AZD3470 for Advanced/metastatic solid tumours with MTAP deficiency

Inclusion criteria

• {"criterion_text":"- Participant must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the ICF."}
• {"criterion_text":"- Willing to provide archival and/or baseline tumor sample to meet the minimum tissue requirement for central MTAP deficiency testing."}
• {"criterion_text":"- Participants must have received and progressed, are refractory or are intolerant to standard therapy for the specific tumor type. All participants are required to have had at least one prior line of treatment in the recurrent or metastatic setting."}
• {"criterion_text":"- MTAP deficient tumors defined as evidence of homozygous deletion of one or more exons of the MTAP gene in tumor tissue AND/OR loss of MTAP expression in the tumor tissue."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1."}
• {"criterion_text":"- A minimum life expectance of 12 weeks in the opinion of the Investigator."}
• {"criterion_text":"- Participants must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1."}
• {"criterion_text":"- Adequate organ and bone marrow reserve function."}
• {"criterion_text":"- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies."}

Exclusion criteria

• {"criterion_text":"- Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease or primary malignancies of the central nervous system. - Allogeneic organ transplantation. - Any significant laboratory finding or any severe and uncontrolled medical condition - Any of the following cardiac criteria: - LVEF ≤ 50%, prior or current cardiomyopathy - clinically active cardiovascular disease, or a history of myocardial infarction within the last 6 months - uncontrolled Angina or acute coronary syndrome within 6 months - severe valvular heart disease - uncontrolled hypertension - risk of brain perfusion problems, stroke or transient ischemic attack in the last 6 months, undergone coronary artery bypass graft, angioplasty or vascular stent - chronic heart failure - factors that increase the risk of QTc prolongation or risk of arrhythmic events - Mean resting QTcF > 470 msec or any clinically important abnormalities in rhythm"}
• {"criterion_text":"- Use of therapeutic anti-coagulation for treatment of acute thromboembolic events. - Serologic active hepatitis B or C infection. - Known to have tested positive for Human immunodeficiency virus (HIV). - Confirmed or suspected ILD/pneumonitis or history of (non-infectious) ILD/pneumonitis that required oral or IV steroids or supplemental oxygen - Active gastrointestinal disease or other condition that would interfere with oral therapy. - History of another primary malignancy. - Unresolved toxicities from prior anti-cancer therapy, except alopecia and neuropathy. - Prior treatment with a protein arginine methyltransferase 5 (PRMT5) inhibitor."}

Primary endpoints

• {"endpoint_text":"- Incidence of adverse events (AEs) determined by the number of patients with adverse events by system organ class and preferred term.","definition_or_measurement_approach":"Determined by the number of patients with adverse events by system organ class and preferred term."}
• {"endpoint_text":"- Incidence of serious adverse events (SAEs) determined by the number of patients with adverse events by system organ class and preferred term.","definition_or_measurement_approach":"Determined by the number of patients with adverse events by system organ class and preferred term."}
• {"endpoint_text":"- Incidence of dose-limiting toxicities (DLT) as determined by number of patients with at least 1 dose-limiting toxicity (DLT) as defined by the clinical study protocol","definition_or_measurement_approach":"Number of patients with at least one DLT as defined by the clinical study protocol."}

Secondary endpoints

• {"endpoint_text":"- Radiological response assessed by the Investigator evaluated according to RECIST v1.1 1. Objective response rate (ORR) - The percentage or number of participants who have a confirmed investigator assessed complete or partial response as determined by the investigator according to response criteria in solid tumors (RECIST v1.1).","definition_or_measurement_approach":"Radiological response per RECIST v1.1 assessed by Investigator; ORR = confirmed complete or partial responses per RECIST v1.1."}
• {"endpoint_text":"- Duration of response (DOR) - the time from date of first documented objective response (which is subsequently confirmed) until date of documented disease progression per Tumor RECIST v1.1 as assessed by the Investigator at local site or death due to any cause.","definition_or_measurement_approach":"Time from first documented objective response (confirmed) until documented disease progression per RECIST v1.1 or death."}
• {"endpoint_text":"- Disease Control Rate (DCR) at 12 weeks- defined as the percentage of participants who have a confirmed CR or PR or who have SD per RECIST 1.1 as assessed by the Investigator at local site and derived from the raw tumor data for at least 11 weeks after date of first dose to allow for an early assessment within the assessment window.","definition_or_measurement_approach":"Percentage of participants with confirmed CR or PR or SD per RECIST 1.1 at 12 weeks as assessed by Investigator; derived from raw tumor data for ≥11 weeks after first dose."}
• {"endpoint_text":"- Best percentage change in tumor size - Percentage change from baseline in TL (target lesion) tumor-size is based on the RECIST 1.1 TL measurements as assessed by the Investigator.","definition_or_measurement_approach":"Percent change from baseline in target lesion size per RECIST 1.1 measurements by Investigator."}
• {"endpoint_text":"- Progression Free Survival (PFS) - defined as time from date of first dose (nonrandomized study parts) or date of randomization (randomized study parts) until progression per RECIST v1.1 as assessed by the Investigator at local site, or death due to any cause.","definition_or_measurement_approach":"Time from first dose (or randomization if randomized part) until progression per RECIST v1.1 by Investigator or death."}
• {"endpoint_text":"- Overall Survival (OS) - defined as time from date of first dose (nonrandomized study parts) or date of randomization (randomized study parts) until the date of death due to any cause.","definition_or_measurement_approach":"Time from first dose (or randomization) until date of death from any cause."}
• {"endpoint_text":"- Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: Area under the concentration time curve (AUC), maximum observed plasma concentration of the study drug (Cmax), Time to maximum observed plasma concentration of the study drug (T-max), Terminal elimination half-life (t 1/2), amount of AZD3470 excreted in urine (Ae), renal clearance (Clr)","definition_or_measurement_approach":"Measurement of PK parameters (AUC, Cmax, Tmax, t1/2, Ae, Clr) following dosing in dose escalation Part A."}
• {"endpoint_text":"- (USA ONLY) Module 1 Endpoints Part A (DDI) - Plasma geometric mean ratio (Cmax and AUC) of Midazolam evaluated with and without AZD3470 - Plasma geometric mean ratio (Cmax and AUC) of Dextromethorphan evaluated with and without AZD3470 - Percentage change from baseline tumor SDMA as measured by immunohistochemistry.","definition_or_measurement_approach":"DDI evaluation: plasma geometric mean ratios (Cmax and AUC) for midazolam and dextromethorphan with/without AZD3470; percent change from baseline tumor SDMA by IHC."}

France

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

01-08-2025

Processing Time Days

484

Number Of Sites

2

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

25-08-2025

Processing Time Days

508

Number Of Sites

3

Number Of Participants

15

Netherlands

Earliest CTIS Part Ii Submission Date

05-04-2024

Latest Decision Or Authorization Date

02-09-2025

Processing Time Days

515

Number Of Sites

1

Number Of Participants

10

Primary sponsor

Full Name

Astrazeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden