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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06137144




Registration number
NCT06137144
Ethics application status
Date submitted
2/11/2023
Date registered
18/11/2023

Titles & IDs
Public title
AZD3470 as Monotherapy and in Combination With Anticancer Agents in Participants With Relapsed/Refractory Haematologic Malignancies.
Scientific title
A Modular Phase I/II, Open-label, Multicentre Study to Evaluate the Safety, Tolerability, and Efficacy of AZD3470, a PRMT5 Inhibitor, as Monotherapy and in Combination With Anticancer Agent(s) in Participants With Relapsed/Refractory Haematologic Malignancies
Secondary ID [1] 0 0
D9971C00001
Universal Trial Number (UTN)
Trial acronym
PRIMAVERA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma 0 0
Non-Hodgkin 0 0
Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD3470

Experimental: Module 1: Part A (Dose Escalation) and Part B (Dose Expansion/Optimization) - In Part A, participants with Relapsed/Refractory classical Hodgkin Lymphoma (cHL) will take AZD3470 tablets orally until PD, unacceptable toxicity, or withdrawal of consent.

In Part B, adult and adolescent participants with r/r cHL will take AZD3470 tablets orally until PD, unacceptable toxicity, or withdrawal of consent.


Treatment: Drugs: AZD3470
AZD3470 is a novel, potent and selective, secondgeneration, Methylthioadenosine (MTA)-selective, small molecule inhibitor of PRMT5.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Timepoint [1] 0 0
From Screening until 28 days after the last dose of study medication.
Primary outcome [2] 0 0
Incidence of DLTs (Dose Escalation only)
Timepoint [2] 0 0
From first dose of AZD3470 to end of Cycle 1 (each cycle is 21 days).
Secondary outcome [1] 0 0
Part A and Part B: Response endpoints - Objective Response Rate (ORR)/Complete Response Rate (CRR)
Timepoint [1] 0 0
From first dose (Cycle 1 Day 1, each cycle is 21 days) until disease progression or the last evaluable assessment in the absence of progression (assessed approximately up to 2 years)
Secondary outcome [2] 0 0
Part A and Part B: Response endpoints - Duration of Response (DoR)
Timepoint [2] 0 0
From first dose (Cycle 1 Day 1, each cycle is 21 days) until disease progression or death, whichever comes first (assessed approximately up to 2 years).
Secondary outcome [3] 0 0
Part A and Part B: Progression-free Survival (PFS)
Timepoint [3] 0 0
Non-randomized study parts: from first dose (each cycle is 21 days) until disease progression or death, whichever comes first. Randomized parts: from date of randomization until disease progression or death, whichever comes first. (Approx up to 2 years)
Secondary outcome [4] 0 0
Part A and Part B: Overall Survival (OS)
Timepoint [4] 0 0
Non-randomized study parts: From first dose (Cycle 1 Day 1, each cycle is 21 days) until death. Randomized study parts: from date of randomization until the date of death due to any cause (assessed approximately up to 2 years).
Secondary outcome [5] 0 0
Part A and Part B: Maximum observed plasma drug concentration (Cmax)
Timepoint [5] 0 0
From Cycle 1 Day 1 (each cycle is 21 days) to EoT, at predefined intervals throughout the treatment period (for each patient this is expected to be approximately 6 months).
Secondary outcome [6] 0 0
Part A: Dose normalised maximum observed plasma drug concentration (Cmax)
Timepoint [6] 0 0
From Cycle 1 Day 1 (each cycle is 21 days) to EoT, at predefined intervals throughout the treatment period (for each patient this is expected to be approximately 6 months).
Secondary outcome [7] 0 0
Part A: Accumulation ratio for maximum observed plasma drug concentration (Cmax)
Timepoint [7] 0 0
From Cycle 1 Day 1 (each cycle is 21 days) to EoT, at predefined intervals throughout the treatment period (for each patient this is expected to be approximately 6 months).
Secondary outcome [8] 0 0
Part A and Part B: Minimum observed plasma drug concentration (Cmin)
Timepoint [8] 0 0
From Cycle 1 Day 1 (each cycle is 21 days) to EoT, at predefined intervals throughout the treatment period (for each patient this is expected to be approximately 6 months).
Secondary outcome [9] 0 0
Part A and Part B: Time to reach peak or maximum observed concentration following drug administration (Tmax)
Timepoint [9] 0 0
From Cycle 1 Day 1 (each cycle is 21 days) to EoT, at predefined intervals throughout the treatment period (for each patient this is expected to be approximately 6 months).
Secondary outcome [10] 0 0
Part A and Part B: Area under the plasma concentration-curve over the dosing interval (AUCtau)
Timepoint [10] 0 0
From Cycle 1 Day 1 (each cycle is 21 days) to EoT, at predefined intervals throughout the treatment period (for each patient this is expected to be approximately 6 months).
Secondary outcome [11] 0 0
Part A: Dose normalized area under the plasma concentration-curve over the dosing interval (AUCtau)
Timepoint [11] 0 0
From Cycle 1 Day 1 (each cycle is 21 days) to EoT, at predefined intervals throughout the treatment period (for each patient this is expected to be approximately 6 months).
Secondary outcome [12] 0 0
Part A: Accumulation ratio for area under the plasma concentration-curve over the dosing interval (AUCtau)
Timepoint [12] 0 0
From Cycle 1 Day 1 (each cycle is 21 days) to EoT, at predefined intervals throughout the treatment period (for each patient this is expected to be approximately 6 months).
Secondary outcome [13] 0 0
Part A: Cumulative amount (%) of drug recovered unchanged in urine during dosing interval (Ae,tau)
Timepoint [13] 0 0
From Cycle 1 Day 1 to end of Cycle 1 at predefined intervals throughout the cycle (each cycle is 21 days).
Secondary outcome [14] 0 0
Part A: Renal clearance (Clr)
Timepoint [14] 0 0
From Cycle 1 Day 1 to end of Cycle 1 at predefined intervals throughout the cycle (each cycle is 21 days).
Secondary outcome [15] 0 0
Part B: Ratio of maximum observed plasma drug concentration (Cmax) under fed/fasted state
Timepoint [15] 0 0
From Cycle 1 Day 1 to Cycle 2 Day 1 at predefined intervals (each cycle is 21 days).
Secondary outcome [16] 0 0
Part B: Time to reach peak or maximum observed concentration following drug administration (Tmax) under fed conditions
Timepoint [16] 0 0
From Cycle 1 Day 1 to Cycle 2 Day 1 at predefined intervals (each cycle is 21 days).
Secondary outcome [17] 0 0
Part B: Time to reach peak or maximum observed concentration following drug administration (Tmax) under fasted conditions
Timepoint [17] 0 0
From Cycle 1 Day 1 to Cycle 2 Day 1 at predefined intervals (each cycle is 21 days).
Secondary outcome [18] 0 0
Part B: Ratio of area under the plasma concentration-curve over the dosing interval (AUCtau) under fed/fasted state
Timepoint [18] 0 0
From Cycle 1 Day 1 to Cycle 2 Day 1 at predefined intervals (each cycle is 21 days).

