolimus or other mechanistic target of rapamycin (mTOR) inhibitors or those with known intolerance or hypersensitivity to other rapamycin analogs (e.g., sirolimus, temsirolimus) would not be eligible to receive everolimus on study; if these patients have mutations of interest in pathways other than the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (pI3K) pathway, they will be eligible to receive agents based on that mutation
DOSE ESCALATION COHORT: Subjects who have received sirolimus, everolimus, temsirolimus, or any other agent for current malignancy that theoretically targets PI3K, AKT and / or mTOR
DOSE EXPANSION COHORT: Subjects who have received sirolimus, everolimus, temsirolimus, or any other agent for current malignancy that theoretically targets PI3K, AKT and / or mTOR
Prior treatment with everolimus other than in combination with hormonal therapy for treatment of breast cancer or prior treatment with another mammalian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus) for any indication
Prior treatment with an mammalian target of rapamycin (MTOR) inhibitor (including everolimus, sirolimus, temsirolimus)
Patients who have received prior treatment with a known mammalian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus, everolimus)
Patients who have received prior treatment with an mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)
For RCC, prior treatment with everolimus or temsirolimus
Prior treatment with mTOR inhibitors (everolimus or temsirolimus) or CB-839
Patients who have prior therapy with everolimus or any other mammalian target of rapamycin (mTOR) inhibitor
Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus).
Patients must not have prior exposure to mammalian target of rapamycin (mTOR) inhibitors (e.g. rapamycin, everolimus, sirolimus, temsirolimus, deforolimus)
Prior therapy with mTOR inhibitors, including sirolimus, temsirolimus, deforolimus within 6 months prior to enrollment
Patients who have received prior treatment with a mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)
Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
Prior therapy with mammalian target of rapamycin (mTOR) inhibitors (e.g. sirolimus, temsirolimus)
Patients who have received prior systemic therapy for their RCC with vascular endothelial growth factor (VEGF) pathway inhibitor (such as sunitinib, sorafenib, and bevacizumab) or with mammalian target of rapamycin (mTOR) inhibitors (such as sirolimus, temsirolimus, everolimus, or deforolimus)
Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus); patients who have received prior treatment with Navelbine within prior 12 months
Had any prior treatment with temsirolimus or mTOR inhibitor.
Previously received rapamycin or rapamycin analogs, including ridaforolimus, temsirolimus, or everolimus
Patients who have received prior treatment with an mTOR inhibitor (e.g. sirolimus, temsirolimus, everolimus)
Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
Patients who have received prior treatment with an mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)
Prior treatment with everolimus or another mammalian target of rapamycin (mTOR) inhibitor (temsirolimus)
Patients who received prior PI3K, AKT or mTOR inhibitors are not allowed
Prior treatment with pazopanib or any phosphoinositide 3-kinase (PI3K), mTOR, protein kinase B (AKT), or dual PI3K/mTOR complex (CREB regulated transcription coactivator [TORC]1/TORC2) inhibitors will be prohibited
Patient must NOT have had previous treatment with any PI3K or AKT inhibitor
Patients must not have any prior treatment with any PI3K inhibitor, or lenalidomide
Prior treatment with a phosphatidylinositol 3 (PI3)-kinase, v-akt murine thymoma viral oncogene homolog 1 (AKT) or mammalian target of rapamycin (mTOR) inhibitor in which the patient experienced a grade >= 3 drug-related adverse event or otherwise would be at increased risk for additional PI3K-related toxicity
Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor
Prior treatment with idelalisib, other selective PI3K? inhibitors, or a pan-PI3K inhibitor.
Prior exposure to agents specifically targeting both mammalian target of rapamycin (mTOR) complexes (dual target of rapamycin complex 1 [TORC1] + target of rapamycin complex 2 [TORC2] inhibitors) and/or phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) pathways
AZD5363 plus olaparib\r\n* Patients with solid tumors with PIK3CA or AKT mutations or other molecular aberrations leading to dysregulation of the PI3K/AKT pathway detected by NGS or RT-PCR in assays performed at a CLIA-certified laboratory:\r\n** activating mutations in PIK3CA, AKT1, AKT2, AKT3, ARID1A\r\n** other molecular aberrations leading to dysregulation of the PI3K/AKT pathway, for example phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1)\r\n** during the course of the study new information may emerge relating to molecular aberrations that dysregulate the PI3K/AKT pathway; patients whose tumors bear these aberrations can be included in the study
Previous therapy with GS-1101 (CAL-101), IPI-145 or any drug that specifically inhibits PI3K or mechanistic target of rapamycin (mTOR) within last 6 months
Prior treatment with everolimus, or any other specific or selective TORC1/PI3K/AKT inhibitor (eg, temsirolimus)
For Parts A, B, C, D, E, F, H: Have received prior therapy with a CDK4/6 inhibitor, Part G: Have received prior therapy with fulvestrant or any PI3K and/or mTOR inhibitor (including LY3023414); Part I: Have received prior treatment with abemaciclib in any setting.
