Experimental combo targets Hard-to-Treat cancers

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Capable of giving informed consent. 2. Males and females ≥18 years of age. 3. Weight ≥ 30 kg. 4. Histologic confirmation of a solid tumour, excluding lymphoma, refractory to standard therapy or for which no standard of care regimen exists. 5. Measurable or non-measureable disease according to RECIST v1.1. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 7. Baseline laboratory values within 7 days prior to receiving study drugs (without transfusion support): * Absolute neutrophil count (ANC) ≥1500/μL * Haemoglobin (HgB) ≥9 g/dL * Platelets ≥100,000/μL * Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 x Upper Limit of Normal (ULN). * Serum bilirubin within normal limits (WNL) or ≤ 1.5 x ULN in patients with liver metastases; or total bilirubin ≤ 3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome. * Serum creatinine ≤ 1.5 x ULN, or creatinine clearance (CrCl) ≥ 40 mL/min as calculated by Cockcroft-Gault method. 8. Fertile females of child-bearing potential who agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after the last dose of AZD1775 (adavosertib) or 3 months after the last dose of MEDI4736 (durvalumab), whichever is later, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 3 days prior to the start of study treatment. 9. Male patients must agree to use at least one medically acceptable form of contraception for the duration of the study and for 3 months after the last dose of AZD1775 (adavosertib) and MEDI4736 (durvalumab), whichever is later. 10. Predicted life expectancy ≥ 12 weeks. 11. Willing to provide consent for the collection of biological samples including circulating tumour DNA (ctDNA), and blocks or slides from archival diagnostic samples, or fresh tumour biopsy (if archival is not available) for analyses. 12. Willingness and ability to comply with study and follow-up procedures. Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 2. Previous enrolment in this study. 3. Concurrent enrolment in another interventional clinical study. 4. Participation in another interventional clinical study or study with an investigational product during the last 28 days or 5 half-lives whichever is shorter. 5. Major surgical procedures (as defined by the Investigator) ≤28 days of beginning study treatment, or minor surgical procedures (as defined by the Investigator) ≤7 days. No waiting period required following Port-a-Cath placement. Note: Local surgery of isolated lesions for palliative intent is acceptable. 6. Palliative radiation therapy completed ≤ 7 days prior to start of study drugs. 7. No other anti-cancer therapy (chemotherapy, immunotherapy, hormonal anti-cancer radiotherapy \[except for palliative local radiotherapy\]), biological therapy or other novel agent is permitted while the patient is receiving study medication. Patients on luteinizing hormone-releasing hormone (LHRH) analogue treatment for more than 6 months are allowed entry into the study and can continue this treatment during the study. 8. Any unresolved NCI CTCAE Grade \>1 toxicity from prior therapy (except alopecia or anorexia). Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with AZD1775 (adavosertib) or MEDI4736 (durvalumab) may be included after consultation with the Medical Monitor. 9. Inability to swallow oral medication. 10. Brain metastases or spinal cord compression unless the patient is stable (asymptomatic, no evidence of new or emerging brain metastases) and off steroids for at least 14 days prior to start of study treatment. Following radiotherapy and/or surgery, patients with brain metastases must wait 4 weeks following the intervention and must confirm stability with imaging before enrolment. Patients with suspected brain metastases at screening should have a CT/MRI of the brain prior to study entry. Brain metastases will not be recorded as RECIST target lesions (TL) at baseline. 11. History of leptomeningeal carcinomatosis. 12. Ascites requiring intervention (e.g. need for paracentesis or Tenckhoff catheter). 13. History of primary immunodeficiency. 14. History of tuberculosis. 15. Organ transplant that requires the use of immunosuppressive treatment. 16. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g. colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematous; sarcoidosis syndrome, or Wegner syndrome; Grave's disease; rheumatoid arthritis, hypophysitis, uveitis, etc.). The following are exceptions to this criterion: vitiligo or alopecia, hypothyroidism stable on hormone replacement, chronic skin condition that does not require treatment, patients without active disease in the last 5 years may be included after consultation with Medical Monitor, patients with celiac disease controlled by diet alone. 17. Any of the following cardiac diseases currently or within the last 6 months: unstable angina pectoris, congestive heart failure, acute myocardial infarction, heart failure ≥ 2 defined by NYHA, conduction abnormality not controlled with pacemaker or medication, significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible), history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. 18. Uncontrolled hypertension. 19. Interstitial lung disease. 20. Known active cancers. 21. Mean resting corrected QT interval (specifically QTc calculated using the Fridericia formula \[QTcF\]) \> 450 msec for males and \> 470 msec for females from 3 ECGs performed within 2-5 minutes apart at study entry or congenital long QT syndrome. 22. Known serious active infection at study entry. 23. Serious chronic gastrointestinal conditions associated with diarrhoea within the past 12 months. 24. Pregnant or lactating. 25. Previous allogeneic bone marrow transplant. 26. Psychiatric illness or social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. 27. Use of approved treatment (e.g. chemotherapy, targeted therapy, biologic therapy, or monoclonal antibody \[mAb\]) ≤ 21 days prior to the first dose of study drug. If there are questions relating to this criterion, a longer wash-out period may be required after discussion with the Medical Monitor. 28. Current or prior use of WEE-1 inhibitor or any immunosuppressive medication (e.g. anti-PDL1, anti-PD1, or previous cell-depleting therapies such as alemtuzumab, anti-CD4, anti-CD5, anti-CD3, anti-CD20, etc.) ≤ 14 days prior to the first dose of MEDI4736. The following are exceptions to this criterion: Intranasal, inhaled, topical, or local steroid injections (e.g. intra-articular injection), systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent. Please note: This does not include use of corticosteroids as part of antiemetic prophylaxis or treatment in relation to AZD1775 (adavosertib) dosing or steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication). 29. Any known allergy, hypersensitivity or contraindication to the components of the study drug AZD1775 (adavosertib) or MEDI4736 (durvalumab) or any of their excipients, or to corticosteroids. 30. Prior randomisation in a previous MEDI4736 (durvalumab) clinical study regardless of treatment arm assignment. 31. Receipt of live attenuated vaccine ≤ 30 days prior to the first dose of study drug. Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP. 32. Prescription or non-prescription drugs or other products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4 which cannot be discontinued 2 weeks prior to the first day of study drug dosing and withheld throughout the study until 2 weeks after the last dose of study drug. 33. Herbal preparations must be stopped 7 days prior to first dose of study drug. 34. Any evidence of severe or uncontrolled systemic disease such as active bleeding diatheses (as judged by the Investigator), or positive for immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV). 35. Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.