NCT03772561: MEDIPAC

Phase I Study of AZD5363 + Olaparib + Durvalumab in Patients With Advanced or Metastatic Solid Tumor Malignancies

Recruiting now Phase 1 Last updated 22 July 2025

What this trial tests

Phase 1 trial testing AZD5363+Olaparib+Durvalumab in Solid Tumor, Adult in 40 participants. Currently enrolling.

Timeline

3 December 2018

Primary endpoint
31 December 2026

31 December 2026

Quick facts

Lead sponsor	National University Hospital, Singapore
Phase	Phase 1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	40
Start date	3 December 2018
Primary completion	31 December 2026
Estimated completion	31 December 2026
Sites	1 location across Singapore

Drugs / interventions tested

• AZD5363+Olaparib+Durvalumab — full drug profile →

Conditions studied

• Solid Tumor, Adult — all drugs for Solid Tumor, Adult →

Sponsor

National University Hospital, Singapore

Who can join

Adults 21 to 99, any sex, with Solid Tumor, Adult. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This is a Phase 1 dose-escalation study to evaluate the safety and tolerability of combination treatment of AZD5363 + Olaparib + Durvalumab and to determine the RP2D in patients with advanced or metastatic solid tumor malignancies.

The purpose of this trial is to determine if combination treatment of drugs, Olaparib, AZD5363 and Durvalumab has beneficial effects in advanced or metastatic cancers and to determine the effects it has on patients and their cancer.

Primary Objectives

• To evaluate the safety and tolerability of combination treatment AZD5363 + Olaparib + Durvalumab and determine the Maximum Tolerated Dose (MTD), Dose-Limiting Toxicities (DLTs), and Recommended Phase 2 Dose (RP2D) for patients with advanced or metastatic solid tumor malignancies.

Secondary Objectives

* To determine the pharmacodynamics (PDn) of combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies
* To describe anti-tumor response using immune RECIST of combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies

Exploratory Objectives

* To evaluate anti-tumour response using RECIST v1.1 for combination treatment AZD5363 + Olaparib + Durvalumab in patients with advanced or metastatic solid tumor malignancies
* To explore molecular correlates of the relationship between mutations in Akt/ PIK3CA/PTEN pathway and response to AZD5363 +Olaparib+ Durvalumab
* To understand the role of tumour microenvironment in regulation of intratumoral immune regulators (i.e. T-regulatory cells) in improving response to Durvalumab
* To understand the role of AZD5363 as an immunomodulator
* To evaluate the role of PD-1 and PDL-1 immunohistochemical and tumour MMR status in predicting response to immune check point inhibitors.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Combined PARP Inhibition and Immune Checkpoint Therapy in Solid Tumors.
   Peyraud F, Italiano A. · · 2020 · cited 163× · PMID 32526888 · DOI 10.3390/cancers12061502
2. Emerging role of PTEN loss in evasion of the immune response to tumours.
   Vidotto T, Melo CM, Castelli E, Koti M, et al · · 2020 · cited 163× · PMID 32327707 · DOI 10.1038/s41416-020-0834-6
3. AKT Inhibitors: New Weapons in the Fight Against Breast Cancer?
   Martorana F, Motta G, Pavone G, Motta L, et al · · 2021 · cited 154× · PMID 33995085 · DOI 10.3389/fphar.2021.662232
4. Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy.
   Giannone G, Ghisoni E, Genta S, Scotto G, et al · · 2020 · cited 119× · PMID 32575899 · DOI 10.3390/ijms21124414
5. PARP inhibitors: enhancing efficacy through rational combinations.
   Bhamidipati D, Haro-Silerio JI, Yap TA, Ngoi N. · · 2023 · cited 118× · PMID 37430137 · DOI 10.1038/s41416-023-02326-7
6. Prospects for combining immune checkpoint blockade with PARP inhibition.
   Li A, Yi M, Qin S, Chu Q, et al · · 2019 · cited 100× · PMID 31521196 · DOI 10.1186/s13045-019-0784-8
7. Resistance to immune checkpoint inhibitors in non-small cell lung cancer: biomarkers and therapeutic strategies.
   Walsh RJ, Soo RA. · · 2020 · cited 77× · PMID 32670423 · DOI 10.1177/1758835920937902
8. Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy.
   Sirico M, D'Angelo A, Gianni C, Casadei C, et al · · 2023 · cited 76× · PMID 36765661 · DOI 10.3390/cancers15030703