pivekimab sunirine (PVEK) / AbbVie - LARVOL DELTA

EFFICACY AND SAFETY OF PIVEKIMAB SUNIRINE (PVEK) IN PATIENTS (PTS) WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN) IN THE CADENZA STUDY (EHA 2025) - P1/2 | "Pts with R/R BPDCN had received 1-3 prior systemic therapies; 57% had prior tagraxofusp (TAG). PVEK treatment demonstrated promising efficacy, with high and durable CR + CRc responses, and was tolerable at the RP2D. The safety profile was manageable, with no CLS events, predominantly low-grade peripheral edema, and very low incidence of resolvable VOD, a potential TEAE important to monitor during treatment. These results support PVEK as a potential new treatment option for adult pts with BPDCN."

Clinical • Fatigue • Hematological Malignancies • Hepatology • Oncology • CD123 • IL3RA

Efficacy and safety of pivekimab sunirine (PVEK) in patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the CADENZA study. (ASCO 2025) - P1/2 | "Pts with R/R BPDCN had received 1-3 prior systemic therapies; 57% had prior tagraxofusp. PVEK treatment demonstrated promising efficacy, with high and durable CR + CRc responses. PVEK was tolerable at the RP2D. The safety profile was manageable, with no CLS events."

Clinical • Hematological Malignancies • Hepatology • Oncology • CD123 • IL3RA

Additional oral presentations will highlight new safety and efficacy data for…pivekimab sunirine (PVEK), a novel ADC designed to target CD123 (PRNewswire) - P1/2 | N=179 | CADENZA (NCT03386513) | Sponsor: AbbVie | "Results from the open-label, multicenter Phase 1b/2 CADENZA trial (NCT03386513) of PVEK monotherapy in patients with previously untreated or relapsed/refractory (R/R) blastic plasmacytoid dendritic cell neoplasm (BPDCN), a highly aggressive and rare type of blood cancer, demonstrated clinical benefit. The results show that among 33 untreated patients, the primary endpoint of composite complete response (CCR) rate, defined as CR + clinical CR (CR with minimal skin abnormality), was 70% (95% CI, 51.3-84.4) with a median duration of CCR of 9.8 months. ORR was 85%. In the 51 patients with R/R BPDCN, the CCR rate was 14% with a median duration of CCR of 9.2 months. ORR was 35%....Among all the 84 patients enrolled, the most common grade ≥3 TEAEs were peripheral edema (12%). TEAEs led to discontinuation in 9% and 7% of patients with first-line and R/R BPDCN, respectively. Additional data will be presented at ASCO."

P1/2 data • Hematological Malignancies

Preclinical characterization of the anti-leukemia activity of the CD123 antibody-drug conjugate, pivekimab sunirine (IMGN632). (PubMed, Leukemia) - No abstract available

Journal • Preclinical • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA

IMGN632-0802: IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=218 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Apr 2026 ➔ Feb 2027 | Trial primary completion date: Apr 2026 ➔ Feb 2027

Monotherapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL3RA

Orphan Drug Designations and Approvals (FDA) - Generic Name: pivekimab sunirine, Date Designated: 10/10/2018, Orphan Designation: Treatment of acute myeloid leukemia, Orphan Designation Status: Designated.

Orphan drug • Acute Myelogenous Leukemia

Orphan Drug Designations and Approvals (FDA) - Generic Name: pivekimab sunirine, Date Designated: 11/17/2020, Orphan Designation: Treatment for Blastic Plasmacytoid Dendritic Cell Neoplasm, Orphan Designation Status: Designated.

Orphan drug • Solid Tumor

EU/3/20/2292 - orphan designation for treatment of blastic plasmacytoid dendritic cell neoplasm (European Medicines Agency) - "On 26 June 2020, orphan designation EU/3/20/2292 was granted by the European Commission to ImmunoGen BioPharma (Ireland) Limited, Ireland, for anti-CD123 IgG1 humanised monoclonal antibody conjugated to N1-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-N6-((S)-1-(((S)-1-((3-((((S)-8-methoxy-6-oxo-11,12,12a,13-tetrahydro-6H-benzo[5,6][1,4]diazepino[1,2-a]indol-9-yl)oxy)methyl)-5-((((S)-8-methoxy-6-oxo-12a,13-dihydro-6Hbenzo[5,6][1,4]diazepino[1,2-a]indol-9-yl)oxy)methyl)phenyl)amino)-1-oxopropan-2-yl)amino)-1-oxopropan-2-yl)adipamide (also known as IMGN632) for the treatment of blastic plasmacytoid dendritic cell neoplasm."

Orphan drug • Hematological Malignancies

The CD123 antibody-drug conjugate pivekimab sunirine exerts profound activity in preclinical models of pediatric acute lymphoblastic leukemia. (PubMed, Hemasphere) - "Importantly, a PDX with very high CD123 cell surface expression but resistant to in vivo PVEK treatment, failed to internalize the G4723A antibody while remaining sensitive to the PVEK payload, DGN549, suggesting a novel mechanism of resistance. In conclusion, PVEK was highly effective against a large panel of B-ALL PDXs supporting its clinical translation for B-lineage pediatric ALL."

