Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AZD3470 · 2 trials · 8 indications
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.
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.
Number of participants with AEs and SAEs.
Incidence of dose-limiting toxicities (DLT) as determined by number of patients with at least 1 dose-limiting toxicity (DLT)
PFS - defined as time from date of randomization until progression per RECIST v1.1 as assessed by the Investigator at local site, or death due to any cause.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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). |
| Module 1: AZD3470 Monotherapy | EXPERIMENTAL | Part A dose escalation and back-fill cohorts and Part B dose optimization and expansion cohorts of varying doses of AZD3470 |
| Module 2: AZD3470 in combination with Dato-DXd | EXPERIMENTAL | Varying doses of AZD3470 in combination with Dato-Dxd |
| Module 2: Dato-DXd alone | EXPERIMENTAL | Control arm |
| Name | Type | Description |
|---|---|---|
| AZD3470 | DRUG | AZD3470 is a novel, potent and selective, second-generation, Methylthioadenosine (MTA)-selective, small molecule inhibitor of PRMT5. |
| Pembrolizumab | DRUG | Pembrolizumab (CAS nr: 1374853-91-4 ) |
| Datopotamab deruxtecan | DRUG | AZD3470 in combination with Dato-DXd + Dato-Dxd monotherapy |
Inclusion Criteria: 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 conse...
AZD3470 is an investigational small molecule developed by AstraZeneca PLC (ticker AZN) for oncology. It is being studied in Phase 1 clinical trials as a monotherapy and in combination with other anticancer agents in adults and adolescents with certain advanced solid tumors and hematologic malignancies, including lymphoma.
AZD3470 is being evaluated for the treatment of MTAP deficient advanced solid tumors and for hematologic malignancies including lymphoma, non-Hodgkin lymphoma, Hodgkin lymphoma, peripheral T-cell lymphoma (PTCL), PTCL-NOS, ALCL and AITL. It is investigational and has not been approved for any indication.
AZD3470 is a PRMT5 inhibitor. It targets protein arginine methyltransferase 5 (PRMT5), and its clinical development focuses on MTAP deficient tumors, a biomarker-selected population in which PRMT5 inhibition is being tested as monotherapy and in combination with other anticancer agents.
AZD3470 is developed by AstraZeneca PLC, which trades under the ticker AZN. AstraZeneca is running the Phase 1 clinical program for the drug across sites in the United States, Europe, Asia, Australia and Brazil.
AZD3470 is in Phase 1 clinical development. It is investigational and has not been approved by the FDA or any other regulatory authority. Two Phase 1 trials are currently recruiting, one in MTAP deficient advanced solid tumors and one in hematologic malignancies.
AZD3470 is being studied in two recruiting Phase 1 trials. NCT06130553 evaluates AZD3470 as monotherapy and in combination in patients with MTAP deficient advanced or metastatic solid tumors, with planned enrollment of 334. NCT06137144 evaluates AZD3470 as monotherapy or in combination with anticancer agents in participants with hematologic malignancies, including lymphoma, with planned enrollment of 161.