AZD3470 / AstraZeneca - LARVOL DELTA

TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors, including glioblastoma, with MTAP loss (SNO 2025) - P1/2 | "TNG908, TNG462, AMG 193, BMS-986504, and AZD3470 were the first MTA-cooperative PRMT5 inhibitors entered in clinical trials for the treatment of solid tumors with MTAP loss, though only TNG908 and AMG 193 are reported to be brain-penetrant in preclinical species. TNG456 is currently enrolling patients with MTAP-null solid tumors, including glioblastoma, in a Phase 1/2 clinical study (NCT06810544). With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including glioblastoma and CNS metastases."

Brain Cancer • Glioblastoma • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors, including glioblastoma, with MTAP loss (WFNOS 2025) - P1/2 | "TNG908, TNG462, AMG 193, BMS-986504, and AZD3470 were the first MTA-cooperative PRMT5 inhibitors entered in clinical trials for the treatment of solid tumors with MTAP loss, though only TNG908 and AMG 193 are reported to be brain-penetrant in preclinical species. TNG456 is currently enrolling patients with MTAP-null solid tumors, including glioblastoma, in a Phase 1/2 clinical study (NCT06810544). With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including glioblastoma and CNS metastases."

Brain Cancer • Glioblastoma • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • MTAP

PRIMAVERA: A Modular Phase I/II Study to Evaluate the Safety, Tolerability, and Efficacy of AZD3470, a Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor, in Participants with Relapsed/Refractory Hematologic Malignancies (ASH 2024) - P1/2 | "Participants ≥18 years of age with histologically confirmed, measurable R/R cHL who have received ≥3 prior lines of therapy (including brentuximab vedotin and anti-PD-1 unless not indicated due to toxicity or not accessible) and meet hematologic criteria (Hb ≥10 g/dL, ANC ≥1.5x109/L, platelets ≥100x109/L) will be enrolled. Recruitment for dose escalation (Module 1 Part A) began in January 2024 and is ongoing. The study is planning to enrol across ≈20 sites and is currently enrolling in the following countries : South Korea, Australia, France, Italy, Spain, Germany, UK, and USA."

Clinical • IO biomarker • P1/2 data • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Solid Tumor • MTAP

PRIMROSE: A Study of AZD3470, a PRMT5 Inhibitor, in Patients With MTAP Deficient Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=234 | Recruiting | Sponsor: AstraZeneca | Trial completion date: May 2026 ➔ Feb 2026 | Trial primary completion date: May 2026 ➔ Feb 2026

Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

PRIMAVERA: A PHASE I/II STUDY TO EVALUATE SAFETY AND EFFICACY OF THE PRMT5 INHIBITOR AZD3470 IN PARTICIPANTS WITH RELAPSED/REFRACTORY HEMATOLOGIC MALIGNANCIES (ICML 2025) - P1/2 | "Participants ≥ 18 years of age with histologically confirmed, measurable R/R cHL who have received ≥ 3 prior lines of therapy (including brentuximab vedotin and anti-PD-1 unless contraindicated due to toxicity/accessibility) and meet hematologic criteria (Hb ≥ 10 g/dL, ANC ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L) will be enrolled. Recruitment for dose escalation (Module 1 Part A) is ongoing and study participants have been enrolled across 5 dose levels. The study is planning to enrol across ≈ 20 sites and is currently enrolling in the following countries: South Korea, Australia, France, Italy, Spain, Germany, UK, and USA."

Clinical • IO biomarker • P1/2 data • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • MTAP

PRIMAVERA: A PHASE I/II STUDY TO EVALUATE SAFETY AND EFFICACY OF AZD3470, A PROTEIN ARGININE METHYLTRANSFERASE 5 (PRMT5) INHIBITOR, IN PARTICIPANTS WITH RELAPSED/REFRACTORY HEMATOLOGIC MALIGNANCIES (EHA 2025) - P1/2 | "Participants ≥18 years of age with histologically confirmed, measurable R/R cHL who have received ≥3 prior lines of therapy (including brentuximab vedotin and anti-PD-1 unless contraindicated due to toxicity/accessibility) and meet hematologic criteria (Hb ≥10 g/dL, ANC ≥1.5x109/L, platelets ≥100x109/L) will be enrolled. Exploratory objectives will evaluate the effect of AZD3470 on tumor biomarkers and correlation with response.Recruitment for dose escalation (Module 1 Part A) is ongoing and study participants have been enrolled across 5 dose levels. The study is planning to enrol across ≈20 sites and is currently enrolling in the following countries: South Korea, Australia, France, Italy, Spain, Germany, UK, and USA."

