LymphomaPhase 1/2PRIMAVERANCT06137144
AZD3470 as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Haematologic Malignancies.
A Phase 1/2 study testing AZD3470 and Pembrolizumab in people with Lymphoma and Non-Hodgkin Lymphoma, run by AstraZeneca at 38 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Lymphoma, Non-Hodgkin Lymphoma, Hodgkin Lymphoma
- What is being tested?
- AZD3470 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 161 participants
- Where
- 38 sitesin 11 countries
- Study dates
- 23 Jan 2024to 3 May 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Core Inclusion criteria:
- 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.
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- 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:
- 1- Participants must be at least 50 years of age or older at study entry. 2- Histologically confirmed diagnosis of cHL based on WHO criteria 3- Ann Arbor stages III or IV. 4- 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.
- 5- Participants must provide FFPE baseline tumour tissue.
- Module 1 Cohort 3:
- Participants must be aged ≥ 18 years at the time of signing the informed consent.
- Histologically confirmed diagnosis of PTCL NOS, systemic ALCL, or AITL based on WHO criteria.
- 2a- If pre-screening for MTAP deficiency is initiated, all participants must be MTAP deficient as determined by a local test.
- 3- Participants must have received at least 1 prior line of therapy for the treatment of PTCL and have exhausted all available therapies with demonstrated clinical benefit. Participants with ALCL must have received prior BV treatment.
- 4- Participants must provide FFPE baseline tumour tissue
- Ability to provide an on-treatment biopsy (if the tumour is suitable for biopsy).
- 5- At least 1 radiographically measurable, and/or FDG-avid lymphoma lesions (> 1.5 cm for nodal lesion and >1 cm for extranodal lesion).
- Module 2 Cohort 1:
- 1- Participants must be aged ≥ 18 years at the time of signing the informed consent.
- 2- Histologically confirmed diagnosis of cHL based on WHO criteria 3- At least 1 radiographically measurable, and/or FDG-avid lymphoma lesions (> 1.5 cm for nodal lesion and >1 cm for extranodal lesion).
- 4- Participant must have received at least 1 prior line of therapy for the treatment of cHL and have documented r/r active disease requiring treatment.
- 5- Participants must provide FFPE baseline tumour tissue.
Who cannot join
- Core 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.
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- 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, b) Percutaneous coronary intervention or heart valve replacement or repairment, c) Vascular stent implantation (venous stent is eligible), d) Acute coronary syndrome / myocardial infarction, e) Unstable or poorly controlled angina pectoris, f) Ventricular arrhythmias requiring continuous therapy, g) Uncontrolled atrial fibrillation, h) Haemorrhagic or thrombotic stroke (including transient ischaemic attacks) or any other CNS bleeding.
- Acute venous or atrial thromboembolic event (unless considered stable or adequately treated with at least 3months of therapeutic anticoagulation).
- Severe valvular heart disease.
- Congestive heart failure Grade II to Grade IV.
- Prior or current cardiomyopathy.
- Uncontrolled hypertension.
- History of significant haemoptysis or haemorrhage within4 weeks of the first dose of study treatment.
- Unresolved toxicities of Grade > 1 from prior anti cancer therapy (excluding peripheral neuropathy, vitiligo, alopecia and endocrine disorders that are controlled with replacement hormone therapy, and asymptomatic laboratory abnormalities), unless immune-mediated.
- History of another primary malignancy.
- Received the following anticancer therapies: anti-lymphoma therapy (within 21 days), radiation therapy(within 28 days), allo-HSCT (within 180 days), auto-HSCT/cellular therapy (within 60 days), or MAT2A or PRMT5 inhibitor
- Requires ongoing immunosuppressive therapy, including systemic corticosteroids.
- Psychiatric illness/social situations/substance abuse disorders that would limit compliance with study requirements or compromise the ability to give written informed consent.
- Use of prescription medications that are known as:
- Strong or moderate inhibitors or inducers of CYP3A4, sensitive substrates of CYP3A4, inhibitors or substrates of CYP2D6, inhibitors and sensitive substrates of CYP2C8, and NTI substrates of CYP3A4, CYP2D6, and CYP2C8.
- Received live, attenuated vaccine within 30 days prior to first dose of treatment.
- Known hypersensitivity to AZD3470 or any of the excipients of the product.
- Involvement in planning or conduct of the study (applies to both AstraZeneca staff and site staff).
- Judgement by investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.
- Previous enrolment in the present study.
- Pregnant (confirmed with positive pregnancy test) or breastfeeding or intends to become pregnant during the study.
- Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up period of an interventional study.
- Module 2 Cohort 1:
- <!-- -->
- History of confirmed ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment or any evidence of clinically active ILD or pneumonitis.
- ≥Grade 3 immune-mediated AE while receiving prior checkpoint inhibitor immunotherapy, or any unresolved ≥Grade 2 immune-mediated AE.
- History of immune-mediated myocarditis or pericarditis.
- Experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
- Active or prior documented pathologically confirmed autoimmune or inflammatory disorders
- Refractory to prior checkpoint inhibitor therapy (within 12 weeks of last dose)
- Eligible for allogeneic or autologous stem cell transplant.
- Received an allogeneic HSCT within 5 years of the first dose of study treatment; must not have active Graft-versus-host disease.
- Participants with a known hypersensitivity to pembrolizumab or any of the excipients of the product.
Trial locations and contacts
38 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
38 sites in 11 countries
United States7 sites, 6 recruiting
- Withdrawn
Research Site
Atlanta, Georgia, 30322
- Recruiting
Research Site
Boston, Massachusetts, 02215
- Recruiting
Research Site
Duarte, California, 91010
- Recruiting
Research Site
Houston, Texas, 77030
- Recruiting
Research Site
Miami, Florida, 33136
- Recruiting
Research Site
New York, New York, 10016
- Recruiting
Research Site
Philadelphia, Pennsylvania, 19104
Australia6 sites, 2 recruiting
- Withdrawn
Research Site
Adelaide, 5000
- Withdrawn
Research Site
Birtinya, 4575
- Recruiting
Research Site
Fitzroy, 3065
- Recruiting
Research Site
Nedlands, 6009
- Withdrawn
Research Site
South Brisbane, 4101
- Withdrawn
Research Site
Waratah, 2298
France5 sites, 4 recruiting
- Terminated
Research Site
Créteil, 94010
- Recruiting
Research Site
Dijon, 21079
- Recruiting
Research Site
Lille, 59000
- Recruiting
Research Site
Pierre-Bénite, 69310
- Recruiting
Research Site
Villejuif, 94805
Germany4 sites, 4 recruiting
- Not yet recruiting
Research Site
Berlin, 12203
- Recruiting
Research Site
Cologne, 50937
- Not yet recruiting
Research Site
Erlangen, 91054
- Recruiting
Research Site
Würzburg, 97080
China3 sites, 3 recruiting
- Recruiting
Research Site
Beijing, 100191
- Recruiting
Research Site
Guangzhou, 510060
- Recruiting
Research Site
Shanghai, 20032
Italy3 sites, 3 recruiting
- Recruiting
Research Site
Alessandria, 15100
- Recruiting
Research Site
Bologna, 40138
- Recruiting
Research Site
Milan, 20141
Brazil2 sites, 2 recruiting
- Not yet recruiting
Research Site
São Paulo, 01401-002
- Not yet recruiting
Research Site
São Paulo, 05652-900
Japan2 sites, 2 recruiting
- Recruiting
Research Site
Bunkyō City, 113-8677
- Recruiting
Research Site
Kōtoku, 135-8550
South Korea2 sites, 2 recruiting
- Recruiting
Research Site
Seoul, 03080
- Recruiting
Research Site
Seoul, 06351
Spain2 sites, 2 recruiting
- Recruiting
Research Site
L'Hospitalet de Llobregat, 08908
- Recruiting
Research Site
Madrid, 28041
United Kingdom2 sites, 2 recruiting
- Recruiting
Research Site
Manchester, M20 4BX
- Recruiting
Research Site
Oxford, OX3 7LE
About this study
Official title: 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
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.
