M3554 / EMD Serono - LARVOL DELTA

Evaluating GD2-targeting antibody-drug conjugates for DIPG using human organoid-based preclinical platforms (SNO 2025) - "Future work will assess the efficacy and neurotoxicity of M3554 using our DIPG-brain co-culture model. Successful completion of this study will provide critical preclinical evidence supporting the assessment and use of GD2-targeting ADCs in DIPG treatment."

IO biomarker • Preclinical • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • Solid Tumor • ACVR1 • H3-3A • PPM1D • TP53

PRECLINICAL VALIDATION OF M3554, A NOVEL ANTI-GD2 ANTIBODY-DRUG CONJUGATE, AND EPIGENETIC SENSITIZATION STRATEGIES IN SOFT TISSUE SARCOMAS (CTOS 2025) - P1 | "In this study, we evaluated the preclinical efficacy of M3554 in GD2-expressing STS models and explored the potential of EZH2 inhibition to upregulate GD2 expression as prior findings showed that EZH2 can silence ganglioside biosynthesis genes. GD2 surface expression was assessed via flow cytometry in STS cell lines with or without the EZH2 inhibitor tazemetostat, followed by analysis of ganglioside biosynthetic enzyme expression. M3554 is a promising anti-GD2 ADC with strong preclinical activity in GD2-expressing STS cell lines. Epigenetic modulation using EZH2 inhibition effectively upregulates GD2 expression, potentially enhancing therapeutic response and expanding the range of treatable tumors. These findings support the clinical development of M3554 in STS populations and provide a rationale for combining GD2-targeted therapies with epigenetic modulators."

Preclinical • Brain Cancer • Glioblastoma • Liposarcoma • Neuroblastoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • EZH2

A FIRST-IN-HUMAN PHASE 1, MULTICENTER, OPEN-LABEL STUDY OF M3554, A NOVEL ANTI-GD2 ANTIBODY-DRUG CONJUGATE, IN PATIENTS WITH ADVANCED SOLID TUMORS (CTOS 2025) - P1 | "GD2 is a clinically validated target in pediatric neuroblastoma, however, currently approved anti-GD2 antibodies (e.g., dinutuximab, naxitamab) are associated with severe pain adverse events (AEs), likely due to Fcγ receptor-mediated immune activation via antibody dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC). N/A"

Clinical • First-in-human • Metastases • P1 data • Brain Cancer • Glioblastoma • Neuroblastoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TOP1

Evaluating GD2-targeting antibody-drug conjugates for DIPG using human organoid-based preclinical platforms (WFNOS 2025) - "Future work will assess the efficacy and neurotoxicity of M3554 using our DIPG-brain co-culture model. Successful completion of this study will provide critical preclinical evidence supporting the assessment and use of GD2-targeting ADCs in DIPG treatment."

IO biomarker • Preclinical • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor • ACVR1 • H3-3A • PPM1D • TP53

Anti-GD2 ADC M3554 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Oct 2027 ➔ Mar 2028 | Trial primary completion date: Apr 2026 ➔ Mar 2027

Trial completion date • Trial primary completion date • Solid Tumor

Anti-GD2 ADC M3554 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Trial completion date: Sep 2026 ➔ Oct 2027 | Trial primary completion date: Sep 2026 ➔ Apr 2026

Trial completion date • Trial primary completion date • Solid Tumor

A first-in-human phase 1, multicenter, open-label study of M3554, a novel anti-GD2 antibody-drug conjugate (ADC), in patients with advanced solid tumors (AACR 2025) - P1 | "GD2 is a clinically validated target in pediatric neuroblastoma; however, currently approved anti-GD2 antibody treatments, such as dinutuximab and naxitamab, have been associated with severe adverse events (AEs) of pain, likely due to Fcγ receptor-mediated immune activation via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The study is currently recruiting and aims to enroll 52 patients in the dose escalation phase and 110 patients in the dose expansion phase (STS, n=80; GBM, n=30), across different global sites including, Japan, Belgium, France, and the US. Clinical trial information: NCT06641908."

Clinical • Metastases • P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Neuroblastoma • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Anti-GD2 ADC M3554 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: EMD Serono Research & Development Institute, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

Anti-GD2 ADC M3554 in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=52 | Not yet recruiting | Sponsor: EMD Serono Research & Development Institute, Inc.

Metastases • New P1 trial • Oncology • Solid Tumor

Merck’s Innovative Oncology Pipeline of DNA Damage Response Inhibitors and Antibody-Drug Conjugates Poised to Advance Cancer Treatment (Businesswire) - "Merck...shared updates on the company’s oncology pipeline and focused approach to the research and development of potential new medicines designed to improve the futures of people with cancer...This year, the company plans to open multiple new Phase Ib and II clinical studies for tuvusertib and M9466...updates were shared at the company’s Oncology R&D Update Call...A basket trial planned to launch in early 2025 will further explore M9140 monotherapy in tumors with high CEACAM5 expression, with the potential for further exploration in various combinations...M3554 is the next ADC based on the company’s platform, linking an exatecan payload with an anti-GD2 antibody. This potentially first-in-class ADC will enter its first-in-human study later in 2024."

New P1 trial • New P2 trial • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Osteosarcoma • Ovarian Cancer • Prostate Cancer • Sarcoma • Solid Tumor