Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Stomach Neoplasms

Prostatic Neoplasms

Lung Neoplasms

Small Cell Lung Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Neoplasms

Urinary Bladder Neoplasms

Uterine Cervical Neoplasms

Carcinoma

Endometrial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Gonadal Disorders

Uterine Neoplasms

Uterine Diseases

Stomach Cancer

Small Cell Lung Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Pancreatic Cancer

Biliary Tract Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Paclitaxel

Carboplatin

Trastuzumab

Trastuzumab deruxtecan

Albumin-Bound Paclitaxel

Immunoglobulins

Poly(ADP-ribose) Polymerase Inhibitors

Tubulin Modulators

Antimitotic Agents

AZD5305 + Carboplatin with or without Paclitaxel

AZD5305

T- Dxd

Dato-DXd

Camizestrant

AstraZeneca Clinical Study Information Center

AZ Breast Cancer Study Navigators

Timothy Yap

This research is designed to determine if experimental treatment with PARP inhibitor, AZD5305, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced solid tumors.

This study is a Phase I/IIa modular, open-label, multi-center study of AZD5305 administered orally, either as monotherapy or in combination with other anti-cancer agents in patients with advanced solid malignancies.

The study consists of individual modules each evaluating the safety and tolerability of AZD5305 dosed as monotherapy, or with a specific combination partner:

* Module 1 (AZD5305 monotherapy)
* Module 2 (AZD5305 in combination with paclitaxel)
* Module 3 (AZD5305 in combination with carboplatin, with or without paclitaxel)
* Module 4 (AZD5305 in combination with T DXd)
* Module 5 (AZD5305 in combination with Dato-DXd).
* Module 6 (AZD5305 in combination with Camizestrant)

Modules 1 and 4 has 2 study parts: Part A consisting of dose-escalation cohorts and Part B, consisting of expansion cohorts. Modules 2, 3, 5 and 6 have only PART A.

Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies

A Modular Phase I/IIa, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies

Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal ECG parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline

A DLT is defined as any toxicity that occurs from the first dose of study treatment (either AZD5305 or combination anti-cancer agent) up to and including the planned end of Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation. DLTs occurring outside the DLT window (ie, late onset toxicities) may be defined as a DLT after consultation with the sponsor and investigators, based on the emerging safety profile.

Change in target lesion size from baseline, as defined by RECIST 1.1.

Best response until progression, as defined by RECIST 1.1.

Time from first response to progression or death , as defined by RECIST 1.1.

Time from C1D1 to progression or death, as defined by RECIST 1.1.

Time from C1D1 to complete or partial response, as defined by RECIST 1.1.

at least a 50% reduction in CA125 levels from a pre-treatment sample as defined by GCIG criteria.

The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.

The concentration of AZD5305 in plasma will be determined (Cmax will be derived).

The concentration of AZD5305 in plasma will be determined (Tmax will be derived).

Best response until progression, as defined by RECIST 1.1 or PCWG3 (bone)

Time from C1D1 to progression or death, as defined by RECIST 1.1 and PCWG3(bone).

PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment

Effect on High fat meal on PK parameters of AZD5305.PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without food

To investigate the presence of ADAs for T-DXd

Time from C1D1 to progression or death, as defined by RECIST v 1.1 summarised at the 6 month landmark (PFS6)

objective response rate and radiographic progression-free survival using RECIST v1.1.

Proportion of patients achieving a ≥ 50% decrease in PSA from baseline to the post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later (PSA50 response).

Plasma concentrations and PK parameters of AZD5305 and camizestrant after single dose and multiple dose administration, including, but not limited to:

AUC, Cmax, Tmax, as data allow

PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without camizestrant.

PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without AZD5305.

Spots Global Cancer Trial Database for additional indications below for module 4 and 5