Informations générales (source: ClinicalTrials.gov)
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
Interventional
Phase 1/Phase 2
AstraZeneca (Voir sur ClinicalTrials)
janvier 2024
mai 2029
15 septembre 2026
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Vincent RIBRAG | 17/06/2026 15:35:05 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Research Site - 59000 - Lille - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Core Inclusion criteria:
1. Adequate adult (ECOG) or adolescent (Karnofsy or Lanksy) Performance Score
assessments
2. Adequate organ and bone marrow function.
Module 1 Cohort 1:
1. Age:
1. Part A (dose escalation): aged ≥ 18 years at the time of signing the informed
consent.
2. Part B (optimization): aged ≥ 12 years of age. Adolescent participants must
weigh ≥ 40 kg.
2. Histologically confirmed diagnosis of cHL based on WHO criteria
3. 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.
4. Participants must provide FFPE baseline tumour tissue.
5. 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:
1. Participants must be aged ≥ 18 years at the time of signing the informed consent.
2. 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
1. 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.
Exclusion Criteria:
Core Exclusion criteria:
1. Any significant laboratory finding or any severe and uncontrolled medical
condition.
2. Active CNS involvement by lymphoma, leptomeningeal disease, or spinal cord
compression.
3. Serologic active HBV or HCV infection.
4. Known to have tested positive for HIV.
5. Active gastrointestinal disease or other condition that will interfere with
oral therapy.
6. 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.
7. Undergone any of the following procedures within 6 months prior to first dose:
a) 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.
i) Acute venous or atrial thromboembolic event (unless considered stable or
adequately treated with at least 3months of therapeutic anticoagulation).
8. Severe valvular heart disease.
9. Congestive heart failure Grade II to Grade IV.
10. Prior or current cardiomyopathy.
11. Uncontrolled hypertension.
12. History of significant haemoptysis or haemorrhage within4 weeks of the first
dose of study treatment.
13. 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.
14. History of another primary malignancy.
15. 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
16. Requires ongoing immunosuppressive therapy, including systemic corticosteroids.
17. Psychiatric illness/social situations/substance abuse disorders that would
limit compliance with study requirements or compromise the ability to give
written informed consent.
18. Use of prescription medications that are known as:
1. 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.
19. Received live, attenuated vaccine within 30 days prior to first dose of
treatment.
20. Known hypersensitivity to AZD3470 or any of the excipients of the product.
21. Involvement in planning or conduct of the study (applies to both AstraZeneca
staff and site staff).
22. Judgement by investigator that the participant is unlikely to comply with study
procedures, restrictions, and requirements.
23. Previous enrolment in the present study.
24. Pregnant (confirmed with positive pregnancy test) or breastfeeding or intends
to become pregnant during the study.
25. 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:
1. History of confirmed ILD, drug-induced ILD, radiation pneumonitis requiring
steroid treatment or any evidence of clinically active ILD or pneumonitis.
2. ≥Grade 3 immune-mediated AE while receiving prior checkpoint inhibitor
immunotherapy, or any unresolved ≥Grade 2 immune-mediated AE.
3. History of immune-mediated myocarditis or pericarditis.
4. Experienced a toxicity that led to permanent discontinuation of prior
immunotherapy.
5. Active or prior documented pathologically confirmed autoimmune or inflammatory
disorders
6. Refractory to prior checkpoint inhibitor therapy (within 12 weeks of last dose)
7. Eligible for allogeneic or autologous stem cell transplant.
8. Received an allogeneic HSCT within 5 years of the first dose of study
treatment; must not have active Graft-versus-host disease.
9. Participants with a known hypersensitivity to pembrolizumab or any of the
excipients of the product.