Evaluation of IPI-549 Combined With Front-line Treatments in Pts. With Triple-Negative Breast Cancer or Renal Cell Carcinoma

Inclusion Criteria: 1. ≥18 years of age. 2. Have signed and dated an independent review board (IRB)/independent ethics committee (IEC) approved informed consent form (ICF) in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care. 3. Willing and able to comply with scheduled visits, treatment schedule, laboratory tests, fresh tumor biopsies, and all other protocol requirements. 4. At least 1 measurable disease lesion by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by RECIST v1.1 performed within 1 week prior to first dose. 5. Willing to undergo one pre-treatment core biopsy (unless archival tumor tissue is available within 3 months of first dose) and one on-treatment tumor biopsy, unless not safe or medically feasible. If the patient is unwilling to undergo biopsy, they may be eligible with approval of the medical monitor. 6. Evaluable tumor tissue (archived \[without time constraints\] or new biopsy) must be provided for biomarker analysis, which will include PD-L1 expression level using immunohistochemistry (IHC) to measure specific PD-L1 signals in tumor-infiltrating immune cells (ICs). Results are not required prior to start of study treatment. 7. Eastern Cooperative Oncology Group (ECOG) performance status ≤1. 8. Life expectancy ≥12 weeks. 9. Baseline laboratory values must meet the following criteria within 14 days of the first dose: 1. Adequate hematologic function, defined as white blood cell (WBC) count ≥2.0 × 109/L, absolute neutrophil count ≥1.5 × 109/L (without granulocyte colony-stimulating factor \[GCSF\] support within 2 weeks prior to Cycle 1, Day 1), lymphocyte count ≥0.5 × 109/L, hemoglobin ≥9.0 g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion), and platelet count ≥100 × 109/L (without transfusion within 2 weeks prior to Cycle 1, Day 1). 2. Calculated creatinine clearance ≥30 mL/min. 3. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) \<2.5 × upper limit of normal (ULN). ALT and AST ≤5 × ULN if documented liver metastasis. ALP ≤5 × ULN if documented bone or liver metastasis. 4. Total bilirubin ≤1.25 × ULN (unless elevated due to Gilbert's syndrome who can have total bilirubin \<3.0 mg/dL). 5. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN. This applies to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose. 6. Serum albumin \>2.5 g/dL 10. Women of childbearing potential (WOCBP) must have a negative serum or urine β human chorionic gonadotropin (βhCG) pregnancy test within 1 week before administration of study drug WOCBP is defined as any female who has ≥12 months of non-therapy induced amenorrhea or is surgically sterile. 11. Women must not be breastfeeding. 12. Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of study treatment, including 30 days after the last dose of IPI-549 and of nab-paclitaxel, or 6 months after the last dose of atezolizumab or bevacizumab, whichever is later. Male patients must refrain from donating sperm for these same periods. Male patients with a pregnant female partner must agree to remain abstinent or use a condom during the treatment period and for the duration of the pregnancy. Patients in Cohort A must meet the following additional criteria for inclusion: 1. Women with metastatic or locally advanced (not amenable to resection with curative intent), histologically documented TNBC, i.e., absence of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR) expression: 1. HER2 negativity defined as either of the following by local laboratory assessment 2. ER and PR negativity defined as \<1% of cells expressing hormonal receptors via IHC analysis 2. No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC. Radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy. Patients should be recovered from the effects of radiation. Prior chemotherapy (including taxanes) in the neoadjuvant or adjuvant setting is allowable if treatment was completed ≥12 months prior to randomization. Patients in Cohort B must meet the following additional criteria for inclusion: 1. Men or women with histologically documented unresectable advanced or metastatic RCC with clear-cell histology. 2. No prior treatment with active or experimental systemic agents, including treatment in the neoadjuvant or adjuvant setting. Prior radiotherapy is permitted but must not have been administered within 14 days of Cycle 1, Day 1. Exclusion Criteria: 1. WOCBP who are pregnant or breastfeeding. 2. Women with a positive pregnancy test at enrollment or prior to administration of study medication. 3. Any serious or uncontrolled medical disorder that, in the opinion of the Investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the patient to receive protocol therapy, or interfere with the interpretation of study results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome). 4. Any history of, or currently active, brain or leptomeningeal metastases. 5. Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina. Patients with a known left ventricular ejection fraction (LVEF) \<40% will be excluded. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF \<50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate. 6. Baseline QT interval corrected with Fridericia's method (QTcF) \>480 ms. 7. Major surgical procedure within 4 weeks prior to enrollment or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis. Placement of central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure and is therefore permitted. 8. Active tuberculosis. 9. Ongoing systemic bacterial, fungal, or viral infections at Screening. 10. Positive test for human immunodeficiency virus (HIV). 11. Active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 12. Dependence on continuous supplemental oxygen use. 13. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX®) are allowed. 14. Uncontrolled hypercalcemia (\>1.5 mmol/L ionized calcium or calcium \>12 mg/dL or corrected serum calcium \>ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy. Patients who are receiving denosumab must discontinue denosumab use and replace it with a bisphosphonate instead while on study. There is no required minimum washout period for denosumab. Patients who are receiving bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. 15. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells, or any of the study drug components. 16. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. 17. History of stroke, transient ischemic attack, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to Screening. 18. Other prior malignancy active within the previous 5 years except for local or organ confined early stage cancer that has been definitively treated with curative intent, does not require ongoing treatment, has no evidence of residual active disease, and has a negligible risk of recurrence and is therefore unlikely to interfere with the primary and secondary endpoints of the study, including response rate and safety. 19. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. 20. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 21. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. 22. Prior allogeneic stem cell or solid organ transplantation. 23. Administration of a live or attenuated vaccine within 4 weeks of first dose of study drug or anticipation that such a live or attenuated vaccine will be required during the study or within 5 months following the last dose of atezolizumab. 24. Prior therapy with experimental anti-tumor vaccines; any T cell co-stimulation or checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, including ipilimumab, or other medicines specifically targeting the T cell; or IPI-549. 25. Treatment with systemic immunostimulatory agents (including but not limited to interferons or IL-2) within 4 weeks or 5 half-lives of the drug (whichever is shorter) prior to enrollment. 26. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial. 27. Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization. 28. Administration of any of the following within 1 week prior to the administration of study drug: 1. Strong inhibitors or inducers of cytochrome P450 (CYP) 3A4, including grapefruit, grapefruit juice and herbal supplements. 2. Warfarin, phenytoin, or other substrates of CYP2C8 or CYP2C9 with a narrow therapeutic range. 3. P-glycoprotein (P-gp) inhibitors. 29. Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy). Patients in Cohort A are to be excluded from the study if they meet any of the following criteria: 1. Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>2 weeks prior to first dose of study treatment. 2. Uncontrolled tumor-related pain. 3. Known hypersensitivity to nab-paclitaxel or to any of the excipients. Patients in Cohort B are to be excluded from the study if they meet any of the following criteria: 1. Inadequately controlled hypertension (systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg or prior history of hypertensive crisis or hypertensive encephalopathy. 2. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1. 3. Evidence of bleeding diathesis or clinically significant coagulopathy (in the absence of therapeutic anticoagulation). 4. Current or recent (within 10 calendar days prior to Cycle 1, Day 1) use of dipyridamole, clopidogrel, or cilostazol. 5. History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 5 months prior to Cycle 1, Day 1. 6. Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding. 7. Evidence of abdominal free air not explained by paracentesis or recent surgical procedure. 8. Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture. 9. Proteinuria, as demonstrated by urine dipstick or \>1.0 g of protein in a 24-hour urine collection. All patients with ≥2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein.