This is an open-label, fixed-sequence study to evaluate the effect of capivasertib on the pharmacokinetics (PK) of midazolam, a sensitive CYP3A substrate. The PK of midazolam will be assessed when administered alone and in combination with repeated doses of capivasertib.

This is 2 part study: Part A and Part B. Part A of the study consists of a screening period and 3 treatment periods (midazolam alone, capivasertib alone, and midazolam + capivasertib). During Part A, the PK profile of midazolam will be determined with and without capivasertib.All participants will receive capivasertib treatment (4 days on/3 days off); however, at the Investigator's discretion, ER positive breast cancer patients may also receive fulvestrant in addition to capivasertib and midazolam. Participants completing Part A without disease progression or unacceptable toxicity, who are considered likely to continue to benefit from further capivasertib treatment (with or without certain standard of care treatment) in the opinion of the Investigator will enter Part B. Part B of the study consists of an extended treatment period with capivasertib, with or without certain standard of care treatment, followed by a 30-day safety follow-up.

Part A of the study may be extended to allow the administration of midazolam on a rescheduled Cycle 1 Day 8(C1D8) and Cycle 1 Day 12(C1D12 ) visit.

Inclusion Criteria:

1. Participants with documented evidence of locally advanced inoperable or metastatic solid tumours who may be suitable to receive capivasertib treatment.
2. Eastern Cooperative Oncology Group/World Health Organization performance status 0 to 1 and with minimum life expectancy for 12 weeks.
3. Participant should have at least one lesion that can be assessed by computed tomography/magnetic resonance imaging or plain X-ray at baseline.
4. Body mass index within the range 18 to 32 kg/m^2

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. Radiotherapy with a wide field of radiation within 4 weeks of the first dose of capivasertib and/or radiotherapy with a limited field of radiation for palliation within 2 weeks prior to study intervention initiation.
2. Participants with diabetes mellitus type I or participants with diabetes mellitus type II requiring insulin treatment.
3. Undergone a major surgery within 4 weeks of the first dose of capivasertib.
4. Any unresolved toxicities from prior therapies higher than CTCAE grade 2 or any unresolved toxicity that may interfere with PK assessment at the time of study intervention initiation.
5. Participants with spinal cord compression or brain metastases.
6. Participants with severe or uncontrolled systemic diseases, active bleeding diatheses, or active infection.
7. Previous allogeneic bone marrow transplant or solid organ transplant.
8. Known immunodeficiency syndrome.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.