Journal • Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD123 • IL3RA

CADENZA: Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN (clinicaltrials.gov) - P1/2 | N=179 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Dec 2025 ➔ Dec 2026

Monotherapy • Trial completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • IL3RA

Preclinical Characterization of the Anti-Leukemia Activity of the CD123 Antibody-Drug Conjugate, Pivekimab Sunirine (IMGN632) (ASH 2024) - "Since the above data suggested that TP53 alterations impaired the ability of PVEK to induce cytotoxicity in acute myeloid and lymphoblastic leukemia cells, we used TP53wild-type EOL-1, MOLM-13, MV4; 11, REH, and RS4; 11 cells and deleted TP53 from bulk cells via CRISPR/Cas9 and then exposed these engineered cells to idasanutlin to enrich for the population of TP53KO cells. Important modulators for the drug's cytotoxic effects we identified include CD123 expression levels, TP53 alterations, and overexpression of anti-apoptotic BCL-2 family proteins but surprisingly not activity of ATP transporter proteins. The clinical relevance of these findings should be explored."

IO biomarker • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • BCL2 • BCL2L1 • CD123 • IL3RA

IMGN632-0802: IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=218 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: Dec 2024 ➔ Apr 2026 | Trial primary completion date: Dec 2024 ➔ Apr 2026

Monotherapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL3RA

MODULE 5: Potential Role of Menin Inhibitors and Other Novel Agents in the Treatment of AML (ASH 2024) - "This program is supported by educational grants from AbbVie Inc, Astellas, and Daiichi Sankyo Inc.Mechanism of action of menin inhibitors and rationale for their activity in AML with KMT2 rearrangements and NPM1 mutations Pharmacologic similarities and differences among various menin inhibitors under investigation for AML, such as revumenib, ziftomenib and BMF-219 Early efficacy and safety data with novel menin inhibitors for R/R AML Design, eligibility criteria and available efficacy and safety findings from the pivotal Phase II AUGMENT-101 trial evaluating revumenib for patients with R/R leukemias; efficacy of revumenib for AML with a KMT2 rearrangement FDA breakthrough therapy designation of revumenib; potential role in clinical practice Rationale for targeting CD123 in AML; structural components and mechanism of action of the anti-CD123 antibody-drug conjugate pivekimab sunirine Available data with, ongoing evaluation of and potential clinical role of pivekimab..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA • NPM1

Overcoming Tagraxofusp-Erzs Monotherapy Resistance in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) in a Real-World Clinical Setting. (PubMed, J Immunother Precis Oncol) - "Currently, standard treatment strategies include clinical trials; chemotherapy regimens such as hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD); and tagraxofusp-erzs (TAG, previously SL-401) which is the first-in-class targeted therapy against CD123...However, despite promising results, there are still patients who may be resistant to TAG monotherapy and/or who respond but eventually relapse. Herein, we discuss an important patient case of BPDCN treated with TAG and review BPDCN treatment strategies."

Journal • Monotherapy • Real-world • Real-world evidence • Hematological Disorders • Hematological Malignancies • Oncology • CD123 • IL3RA

CADENZA: Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN (clinicaltrials.gov) - P1/2 | N=179 | Active, not recruiting | Sponsor: ImmunoGen, Inc. | Trial primary completion date: Dec 2024 ➔ Sep 2023

Monotherapy • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • IL3RA

A PHASE 1B/2 STUDY OF PIVEKIMAB SUNIRINE (PVEK, IMGN632) IN COMBINATION WITH VENETOCLAX/AZACITIDINE FOR PATIENTS WITH NEWLY DIAGNOSED CD123-POSITIVE ACUTE MYELOID LEUKEMIA (EHA 2024) - P1/2 | "The PVEK+AZA+VEN triplet in pts with ND unfit AML is currently enrolling across sites in France, Germany, Italy,Spain, UK and USA. Clinical trial information: NCT04086264."

Clinical • Combination therapy • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA

A phase 1b/2 study of pivekimab sunirine (PVEK, IMGN632) in combination with venetoclax/azacitidine for patients with newly diagnosed CD123-positive acute myeloid leukemia. (ASCO 2024) - P1/2 | "Key secondary objectives are safety and tolerability, pharmacokinetics and immunogenicity. The PVEK+AZA+VEN triplet in pts with ND unfit AML is currently enrolling across sites in France, Germany, Italy, Spain, UK and USA."

Clinical • Combination therapy • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA

IMGN632-0802: IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=218 | Active, not recruiting | Sponsor: ImmunoGen, Inc. | Recruiting ➔ Active, not recruiting | Phase classification: P1b/2 ➔ P1/2

Enrollment closed • Monotherapy • Phase classification • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL3RA

Pivekimab sunirine (IMGN632), a novel CD123-targeting antibody-drug conjugate, in relapsed or refractory acute myeloid leukaemia: a phase 1/2 study. (PubMed, Lancet Oncol) - P1/2 | "Pivekimab sunirine showed single-agent activity across multiple doses, with a recommended phase 2 dose of 0·045 mg/kg once every 3 weeks. These findings led to a phase 1b/2 study of pivekimab sunirine plus azacitidine and venetoclax in patients with CD123-positive acute myeloid leukaemia."

