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 being studied for advanced solid tumors that are MTAP deficient and for certain lymphomas, including non-Hodgkin lymphoma, Hodgkin lymphoma, and peripheral T-cell lymphoma subtypes. It is being evaluated as a monotherapy and in combination with other anticancer agents in Phase 1 clinical trials.
AZD3470 is a PRMT5 inhibitor. PRMT5 is an enzyme that regulates gene expression by methylating proteins, and its inhibition is being studied as a therapeutic strategy in MTAP-deficient tumors. The drug is designed to exploit the vulnerability of cancer cells that lack the MTAP gene.
AZD3470 is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker symbol AZN. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with advanced solid tumors and hematologic malignancies.
AZD3470 is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The ongoing trials are designed to assess the drug's safety, tolerability, and preliminary efficacy in patients with MTAP-deficient solid tumors and lymphomas.
AZD3470 is being studied in two Phase 1 trials. NCT06130553 evaluates the drug as monotherapy and in combination in patients with MTAP-deficient advanced or metastatic solid tumors, with an enrollment of 334. NCT06137144 studies it as monotherapy or with other agents in hematologic malignancies, including lymphomas, with an enrollment of 161.
Yes, AZD3470 is a PRMT5 inhibitor. PRMT5 stands for protein arginine methyltransferase 5, an enzyme that plays a role in tumor growth. By inhibiting PRMT5, AZD3470 aims to target cancer cells that are deficient in the MTAP gene, which is a common alteration in certain tumors.