AZD3470 as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Haematologic Malignancies.
PRIMAVERA
A Modular Phase I/II, Open-label, Multicentre Study to Evaluate the Safety, Tolerability, and Efficacy of AZD3470, a PRMT5 Inhibitor, as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Haematologic Malignancies
2 other identifiers
interventional
161
10 countries
33
Brief Summary
This study is designed to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy following oral administration of AZD3470 as a monotherapy, and in combination with other anticancer agents in participants with haematologic malignancies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 lymphoma
Started Jan 2024
Typical duration for phase_1 lymphoma
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 2, 2023
CompletedFirst Posted
Study publicly available on registry
November 18, 2023
CompletedStudy Start
First participant enrolled
January 23, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2029
April 21, 2026
April 1, 2026
5.3 years
November 2, 2023
April 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
AEs: Number of patients with adverse events by system organ class and preferred term. SAEs: Number of patients with serious adverse events by system organ class and preferred term.
From Screening continuously until 28 days after the last dose of study medication.
Incidence of DLTs (Dose Escalation Cohorts only)
In the Dose Escalation cohorts in Part A, the number of participants with at least 1 dose-limiting toxicity (DLT), which is any toxicity defined as a DLT in the Clinical Study Protocol.
From first dose of AZD3470 to end of Cycle 1 (each cycle is 21 days).
Secondary Outcomes (10)
Response endpoints as assessed by the investigator according to the Lugano Classification: Objective Response Rate (ORR)/Complete Response Rate (CRR)
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.
Response Endpoints as assessed by investigator according to the Lugano Classification: Conversation rate of Partial Response (PR) to Complete Response (CR)
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.
Response endpoints as assessed by the investigator according to the Lugano Classification: Duration of Response (DoR)
From date of first objective response until documented progression or death due to any cause or censoring (if progression or death have not occurred)
Response endpoints as assessed by the investigator according to the Lugano Classification for CHL: The rate of durable CR
From date of first complete response until documented progression or death due to any cause or censoring (if progression or death have not occurred)
Response Endpoints as assessed by the investigator according to the Lugano Classification: Progression-free Survival (PFS)
From first dose (each cycle is 21 days)/from randomisation (for non-randomized & randomized study parts respectively) until disease progression or death, or censoring (if progression or death have not occurred) whichever is first
- +5 more secondary outcomes
Study Arms (2)
AZD3470 Monotherapy
EXPERIMENTALModule 1 Cohort 1 evaluates safety, tolerability, efficacy of AZD3470 in r/r cHL participants with 2 prior lines of systemic anticancer therapy (including BV and anti-PD1). Participants will be treated according to protocol-defined windows. Part A (dose escalation) assesses AZD3470 at increasing doses in participants aged ≥18 years, r/r cHL. Part B (dose optimization/ expansion) includes participants at certain dose levels evaluated as tolerable in Part A and may include adolescent patients aged ≥12 years, upon SRC agreement. Module 1 Cohort 2 evaluates the safety, tolerability, efficacy of AZD3470 as consolidation for Stage III/IV cHL participants aged ≥50 years after CR or PR to frontline SOC therapy (either N-AVD, A-AVD, AVD, ABVD) Module 1 Cohort 3 evaluates the safety, tolerability, preliminary efficacy of AZD3470 in participants aged ≥18 years with r/r PTCL (PTCL NOS, ALCL, AITL subtypes) with at least 1 prior line of systemic anticancer therapy.
AZD3470 in combination with Pembrolizumab
EXPERIMENTALModule 2 Cohort 1 will assess participants aged ≥18 years with r/r cHL who have received at least one prior line of anticancer therapy. Participants will receive treatment according to the protocol-defined limit, or until disease progression, unacceptable toxicity as judged by the investigator or until meeting any other discontinuation criteria, as defined in the clinical study protocol, whichever occurs first. Part A (dose escalation) will evaluate the safety and tolerability of AZD3470 in combination with Pembrolizumab. Part B (dose optimization/expansion) will evaluate dose optimization/expansion in certain dose levels of AZD3470 in combination with Pembrolizumab, based on cumulative data from dose escalation part (Part A).