Journal • P1/2 data • P2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Neutropenia • Oncology • CD123 • IL3RA

Breakthrough in Blastic Plasmacytoid Dendritic Cell Neoplasm Cancer Therapy Owing to Precision Targeting of CD123. (PubMed, Int J Mol Sci) - "Ongoing developments with SL-401, IMGN632, CD123 chimeric antigen receptor (CAR) T-cells, and bispecific antibodies (BsAb) show promising advancements. The exploration of combinations such as CD123-targeted immunotherapies with azacitidine and venetoclax is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients. In conclusion, this multifaceted approach offers hope for more effective and tailored therapeutic interventions against this challenging hematologic malignancy."

Journal • Review • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Oncology • Transplantation • CD123 • IL3RA

Pivekimab sunirine (PVEK), a CD123 antibody-drug conjugate, exerts profound activity in preclinical models of paediatric acute lymphoblastic leukaemia (NDLR 2024) - No abstract available

Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CD123 • IL3RA

AbbVie Completes Acquisition of ImmunoGen (PRNewswire) - "AbbVie...announced today that it has completed its acquisition of ImmunoGen...With the completion of the acquisition, ImmunoGen is now part of AbbVie...ELAHERE (mirvetuximab soravtansine-gynx) is the first and only antibody-drug conjugate (ADC) approved by the U.S. Food and Drug Administration (FDA) in ovarian cancer...ImmunoGen's investigational Phase 1 asset, IMGN-151, is a next-generation FRα ADC for ovarian cancer with the potential for expansion into other solid tumor indications...Pivekimab sunirine, currently in Phase 2, is an investigational anti-CD123 ADC targeting blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare blood cancer, which was granted FDA breakthrough therapy designation for the treatment of relapsed/refractory BPDCN....AbbVie has acquired all outstanding ImmunoGen common stock for $31.26 per share."

M&A • Gynecologic Cancers • Hematological Malignancies • Oncology • Ovarian Cancer • Solid Tumor

Pivekimab Sunirine (PVEK, IMGN632), a CD123-Targeting Antibody-Drug Conjugate, in Combination with Azacitidine and Venetoclax in Patients with Newly Diagnosed Acute Myeloid Leukemia (ASH 2023) - "Encouraging CCRMRD- rates were observed across cytogenetic/molecular subsets, and the majority of responding pts achieved early and deep remissions, which may translate to improved clinical outcomes. The regimen was well tolerated with no new safety signals, and the addition of PVEK to the AZA-VEN backbone did not appear to meaningfully prolong count recovery."

Clinical • Combination therapy • Acute Myelogenous Leukemia • Constipation • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hepatology • Neutropenia • Renal Disease • CD123 • FLT3 • IDH1 • IDH2 • IL3RA • NPM1

Single-Cell Genomics and Proteomics Reveals Venetoclax-Resistant Monocytic Differentiation of TP53 LOH Clones in TP53 Mutant AML (ASH 2023) - " Patients 1 and 3 received treatment with CD47AB (Magrolimab), 5'-Azacitidine (Aza), and Venetoclax (Ven); Patient 2 received IMGN632 (CD123-targeting ADC), Aza and Ven. Patient 4 received p97 Inhibitor CB-5339; Patient 5 received CD47 inhibitor (ALX148), Aza, Ven... This study establishes a genotype-phenotype connection through single-cell proteogenomic profiling of TP53-mutated AML, describing the clonal evolution and immunophenotypic dynamics during treatment while proposing a potential mechanism of resistance."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • CD123 • CD14 • CD33 • CD34 • CD36 • CD68 • CD8 • EIF4EBP1 • ETV6 • IDH1 • IL3RA • ITGAM • KIT • TP53

Venetoclax Synergizes with IMGN632, a Novel CD123-Targeting Antibody Conjugated to a DNA Alkylating Payload, By Suppressing DNA Damage Response and Potentiating Apoptosis in Acute Myeloid Leukemia in Vitro Models (ASH 2023) - P1/2, P1b/2 | "Importantly, we previously showed high synergy of IMGN632 combination with BCL-2 inhibitor venetoclax (VEN) and DNA hypomethylating azacytidine (AZA) in AML cell lines and xenograft models (ASH 2020, #617). Together, these results suggest that VEN, apart from its canonical inhibitory effect on anti-apoptotic BCL-2, exerts previously unrecognized ability to suppress DDR program in AML and augments activity of DNA damaging IMGN632. Failure of cells to sustain DDR in the presence of VEN constitutes a key aspect of high efficacy of IMGN/VEN/AZA combination in AML."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP3 • CD123 • CHEK1 • FLT3 • IL3RA • MCL1