Read the detailed description
This is a modular, Phase I/II, open-label, multicentre study of AZD3470 in participants with haematologic malignancies. The study consists of several study modules, each evaluating the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of orally administered AZD3470 as a monotherapy and in combination with other anticancer agent(s).
Module 1 Cohort 1 will evaluate AZD3470 monotherapy in adults and adolescents with r/r cHL who have received at least 2 prior lines of anticancer therapy. Part A (dose escalation) will assess AZD3470 at increasing doses to determine Maximum Tolerated Dose and Recommended Dose for Expansion in participants aged 18 years or older. Part B (dose optimization/expansion) will include participants to selected dose levels that were evaluated in Part A to support the recommended phase II dose (RP2D). Safety, tolerability, PK, preliminary efficacy, and food effect will be assessed. Adolescent participants (aged 12 years and older) will only be enrolled in Part B once sufficient supportive adult safety/PK data is reviewed and agreed upon with Safety Review Committee.
Module 1 Cohort 2 will evaluate AZD3470 monotherapy as a consolidation therapy in advanced stage (Stage III/IV) cHL participants aged 50 years or older, who have achieved a response (CR or PR) after at least 4 cycles of frontline standard of care therapy. Safety and tolerability, PK, Pharmacodynamics and preliminary efficacy will be evaluated.
Module 1 Cohort 3 will evaluate AZD3470 monotherapy in participants with r/r PTCL (PTCL NOS, ALCL, AITL) aged 18 years or older, who have received at least one prior anticancer therapy. Safety and tolerability, PK, Pharmacodynamics, and preliminary efficacy will be evaluated.
Module 2 Cohort 1 will evaluate AZD3470 in combination with pembrolizumab in r/r cHL participants aged 18 years or older, who have received at least one prior anticancer therapy. Part A (dose escalation) will include participants at select dose levels below or at the highest tolerable monotherapy dose in Module 1 Cohort 1.
Part B (dose optimization/expansion) will include participants to selected dose levels that were evaluated in Part A to support the recommended combination phase II dose (RP2D). Safety, tolerability, PK, Pharmacodynamics and preliminary efficacy, will be evaluated.
The protocol may be amended in the future to incorporate additional cohorts in combination with pembrolizumab or new modules evaluating AZD3470 in combination with other anticancer agents in haematologic malignancies.
- Conditions
- Lymphoma, Non-Hodgkin Lymphoma, Hodgkin Lymphoma, Peripheral T-cell Lymphoma (PTCL), PTCL-NOS, ALCL
- Being tested
- AZD3470, Pembrolizumab
- Keywords
- Haematologic Malignancies, Hodgkin lymphoma, Peripheral T-cell lymphoma (PTCL), Methylthioadenosine Phosphorylase (MTAP) deficient, Protein Arginine Methyltransferase 5 (PRMT5)
- Medical subject headings
- Lymphoma, Lymphoma, Non-Hodgkin, Hodgkin Disease, Lymphoma, T-Cell, Peripheral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD3470Drug
AZD3470 is a novel, potent and selective, second-generation, Methylthioadenosine (MTA)-selective, small molecule inhibitor of PRMT5.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab (CAS nr: 1374853-91-4
)
| Study group | Role | What they receive |
|---|---|---|
| AZD3470 Monotherapy | Experimental | Module 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. Receives: Drug: AZD3470 |
| AZD3470 in combination with Pembrolizumab | Experimental | Module 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). Receives: Drug: AZD3470; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Applicable to Module 1 Cohort 1 and 3, and Module 2 Cohort 1: ORR is defined as the proportion of participants who have a CR or PR and CRR is defined as the proportion of participants who have a CR.
Assessment of ORR/CRR will be done according to the Lugano Classification for cHL and PTCL
Measured: 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)
Applicable to Module 1 Cohort 2: PR to CR conversion rate is defined as the proportion of participants who have a PR at baseline after induction therapy, who subsequently achieve a CR. PR and CR are assessed by investigators according to Lugano classification for lymphoma.