Patients should be excluded if they have had prior treatment with the combination of a PI3K inhibitor and a PD-1 inhibitor
Prior treatment with approved or experimental therapeutic agents with known inhibition of the PI3K pathway, including PI3K inhibitors, AKT inhibitors, and mTOR inhibitors
Patients previously treated with hormonal therapy (tamoxifen, AI) or PI3K, AKT, dual PI3K/mTOR, TORC1/2, or mTORC1 inhibitors.
Prior treatment with PI3K-inhibitor
Part B6 only: Participants must have squamous NSCLC; documented evidence of an activating molecular aberration of the PI3K/mTOR pathway
Parts B3, B4, B5 & B6: No previous treatment with any PI3K and/or mTOR inhibitor
Intolerance to any previous treatment with any phosphatidylinositol-3-kinase (PI3K) and/or mammalian target of rapamycin (mTOR) inhibitor.
Prior therapy with a PI3K delta inhibitor
Prior treatment with a mechanistic target of rapamycin (mTOR) inhibitor or phosphoinositide 3-kinase (PI3K) inhibitor.
Has received prior therapy with a PI3K-inhibitor (prior therapy with a PI3K-inhibitor is allowed if it was discontinued for intolerance)
Prior treatment with idelalisib, other selective PI3K? inhibitors, or a pan PI3K inhibitor.
Prior treatment with PI3K/AKT inhibitors
Prior treatment with a selective PI3K? inhibitor or a pan PI3K inhibitor.
Previous treatment with phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (AKT), dual PI3K/ mammalian (or mechanistic) target of rapamycin (mTOR) inhibitors, target of rapamycin complex 1/2 (TORC1/2) inhibitors or TORC1 inhibitors.
Prior treatment with an mTOR, AKT, or PI3K inhibitor
Prior treatment with an mechanistic target of rapamycin (mTOR) inhibitor or phosphatidylinositol-3-Kinase (PI3K) inhibitor is allowed but not required
Prior use of PI3K or Akt inhibitors in the metastatic setting for the treatment of cancer; these include, but are not limited to: taselisib, GDC-0941, GDC-0980, BEZ235, BKM120, LY294002, PIK-75, TGX-221, XL147, XL765, SF1126, PX-866, D-87503, D-106669, GSK615, CAL101; patients who have received PI3K/Akt inhibitors previously for < 4 weeks will be eligible
Patients who are receiving or may receive future treatment with PI3K or TNFalpha inhibitors
Previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitor or fulvestrant
Patients who have received prior treatment with a PI3K inhibitor or have known hypersensitivity to Gedatolisib or its excipients
Part E: Prior treatment with a PI3K/mTOR inhibitor
Patient has any prior use of PI3K inhibitors.
Patient has received prior treatment with any PI3K inhibitors
Patients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitor
Prior therapy with a selective phosphoinositide 3-kinase (PI3K) inhibitor or other B-cell receptor targeting agents is allowed
Patients who have received prior treatment with a pan-selective PI3K inhibitor are not eligible
Subject has received previous treatment with a PI3K inhibitor; exceptions may be made for subjects who discontinued treatment with a previous PI3K inhibitor for reasons other than toxicity or progression and as long as it has been > 12 months since discontinuation of the previous PI3K inhibitor; this exception will require prior approval from the study PI at KUMC
Prior sensitivity or intolerance to PI3K inhibitors
Patients who have had prior therapy with GSK2141795 or any other PI3K/AKT/MTOR pathway inhibitor
Prior treatment with a PI3K or protein kinase B (AKT) inhibitor; patients previously treated with an mechanistic target of rapamycin (mTOR) inhibitor are eligible
PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have received prior docetaxel; patients must not have received therapy with a drug known to be either a mitogen-activated protein kinase (MEK) inhibitor or a phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTOR) pathway inhibitor
Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor (pre-treatment with CDK4/6 inhibitors is allowed)
Previous therapy with GS-1101 (CAL-101, Idelalisib), IPI-145 (Duvelisib), TGR-1202 or any drug that specifically inhibits PI3K/ mTOR (including temsirolimus, everolimus), AKT or BTK Inhibitor (including Ibrutinib) in last 6 months
Group A: Prior treatment with a selective phosphatidylinositol 3-kinase (PI3K) ? inhibitor (eg, idelalisib), a pan-PI3K inhibitor, or a BTK inhibitor (eg, ibrutinib).