Interventions
AZD3470 is a novel, potent and selective, second-generation, Methylthioadenosine (MTA)-selective, small molecule inhibitor of PRMT5.
Pembrolizumab (CAS nr: 1374853-91-4 )
Eligibility Criteria
You may qualify if:
- Adequate adult (ECOG) or adolescent (Karnofsy or Lanksy) Performance Score assessments
- Adequate organ and bone marrow function.
- Module 1 Cohort 1:
- Age:
- Part A (dose escalation): aged ≥ 18 years at the time of signing the informed consent.
- Part B (optimization): aged ≥ 12 years of age. Adolescent participants must weigh ≥ 40 kg.
- Histologically confirmed diagnosis of cHL based on WHO criteria
- Previous treatment with at least 2 prior lines of therapy for the treatment of cHL (including at least 2 cycles of BV and anti-PD1) and have documented r/r active disease requiring treatment.
- Participants must provide FFPE baseline tumour tissue.
- At least 1 radiographically measurable, and/or FDG-avid lymphoma lesion ( \>1.5 cm for nodal lesion and \>1 cm for extranodal lesion).
- Module 1 Cohort 2:
- Participants must be at least 50 years of age or older at study entry.
- Histologically confirmed diagnosis of cHL based on WHO criteria
- Ann Arbor stages III or IV.
- Participant must have previously received at least 4 cycles of SoC combination therapy with A-AVD, N-AVD, AVD, or ABVD (based on regional SOC, per investigator) as finite first-line induction therapy, and achieved at least a PR post-induction therapy.
- +14 more criteria
You may not qualify if:
- 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 ECG cardiac criteria: Mean resting QTcF \> 470 msec, clinically important abnormalities in rhythm, conduction or morphology, and/or any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
- Undergone any of the following procedures within 6 months prior to first dose:
- Coronary artery bypass graft,
- Percutaneous coronary intervention or heart valve replacement or repairment,
- Vascular stent implantation (venous stent is eligible),
- Acute coronary syndrome / myocardial infarction,
- Unstable or poorly controlled angina pectoris,
- Ventricular arrhythmias requiring continuous therapy,
- Uncontrolled atrial fibrillation,
- Haemorrhagic or thrombotic stroke (including transient ischaemic attacks) or any other CNS bleeding.
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (33)
Research Site
Duarte, California, 91010, United States
Research Site
Miami, Florida, 33136, United States
Research Site
Atlanta, Georgia, 30322, United States
Research Site
Boston, Massachusetts, 02215, United States
Research Site
New York, New York, 10016, United States
Research Site
Philadelphia, Pennsylvania, 19104, United States
Research Site
Houston, Texas, 77030, United States
Research Site
Adelaide, 5000, Australia
Research Site
Fitzroy, 3065, Australia
Research Site
Nedlands, 6009, Australia
Research Site
South Brisbane, 4101, Australia
Research Site
Waratah, 2298, Australia
Research Site
Beijing, 100191, China
Research Site
Guangzhou, 510060, China
Research Site
Shanghai, 20032, China
Research Site
Créteil, 94010, France
Research Site
Lille, 59000, France
Research Site
Pierre-Bénite, 69310, France
Research Site
Villejuif, 94805, France
Research Site
Berlin, 12203, Germany
Research Site
Cologne, 50937, Germany
Research Site
Erlangen, 91054, Germany
Research Site
Würzburg, 97080, Germany
Research Site
Alessandria, 15100, Italy
Research Site
Bologna, 40138, Italy
Research Site
Milan, 20141, Italy
Research Site
Kōtoku, 135-8550, Japan
Research Site
Seoul, 03080, South Korea
Research Site
Seoul, 06351, South Korea
Research Site
L'Hospitalet de Llobregat, 08908, Spain
Research Site
Madrid, 28041, Spain
Research Site
Manchester, M20 4BX, United Kingdom
Research Site
Oxford, OX3 7LE, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 2, 2023
First Posted
November 18, 2023
Study Start
January 23, 2024
Primary Completion (Estimated)
April 30, 2029
Study Completion (Estimated)
April 30, 2029
Last Updated
April 21, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- 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.
- Access Criteria
- 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.
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.