Measured: 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)
Applicable to Module 1 Cohort 1 and Cohort 3 and Module 2 Cohort 1: For the patients who have achieved an objective response (CR or PR), the time from the date of first documented response until the date of documented progression as assessed by the investigator according to the Lugano classification for cHL and PTCL, or death due to any cause (in absence of disease progression).
Measured: 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
Applicable to Module 2 Cohort 1: Rate of durable complete response is defined as the proportion of participants who have a CR with a duration according to CSP-defined timelines.
Measured: 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)
Applicable to all cohorts: Time from date of first dose (non- randomised study parts) or date of randomization (randomised study parts) until progression as assessed by the investigator according to the Lugano Classification for cHL and PTCL, or death, due to any cause.
Measured: 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
Response Endpoints as assessed by the investigator according to the Lugano Classification: Overall Survival (OS)
Applicable to all cohorts: Time from date of first dose (non-randomised study parts) or date of randomization (randomised study parts) until the date of death due to any cause.
Measured: 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
Measurement of Plasma PK parameters: AUC, Cmax, tmax, Ctrough, t1/2 λz, CL/F, and Vz/F
Applicable to all cohorts: Assessed to characterize the plasma PK profile of AZD3470.
Measured: From Cycle 1 Day 1 (each cycle is 21 days) to EoT, at predefined intervals throughout the treatment period.
Measurement of Plasma PK parameters under fed or fasted conditions: Ratio of Cmax, Tmax, and AUCtau
Applicable to Module 1 Cohort 1 Part B: Preliminary food effect on plasma PK of AZD3470 administered as a monotherapy in participants enrolled in dose expansion.
Measured: From Cycle 1 Day 1 to Cycle 2 Day 1 at predefined intervals (each cycle is 21 days).
Urine PK parameters including Cumulative percentage of unchanged drug in urine (Ae,tau) during dosing interval and renal clearance
Applicable to Module 1 Cohort 1 Part A: Assessed to characterize the urine PK profile of AZD3470.
Measured: From Cycle 1 Day 1 to end of Cycle 1 at predefined intervals throughout the cycle (each cycle is 21 days).
Percentage change from baseline tumour SDMA mesaured by IHC.
Applicable to Module 1 Cohort 3: To asses the inhibition of PRMT5 in tumour
Measured: From Screening to EoT, at predefined intervals throughout the treatment period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2023
- Study start23 Jan 2024
- Primary completion3 May 2029 (estimated)
- Study completion3 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 161 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06137144
- Sponsor's protocol ID
- D9971C00001
- Other IDs
- 2023-506747-42-00, 2023
- Acronym
- PRIMAVERA
- Status last verified
- Oct 2026
- First submitted
- 2 Nov 2023
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06137144
- Acronym / sponsor ID
- PRIMAVERA / D9971C00001
- Conditions
- Lymphoma, Non-Hodgkin Lymphoma, Hodgkin Lymphoma, Peripheral T-cell Lymphoma (PTCL), PTCL-NOS, ALCL
- Keywords
- Haematologic Malignancies, Hodgkin lymphoma, Peripheral T-cell lymphoma (PTCL), Methylthioadenosine Phosphorylase (MTAP) deficient, Protein Arginine Methyltransferase 5 (PRMT5)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 161 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 23 Jan 2024 (actual)
- Primary completion
- 3 May 2029 (estimated)
- Study completion
- 3 May 2029 (estimated)
- First posted
- 18 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a modular, Phase I/II, open-label, multicentre study of AZD3470 in participants with haematologic malignancies. The study consists of several study modules, each evaluating the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of orally administered AZD3470 as a monotherapy and in combination with other anticancer agent(s).
Module 1 Cohort 1 will evaluate AZD3470 monotherapy in adults and adolescents with r/r cHL who have received at least 2 prior lines of anticancer therapy. Part A (dose escalation) will assess AZD3470 at increasing doses to determine Maximum Tolerated Dose and Recommended Dose for Expansion in participants aged 18 years or older. Part B (dose optimization/expansion) will include participants to selected dose levels that were evaluated in Part A to support the recommended phase II dose (RP2D). Safety, tolerability, PK, preliminary efficacy, and food effect will be assessed. Adolescent participants (aged 12 years and older) will only be enrolled in Part B once sufficient supportive adult safety/PK data is reviewed and agreed upon with Safety Review Committee.