Group B: Prior treatment with a selective PI3K? inhibitor (eg, idelalisib) or a pan PI3K inhibitor.
Prior therapy with obinutuzumab and/or chlorambucil or a PI3K delta inhibitor
Prior treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor, mammalian target of rapamycin (mTOR) inhibitor (e.g. everolimus), or protein kinase B (AKT) inhibitor
Group 3: Advanced solid tumors with PI3K pathway alterations (PIK3CA mutation or PTEN loss) after failure of at least one line of prior standard therapy or for whom no further standard therapy is indicated. Prior treatment may not include inhibitors of the PI3K pathway.
Prior therapy with agents that target Phosphatidylinositide 3-kinases (PI3K), Protein kinase B (AKT), or mechanistic target of rapamycin (mTOR). Participants with known hypersensitivity to everolimus or rapamycin derivatives are also excluded.
Prior treatment with PI3K? or Bcl-2 inhibitors.
Previous therapy with Akt, PI3K, and/or mTOR inhibitors
For Part D (abemaciclib + LY3023414): Any subtype. The participant must have received at least two, but not more than three prior therapies for advanced/metastatic NSCLC. The participant must not have received prior treatment with any phosphoinositide 3-kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibitor.
Prior treatment with any CDK inhibitor, fulvestrant, everolimus, or agent that inhibits the PI3K-mTOR pathway
Patients previously treated with ibrutinib or PI3K inhibitor
The patient has received prior treatment with a PI3K inhibitor, AKT inhibitor, or mechanistic target of rapamycin (serine/threonine kinase) (mTOR) inhibitor (e.g. rapamycin, MK2206, perifosine, etc.)
Prior treatment with apalutamide or phosphatidylinositol-3 kinase (PI3K)/mTOR pathway inhibitors
At least 4 weeks must have elapsed from the use of any investigational agent prior to beginning protocol therapy\r\n* Note: prior treatment with phosphatidylinositol 3 kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway inhibitors prohibited
Prior treatment with PI3K/mTOR pathway inhibitors
At least one prior therapy; prior autologous or allogeneic stem cell transplant is allowed; patients may not be on chronic immunosuppressive therapy for graft-versus-host disease (GVHD); patients who have received prior treatment with a pan-selective PI3K inhibitor are not eligible; however, prior therapy with a selective PI3K inhibitor, Bruton‘s tyrosine kinase inhibitor, or other B-cell receptor targeting agents is allowed
Patients with prior sensitivity or intolerance to PI3K inhibitors are not eligible for participation
Previous treatment with a PI3K inhibitor or BTK inhibitor
Patients must have NOT received any class of drugs targeted to the PI3K pathway (such has PI3K inhibitors or mechanistic target of rapamycin [mTOR] inhibitors) or RAS-ERK pathway for management of recurrent or persistent disease
Patients who received previous therapy with PI3K inhibitors or rapalogs will be allowed in the study if all other inclusion/exclusion criteria are met
Previous treatment with a PI3K inhibitor or BTK inhibitor.
Prior PI3K inhibitor or AKT inhibitor (patients previously treated with everolimus are eligible)
Prior therapy with a PI3K inhibitor; prior use of Akt or mammalian target of rapamycin (mTOR) inhibitors are allowed
Previous therapy with GS-1101 (CAL-101), IPI-145 or any drug that specifically inhibits the PI3K or mTOR pathway;
Prior treatment with PI3K inhibitors
Prior treatment with a PI3K inhibitor
Prior treatment with idelalisib, other selective PI3K? inhibitors, or a pan-PI3K inhibitor.