Eligibility
Key inclusion criteria
Inclusion criteria

* In Part A (dose escalation), participants must be aged = 18 years at the time of signing the informed consent. In Part B (dose optimization/expansion), participants must be at least 15 years of age.
* Histologically confirmed documented diagnosis of r/r cHL based on criteria established by the World Health Organization
* Willing to provide FFPE baseline tumour tissue to meet the minimum tissue requirement for central MTAP expression determination.
* Participants must have documented r/r active disease, must have previously received at least 3 prior lines of therapy for the treatment of cHL, and must have exhausted all available therapies with demonstrated clinical benefit.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Module 1 (cHL):

* At least 1 radiographically measurable, and/or FDG-avid lymphoma lesion > 1.5 cm.
* Adequate organ and bone marrow function
* Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Minimum age
15 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

* Any significant laboratory finding or any severe and uncontrolled medical condition.
* Active CNS involvement by lymphoma, leptomeningeal disease, or spinal cord compression.
* Serologic active HBV or HCV infection.
* Known to have tested positive for HIV.
* Active gastrointestinal disease or other condition that will interfere with oral therapy.
* Any of the following cardiac criteria:

* Mean resting QTcF > 470 msec or clinically important abnormalities in rhythm (ventricular arrhythmias and uncontrolled atrial fibrillation)
* Factors that increase the risk of QTc prolongation or risk of arrhythmic events
* Cardiac procedures or conditions within the last 6 months: Coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) or heart valve intervention vascular stent implantation, acute coronary syndrome / myocardial infarction, uncontrolled angina pectoris, use of therapeutic anti-coagulation for treatment of active thromboembolic events.
* Severe valvular heart disease
* Congestive heart failure Grade II to Grade IV
* Prior or current cardiomyopathy
* Uncontrolled hypertension
* Brain perfusion problems such as haemorrhagic or thrombotic stroke (including transient ischemic attacks)
* Unresolved non-haematological toxicity from prior anticancer therapy of Grade > 1, except alopecia.
* History of another primary malignancy.
* History of significant haemoptysis or haemorrhage within 4 weeks of the first dose of study treatment.
* Requires ongoing immunosuppressive therapy, including systemic corticosteroids.
* Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
8/05/2026
Actual
Sample size
Target
110
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
France
State/province [5] 0 0
Creteil
Country [6] 0 0
France
State/province [6] 0 0
Lille
Country [7] 0 0
France
State/province [7] 0 0
Pierre Benite
Country [8] 0 0
Germany
State/province [8] 0 0
Köln
Country [9] 0 0
Italy
State/province [9] 0 0
Alessandria
Country [10] 0 0
Italy
State/province [10] 0 0
Bologna
Country [11] 0 0
Italy
State/province [11] 0 0
Milan
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Seoul
Country [13] 0 0
Spain
State/province [13] 0 0
L'Hospitalet de Llobregat
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Manchester
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patientlevel data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06137144