Safety, Tolerability and Pharmacokinetics of AZD1775 (Adavosertib) Plus MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumours

Completed · Phase 1

Conditions studied: Advanced Solid Tumours

In brief

This study will assess the safety, tolerability, and pharmacokinetics of AZD1775 (adavosertib) given orally in combination with intravenous MEDI4736 (durvalumab). Secondly, the immunogenicity, pharmacodynamics, and preliminary anti-tumour activity will be determined in patients with refractory solid tumours.

Key facts

Study ID

NCT02617277

Run by

AstraZeneca

People needed

56

Starts

2015-12-28

Expected to finish

2026-02-17

Last updated by the study team

2026-03-04

Who can join

Age: 18 and older, up to 130. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Capable of giving informed consent.
• Males and females ≥18 years of age.
• Weight ≥ 30 kg.
• Histologic confirmation of a solid tumour, excluding lymphoma, refractory to standard therapy or for which no standard of care regimen exists.
• Measurable or non-measureable disease according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• 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.
• 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.
• 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.
• Predicted life expectancy ≥ 12 weeks.
• 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.
• Willingness and ability to comply with study and follow-up procedures.

You may not qualify if…

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Previous enrolment in this study.
• Concurrent enrolment in another interventional clinical study.
• Participation in another interventional clinical study or study with an investigational product during the last 28 days or 5 half-lives whichever is shorter.
• 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.
• Palliative radiation therapy completed ≤ 7 days prior to start of study drugs.
• 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.
• 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.
• Inability to swallow oral medication.
• 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.
• History of leptomeningeal carcinomatosis.
• Ascites requiring intervention (e.g. need for paracentesis or Tenckhoff catheter).
• History of primary immunodeficiency.
• History of tuberculosis.
• Organ transplant that requires the use of immunosuppressive treatment.
• 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.
• 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.
• Uncontrolled hypertension.
• Interstitial lung disease.
• Known active cancers.
• 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.
• Known serious active infection at study entry.
• Serious chronic gastrointestinal conditions associated with diarrhoea within the past 12 months.
• Pregnant or lactating.
• Previous allogeneic bone marrow transplant.

Where it is running

• Research Site — Denver, Colorado, United States
• Research Site — Sarasota, Florida, United States
• Research Site — Nashville, Tennessee, United States

Full record on ClinicalTrials.gov

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