A Trial of Ipatasertib in Combination With Atezolizumab

This is a Phase 1 trial of atezolizumab in combination with ipatasertib. There are two parts to this study. Part A: dose escalation, and Part B: dose expansion. Part A: The investigators will investigate the combination of a fixed dose of atezolizumab (1200mg) in combination with escalating doses of ipatasertib in patients with advanced solid tumours (Cohort A1) and patients with resectable glioblastoma multiforme (GBM) (Cohort A2). Cohort A1 (advanced solid tumours): There will be an ipatasertib run-in phase of 14 days of continuous oral dosing with paired pre and post-treatment blood and tissue samples. Combinations dosing will commence on Cycle 1 Day 1 with the atezolizumab infusion. Cycle 1 will therefore be 35 days. Only patients with advanced solid tumours recruited into Cohort A1 will be included in dose escalation decisions and determination of the MTD and recommended Phase 2 dose (RP2D) for part B. Cohort A2 (potentially resectable GBMs): There will be an ipatasertib run-in phase of at least 14 days and up to 21 days followed by surgical resection of the patient's tumour (5 day window for surgery). Ipatasertib dosing will be stopped 48 hours prior to surgery and combination dosing on Cycle1Day1 (C1D1) will commence after recovery. Accrual to Cohort A2 will run in parallel Cohort A1 without formal dose escalations and patients in Cohort A2 will not be included in dose escalation decisions for Cohort A1. Recruitment to Part A is complete. Part B: Patients will be enrolled into the expansion phase (Part B) to further characterize the tolerability of the RP2D (established in Cohort A1) of the combination in specific subgroups of patients. Part B of the study will have a pre-screening component for patients with solid tumours (Cohorts B1 and B2) to allow for enrichment for these specific subgroups of patients. Part B of the study will have three cohorts: * Cohort B1: patients with solid tumours with hyperactivation of PI3K pathway as determined by pathogenic mutations identified by next generation sequencing (NGS) (eg known activating mutations in PIK3CA, AKT1, AKT2) or PTEN loss (assessed by immunohistochemistry (IHC) (n=12). * Cohort B2: patients with castrate-resistant prostate cancer with PTEN loss as assessed by IHC (n=12) * Cohort B3: patients with glioblastoma (n=12) of which at least three (n=3) patients will have potentially resectable recurrent glioblastomas. Recruitment to cohort B3 is complete. * Cohort B4: patients with melanoma post progression on immune-checkpoint inhibitors (n=12) * Cohort B5: patients with other tumour types refractory to immune checkpoint inhibitors (where immune checkpoint inhibitors are licensed, e.g. bladder cancer, head and neck SCC, NSCLC) (n=12) * Cohort B6: patients with gynaecological cancers (including ovarian cancer, cervical cancer, endometrial cancer) (n=12) Approximately 12 patients with solid tumours and 3 patients with glioblastoma will be entered into Part A of this trial and a further 72 patients will be enrolled into part B of the trial for an expected maximum of 87 patients on the study. If the MTD is reached in Part A with less than 15 patients enrolled, the investigators may enrol further patients at the R2PD in Part A to a maximum of 15 patients to include sufficient numbers of patients for the proof-of-concept translational studies. Additional subjects may be enrolled in a given cohort to ensure that the required number of evaluable subjects in each cohort is achieved.