Clinical • IO biomarker • P1/2 data • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Solid Tumor • MTAP

PRIMROSE: A Study of AZD3470, a PRMT5 Inhibitor, in Patients With MTAP Deficient Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=234 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Feb 2026 ➔ May 2026 | Trial primary completion date: Feb 2026 ➔ May 2026

Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors with MTAP loss (AACR 2025) - "TNG908, TNG462, AMG 193, BMS-986504, and AZD3470 are clinical-stage MTA-cooperative PRMT5 inhibitors for the treatment of solid tumors with MTAP loss, though only TNG908 and AMG 193 are reported to be brain-penetrant. Oral administration of TNG456 drives dose-dependent antitumor activity including durable tumor regressions and complete responses in multiple cell line- and patient-derived xenograft models. With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including gliomas and CNS metastases."

Brain Cancer • CNS Tumor • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MTAP

TRIAL IN PROGRESS: PRIMAVERA: A MODULAR PHASE I/II STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND EFFICACY OF AZD3470, A PROTEIN ARGININE METHYLTRANSFERASE 5 (PRMT5) INHIBITOR, IN PARTICIPANTS WITH RELAPSED/REFRACTORY (R/R) HEMATOLOGIC MALIGNANCIES (ISHL 2024) - P1/2 | "Participants ≥18 years of age with measurable R/R cHL who have received ≥3 prior lines of therapy (including brentuximab vedotin and anti-PD-1) and meet hematologic criteria (Hb ≥10 g/dL, ANC ≥ 1.5 × 109/L, platelets ≥100 × 109/L) will be enrolled. Exploratory objectives will evaluate the effect of AZD3470 on tumor biomarkers and correlation with response.Recruitment for dose escalation (Module 1 Part A) began in January 2024 and is ongoing. The study is planning to enrol across ≈20 sites and is currently enrolling in the following countries: South Korea, Australia, France, Italy, Spain, Germany, UK, and USA."

Clinical • IO biomarker • P1/2 data • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Solid Tumor • MTAP

First disclosure of AZD3470, a highly potent MTA-cooperative PRMT5 inhibitor in PRIMROSE and PRIMAVERA clinical studies (EORTC-NCI-AACR 2024) - P1/2 | "These studies show that AZD3470 is a highly potent and selective PRMT5 inhibitor that induces strong anti-tumor efficacy in pre-clinical models at exposures that result in minimal hematotoxicity. These results support the potential of this compound to have high clinical efficacy for the treatment of MTAP-deficient cancers."

Clinical • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Solid Tumor • MTAP

AZD3470 induces regressions and durable responses in MTAP-deficient tumor models of diverse tumor indications (EORTC-NCI-AACR 2024) - P1/2 | "These data demonstrate that AZD3470, currently in Ph1 clinical trials, has the potential to show robust clinical activity across a broad range of solid cancer indications."

Preclinical • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN2A • MTAP

PRIMROSE: A modular phase 1/2a study of AZD3470, an MTA-cooperative PRMT5 inhibitor, in patients with MTAP deficient advanced solid tumors. (ASCO 2024) - P1/2 | "The study is planned to take place in ~20 centers across eight countries. The study was opened to enrollment in December 2023."

Clinical • Metastases • P1/2 data • Oncology • Solid Tumor • MTAP • PRMT5

Integrative dynamic MultiOMICs analysis identifies cell cycle and DNA damage response phenotypes as downstream consequences of using the PRMT5 inhibitor AZD3470 (AACR 2024) - P1/2 | "Here we identify AZD3470-induced changes to protein post-translational modification, chromatin accessibility, gene expression and RNA splicing in MTAP-deficient NSCLC cancer cell lines. Different area of MultiOMICs data together pointed to changes in cell cycle and DNA repair pathways. Further, we identified alternative splicing of ATM as a consequence of AZD3470 PRMT5i treatment resulting in significant reduction of ATM protein expression."

Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ATM • CDK6 • MTAP

PRIMAVERA: AZD3470 as Monotherapy and in Combination With Anticancer Agents in Participants With Relapsed/Refractory Haematologic Malignancies. (clinicaltrials.gov) - P1/2 | N=110 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Monotherapy • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

PRIMROSE: A Study of AZD3470, a PRMT5 Inhibitor, in Patients With MTAP Deficient Advanced/Metastatic Solid Tumours (clinicaltrials.gov) - P1/2 | N=210 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor