AZD3470 / AstraZeneca - LARVOL DELTA

CAAP1 loss uncovers vulnerability of MTAP-deficient NSCLC to PRMT5 inhibition with AZD3470 (AACR 2026) - "In summary, CAAP1 deletion in MTAP-null tumors increases sensitivity to AZD3470, both in vivo and in vitro, by potentiating AZD3470 induced cell cycle alterations and DNA damage, potentially through the regulation of alternative splicing."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CAAP1 • MTAP

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