History of prior therapy with any phosphatidylinositol 3-kinase (PI3K) inhibitor (including idelalisib), or any anti-CD37 agent
Prior treatment with PI3K inhibitor(s)
Previous treatment with a PI3K or AKT inhibitor.
Progressive disease while previously receiving a PI3K inhibitor (e.g. GS-1101 [idelalisib], duvelisib) or a serious/severe AE related to PI3K inhibitor treatment
Prior treatment with a PI3K inhibitor or BTK inhibitor
Patient has received previous treatment with any AKT, mTOR inhibitors or PI3K pathway inhibitors;
Received prior treatment with Insulin-like Growth Factor 1 Receptor (IGF-1R) inhibitors, Phosphatidylinositol 3-Kinase (PI3K) inhibitors, or other experimental agents that target PI3K, Protein Kinase B (AKT), or Mammalian Target of Rapamycin (mTOR) pathway
Prior treatment with PI3K-inhibitors
Patients previously treated with an mTOR, AKT, or PI3K inhibitor (including but not limited to GDC-0941, GDC-0980, BEZ235, BKM120, LY294002, PIK-75, TGX-221, XL147, XL765, SF1126, PX-866, D-87503, D-106669, GSK615, CAL101, everolimus, temsirolimus, and ridaforolimus); for agents not listed, the study principal investigator (PI) or Co-PI will make a determination
Patients previously treated with an mammalian TOR (mTOR) or PI3K inhibitor
Prior cytotoxic chemotherapy, immunotherapy, a PI3K/AKT/mTOR agent (including TORC1 and TORC2 inhibitors), or RA 223 dichloride for the treatment of castration resistant prostate cancer (CRPC). Participants may have received docetaxel in the hormone-sensitive setting.
Subject must have received at least one BCR PI (ibrutinib, idelalisib, or other approved BTK or PI3K inhibitor) and/or venetoclax;
BTK/SYK/JAK/PI3K inhibitors
Patients must have known PI3K/mTOR pathway gene aberrations (from molecular profiling studies).
Prior treatment with a phosphoinositide -3 kinase (PI3K) inhibitor, Protein Kinase B Inhibitor is known as AKT inhibitor, or mammalian target of rapamycin (mTOR) inhibitor.
Part A: Intolerable AEs due to other PI3K inhibitors, dual PI3K and mTOR inhibitors or AKT inhibitors. Parts B, C, and D: Prior exposure to any of the following: pharmacological inhibitors of AKT, PI3K, or dual PI3K and mTOR kinase activity
The subject has previously been treated with a PI3K inhibitor and taken off treatment due to treatment related AEs.
Patient has received previous treatment with PI3K inhibitors, lomustine or carboplatin.
Prior treatment with phosphoinositide 3-kinase (PI3K) inhibitor
Prior treatment with a PI3K inhibitor
Patient has received previous treatment with PI3K inhibitors
Prior treatment with an Akt inhibitor (prior PI3K or mTOR inhibitors are allowed)
Previous treatment with PI3K inhibitors, AKT inhibitors or fulvestrant
Have received a selective phosphoinositide-3-kinase alpha isoform (PI3K-alpha) inhibitor
Prior treatment with fulvestrant, phosphoinositide 3-kinase (PI3K) inhibitor, or mechanistic target of rapamycin (mTOR) inhibitor for ABC or MBC
History of significant toxicity related to another phosphatidylinositol 3-kinase (PI3K) inhibitor or mammalian target of rapamycin (mTOR) inhibitor requiring treatment discontinuation
Prior treatment with PI3K inhibitor
Prior treatment with a dual mTORC1/mTORC2 inhibitor (CC-223 arms only) or BTK inhibitor (PCI-32765) (CC-292 arms only). [Prior treatment with rapamycin analogues, PI3K or AKT inhibitors, lenalidomide and rituximab are allowed].
Participants who are receiving any other investigational agents; history of prior PI3K, mTOR or CDK 4/6 inhibitor use for breast cancer
Planned treatment with agent targeting PI3K/mTOR pathway (either standard of care or investigational agent)
Prior therapy with mechanistic target of rapamycin (mTOR), phosphoinositide-3-kinase (PI3K), or dual PI3K-mTOR inhibitors, serine/threonine-specific protein kinase (AKT) inhibitors, or fulvestrant.
Discontinuation on prior BTK inhibitor or PI3K delta inhibitor due to adverse events within prior 9 months
Progression on prior BTK or PI3K delta inhibitor