Module 1 Cohort 2 will evaluate AZD3470 monotherapy as a consolidation therapy in advanced stage (Stage III/IV) cHL participants aged 50 years or older, who have achieved a response (CR or PR) after at least 4 cycles of frontline standard of care therapy. Safety and tolerability, PK, Pharmacodynamics and preliminary efficacy will be evaluated.
Module 1 Cohort 3 will evaluate AZD3470 monotherapy in participants with r/r PTCL (PTCL NOS, ALCL, AITL) aged 18 years or older, who have received at least one prior anticancer therapy. Safety and tolerability, PK, Pharmacodynamics, and preliminary efficacy will be evaluated.
Module 2 Cohort 1 will evaluate AZD3470 in combination with pembrolizumab in r/r cHL participants aged 18 years or older, who have received at least one prior anticancer therapy. Part A (dose escalation) will include participants at select dose levels below or at the highest tolerable monotherapy dose in Module 1 Cohort 1.
Part B (dose optimization/expansion) will include participants to selected dose levels that were evaluated in Part A to support the recommended combination phase II dose (RP2D). Safety, tolerability, PK, Pharmacodynamics and preliminary efficacy, will be evaluated.
The protocol may be amended in the future to incorporate additional cohorts in combination with pembrolizumab or new modules evaluating AZD3470 in combination with other anticancer agents in haematologic malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AZD3470 Monotherapy | Experimental | Drug: AZD3470Module 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 | Experimental | Drug: AZD3470, Drug: PembrolizumabModule 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). |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (27 listed)
- Adequate adult (ECOG) or adolescent (Karnofsy or Lanksy) Performance Score assessments
- Adequate organ and bone marrow function.
- Age:
- 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.
Key exclusion criteria (40 listed)
- <!-- -->
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD3470AZD3470 is a novel, potent and selective, second-generation, Methylthioadenosine (MTA)-selective, small molecule inhibitor of PRMT5. | Drug | AZD3470 Monotherapy, AZD3470 in combination with Pembrolizumab |
| PembrolizumabAlso: KeytrudaPembrolizumab (CAS nr: 1374853-91-4 ) | Drug | AZD3470 in combination with Pembrolizumab |
Primary outcome
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Time frame: From Screening continuously until 28 days after the last dose of study medication.
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.
Incidence of DLTs (Dose Escalation Cohorts only)
Time frame: From first dose of AZD3470 to end of Cycle 1 (each cycle is 21 days).
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.
10 secondary outcomes
Response endpoints as assessed by the investigator according to the Lugano Classification: Objective Response Rate (ORR)/Complete Response Rate (CRR)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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
Response Endpoints as assessed by the investigator according to the Lugano Classification: Overall Survival (OS)
Time frame: 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
Measurement of Plasma PK parameters: AUC, Cmax, tmax, Ctrough, t1/2 λz, CL/F, and Vz/F
Time frame: From Cycle 1 Day 1 (each cycle is 21 days) to EoT, at predefined intervals throughout the treatment period.
Measurement of Plasma PK parameters under fed or fasted conditions: Ratio of Cmax, Tmax, and AUCtau
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 1 at predefined intervals (each cycle is 21 days).
Urine PK parameters including Cumulative percentage of unchanged drug in urine (Ae,tau) during dosing interval and renal clearance
Time frame: From Cycle 1 Day 1 to end of Cycle 1 at predefined intervals throughout the cycle (each cycle is 21 days).
Percentage change from baseline tumour SDMA mesaured by IHC.
Time frame: From Screening to EoT, at predefined intervals throughout the treatment period.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
AstraZeneca Clinical Study Information Center contact
38 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD3470 and Pembrolizumab in people with Lymphoma and Non-Hodgkin Lymphoma, run by AstraZeneca at 38 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Australia, France, Germany, China and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact AstraZeneca Clinical Study Information Center (1-877-240-9479, information.center@astrazeneca.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) (time frame: From Screening continuously until 28 days after the last dose of study medication.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.