AZD5153 in Patients With Relapsed or Refractory Solid Tumors, Including Lymphomas

Inclusion Criteria for all Patients: 1. Patient must be able to understand the nature of the study and provide a signed and dated, written informed consent prior to any study specific procedures, sampling or analyses. 2. Patients should have the ability and willingness to comply with the study and follow-up procedures. 3. Patients must have a solid tumor that is refractory to or intolerant of existing therapies known to provide clinical benefit for their clinical condition. 4. Age ≥ 18 5. Adequate organ function, determined by: * Absolute neutrophil count (ANC) ≥ 1.5 X 10\^9/L * Platelets ≥ 100 X 10\^9/L * Hemoglobin ≥ 9 g/dL * aPTT ≤1.5 x ULN * Total bilirubin ≤ 1.5 mg/dL * ALT and AST ≤ 2.5 x ULN if no liver involvement or ≤ 5 x ULN with liver involvement * Creatinine \<1.5 times ULN concurrent with creatinine clearance \>50 mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is \>1.5 times ULN 6. Normotensive or well controlled blood pressure (BP) (\<140/90), with or without current antihypertensive treatment. If there is a diagnosis or history of hypertension, patient must have adequately controlled BP on a maximum of 2 antihypertensive medications, as demonstrated by 2 BP measurements taken in the clinical setting by a medical professional within 1 week prior to enrollment. It is strongly recommended that patients who are on antihypertensive medications be followed by a cardiologist or a primary care physician for management of BP while on the study. Patients on a hypertensive medication must be willing and able to check and record twice daily BP readings for a minimum of 3 weeks. 7. ECOG performance status of 0-1 8. Life expectancy ≥ 3 months 9. Ejection fraction (EF) \> 50% 10. Patients must have the ability to swallow and retain oral medication 11. Toxicities from prior therapy greater than CTCAE Grade 1 have resolved with the exception of alopecia. Patients with Grade ≤ 2 neuropathy are eligible. 12. Male patients with female partners of child-bearing potential must be willing to use two forms of acceptable contraception, including one barrier method, during their participation in this study and for 6 months after stopping study treatment with olaparib and/or AZD5153. Female partners of child-bearing potential of male patients must use at least one of the two forms of acceptable contraception. * Male patients must agree to refrain from donating sperm during their participation in the study and until 6 months after the last treatment with olaparib and/or AZD5153. * Male patients will be counselled about the effects of the drug on their fertility and the utility of freezing their sperm samples prior to the start of the study should they wish to father children while on AZD5153 or during the 6 months after stopping AZD5153. 13. Female patients must use two highly effective contraceptive measures. All methods of contraception (with the exception of total abstinence) should be used in combination with the use of a condom by a male sexual partner for intercourse. Female patients must not be breast-feeding and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening: * Post-menopausal women defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatment. * Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation. Additional Inclusion Criteria Specific for Monotherapy Dose Escalation: 1. Patients with histological or cytological confirmation of a malignant solid tumor (locally advanced or metastatic) or lymphoma (any histology) that is refractory to standard therapy(ies) or for which no standard therapy(ies) exists. \- Patients with a malignant solid tumor must have at least 1 lesion that can be accurately measured at baseline by computed tomography (CT) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria (Eisenhauer et al. 2009) and is suitable for repeated measurement. 2. Patients with lymphoma must have documented analysis of bone marrow infiltration from biopsy carried out \< 3 months of enrollment, or be able to undergo a new bone marrow biopsy if such procedure was performed \> 3 months prior to enrollment. \- Patients with a lymphoma must have at least 1 lesion that can be accurately assessed at baseline by CT or CT and positron emission tomography (PET) according to the Cheson criteria (Cheson et al 2007 and is suitable for repeated assessment. 3. Patient must agree to the collection of formalin fixed paraffin-embedded (FFPE) blocks or slides from archival diagnostic histology samples, or a fresh pre-treatment biopsy will be accepted. Additional Inclusion Criteria specific for MTD monotherapy expansion and olaparib combination dose escalation: 1. Patients with the following histologies that have at least 1 lesion that can be accurately assessed at baseline by CT scan according to RECIST v1.1 criteria (Eisenhauer et al. 2009) and is suitable for repeated assessment: 1. Histologically or cytologically confirmed platinum-resistant OR platinum-refractory HGSO, fallopian, or primary peritoneal cancer in the relapsed setting. Platinum-resistant disease is defined by progression within 6 months following the last administered platinum-based regimen. Platinum-refractory disease is defined by lack of at least a partial response while on platinum-containing regimens. 