PRIMROSE: A Modular Phase I/IIa, Multi-centre, Dose Escalation, and Expansion Study of AZD3470, a MTA Cooperative PRMT5 Inhibitor, as Monotherapy and in Combination With Anticancer Agents in Patients With Advanced/Metastatic Solid Tumours That Are MTAP Deficient

JRCT ID: jRCT2031230577

Registered date:18/01/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced Solid Tumours That Are MTAP Deficient
• Date of first enrollment: 14/02/2024
• Target sample size: 19
• Countries of recruitment: United States,Japan,France,Japan,Spain,Japan,Netherlands,Japan,Australia,Japan,South Korea,Japan,China,Japan
• Study type: Interventional
• Intervention(s): AZD3470

Outcome(s)

Primary Outcome

- Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From time of informed consent to 28 days post last dose of AZD3470 ]
Number of participants with AEs and SAEs

- Incidence of dose-limiting toxicities (DLT) [ Time Frame: From first dose of study treatment until the end of Cycle 1 (each cycle is 21 days) ]

Incidence of dose-limiting toxicities (DLT) as determined by number of patients with at least 1 dose-limiting toxicity (DLT). DLT is defined as an AE (adverse event) or abnormal laboratory value that occurs during the DLT evaluation period (defined as 21 days after the start of study intervention) that is assessed as unrelated to the disease, intercurrent illness, or concomitant medications and meets any DLT criteria defined in the clinical study protocol

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- 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.

- Willing to provide archival and/or baseline tumour sample to meet the minimum tissue requirement for central MTAP deficiency testing.

- Participants must have received and progressed, are refractory or are intolerant to standard therapy for the specific tumour type. All participants are required to have had at least one prior line of treatment in the recurrent or metastatic setting.

- MTAP deficient tumours defined as evidence of homozygous deletion of one or more exons of the MTAP gene in tumour tissue AND/OR loss of MTAP expression in the tumour tissue.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

- A minimum life expectance of 12 weeks in the opinion of the Investigator.

- Participants must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1

- Adequate organ and bone marrow reserve function.

- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclude criteria

- Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease.

- Allogenic organ transplantation.

- Any significant laboratory finding or any severe and uncontrolled medical condition.

- Any of the following cardiac criteria:
LVEF 50% or less
_ 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

- Use of therapeutic anti-coagulation for treatment of active 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.

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT06130553