2. Triple-negative breast cancer (TNBC) that is refractory to standard therapy(ies) or for which no standard therapy(ies) exists 3. Refractory metastatic castrate-resistant prostate cancer (mCPRC) 4. Pancreatic ductal adenocarcinoma (PDAC) with progression on standard treament 2. Patients will be allowed on study regardless of their BRCA mutational status. Information about their BRCA mutational status or other HRD gene mutational status must be collected if patients have been tested as part of their standard of care. 3. Previous response to olaparib or other PARPi is not required 4. Patients must have at least 1 site of disease amenable to biopsy at screening, and must be a candidate for tumor biopsy. Patients must be willing to undergo a new tumor biopsy during screening. An on-treatment tumor biopsy will be mandatory in the olaparib combination dose escalation portion of this study, and optional from consenting patients in the monotherapy expansion at MTD. 5. For the olaparib combination portion of this study, patients are required to have hemoglobin ≥10 g/dL at study entry. Exclusion Criteria: 1. Patients who have been treated with most recent chemotherapy, radiotherapy, hormonal therapy, immunotherapy or investigational drugs within 21 days or 5 half-lives (whichever is shorter) from enrollment. 2. Minimum wash-out period for previous PARPi therapy is at least 14 days or 5 half-lives whichever is shorter, or until toxicity from previous PARPi therapy has fully recovered. 3. Patient received more than 5 prior lines of treatment for an advanced solid tumor (including HGSO cancer, TNBC, mCRPC, or PDAC). Patients with lymphoma will be able to enroll without a restriction in the number of previous therapies received, if they otherwise meet eligibility criteria. 4. Major surgery (excluding placement of vascular access) ≤ 21 days from the beginning of enrollment or minor surgical procedures ≤ 7 days. No waiting is required following implantable port and catheter placement. 5. Patient is unable to swallow oral medications or has a gastrointestinal disorder (e.g., malabsorption) that would jeopardize intestinal absorption of AZD5153 and olaparib. 6. Treatment with any of the following: * Patient has had prescription or non-prescription drugs or other products known to be strong or moderate inhibitors/inducers of CYP3A4/5, or CYP3A4/5 sensitive substrates or substrates with a narrow therapeutic range, which cannot be discontinued 2 weeks prior to the first day of dosing and withheld throughout the study until 2 weeks after the last dose of AZD5153 and/or olaparib. * Drugs that are sensitive substrates of the transporters P-gp, UGT1A1, BCRP, OATP1B1, OAT3, OCT1, OCT2, MATE1 and MATE2K. * Herbal preparations/medications are not allowed throughout the study. These herbal medications include, but are not limited to: St. John's wort, kava, ephedra (ma huang), ginkgo biloba, dehydroepiandrosterone, yohimbe, saw palmetto, and ginseng. Patients should stop using these herbal medications 14 days prior to the first dose of AZD5153 and/or olaparib. * Drugs known to prolong QT interval or induce Torsades de Pointes. 7. Refractory nausea and vomiting, previous significant bowel resection that would preclude adequate absorption of study drug and chronic gastrointestinal disease including active or prior documented inflammatory bowel disease. 8. Patient has a history of tuberculosis. 9. Patients receiving a live attenuated vaccine ≤28 days before the first dose of study drug. 10. Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment. 11. A diagnosis of MDS or secondary AML (for olaparib combination dose escalation only) 12. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or other comorbidity that renders the patient unsuitable for participation in the study. Screening for chronic conditions is not required. 13. Any of the following cardiac criteria: * Mean resting corrected QT interval (QTcF) \>450 msec obtained from 3 electrocardiograms (ECGs). * Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block. * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age. 14. History of hypersensitivity to active or inactive excipients of AZD5153 and/or olaparib or drugs with a similar chemical structure or class to AZD5153 and/or olaparib. 15. Patients with non-Hodgkin lymphoma (NHL) at high risk for developing tumor lysis syndrome are not eligible for the monotherapy dose escalation part of this study. 16. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. 17. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.