Clinical trial NCT06641908: Anti-GD2 ADC M3554 in Advanced Solid Tumors
Official title: A Phase 1, Two-Part, Multicenter, Open-Label First in Human Study of Anti-GD2 Antibody Drug Conjugate M3554 in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: Glioblastoma
IDH-wildtype
Soft tissue sarcomas
GD2 prevalence
targeted therapy
TOP1 inhibitor
exatecan
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
First posted: 2024-10-15
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to establish the recommended doses and further evaluate the safety and preliminary antitumor activity of M3554 in participants with soft tissue sarcoma (STS) and glioblastoma, IDH-wildtype.

Study details include:

Study Duration per participant: Approximately 4 months


Eligibility criteria: Inclusion Criteria:

* Escalation A: participants with documented histopathological diagnosis of locally advanced or metastatic STS with unresectable disease that has progressed after at least one prior line of systemic therapy for the metastatic setting including anthracyclines. Previous trabectidin, eribulin, pazopanib or any other drug approved for the different STS subtypes in second line (2L) or beyond will not be required for enrollment but will be allowed (for example \[e.g\] trabectedin, pazopanib for leiomyosarcoma (LMS); ifosfamide, gemcitabine-based combinations, trabectedin, eribulin, pazopanib for liposarcoma (LPS); trabectedin, gemcitabine, and docetaxel, pazopanib for undifferentiated pleomorphic sarcoma \[UPS\]). Participants with resectable locally advanced or metastatic disease, who had surgery before study entry will be allowed in the trial if there is residual disease after surgery and if the surgery was performed at least 4 weeks before first dose of study intervention.
* Escalation B: participants with documented histopathological diagnosis of glioblastoma, IDH-wildtype, who have progressed after ONLY one prior line of therapy (including radiotherapy +/- temozolomide, depending on the O\^6-methylguanine-DNA methyltransferase \[MGMT\] status) and relapsing at least 3 months after the end of the radiotherapy treatment.
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) below or equal to 1
* Participants with adequate hematologic, hepatic and renal function as defined in protocol
* Other protocol defined inclusion criteria could apply

  * Exclusion Criteria:
* Participant has a history of malignancy other than STS or glioblastoma (depending on the escalation/expansion cohort) within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the Investigator, is considered cured with minimal risk of recurrence within 3 years).
* STS only: Participants with history of brain metastasis, leptomeningeal metastasis, or participants with spinal cord compression
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs)
timeFrame: up to 4 months
Secondary outcomes:
measure: Pharmacokinetic (PK) Plasma Concentrations of M3554
timeFrame: Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
measure: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 or Response Assessment in Neuro-oncology (RANO) 2.0 as Assessed by Investigator
timeFrame: Time from randomization to planned assessment at 4 months
measure: Duration of Response (DoR) According to RECIST Version 1.1 or RANO 2.0 as Assessed by Investigator
timeFrame: Time from randomization to planned assessment at 4 months
measure: Progression-free Survival (PFS) According to RECIST Version 1.1 or RANO 2.0 as Assessed by Investigator
timeFrame: Time from randomization to planned assessment at 4 months
measure: Change from Baseline in Corrected QT Interval (QTc) Interval
timeFrame: Pre-dose on Day 1 (baseline) up to 24 hours post-dose Day 1, Day 2, Day 5, Day 8 of Cycle 1 and Cycle 3 Day 1 (each Cycle is 21 days)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center (MSKCC) - New York - Memorial Sloan Kettering Cancer Center (CC)- Westc
state: New York
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Leuven
country: Belgium
facility: UZ Leuven
city: Bordeaux cedex
country: France
facility: Institut Bergonié - Service d'Oncologie Médicale
city: Lille cedex
country: France
facility: Centre Oscar Lambret - cancerologie generale
city: Lyon
country: France
facility: Centre Leon Berard - Service d'Oncologie Medicale
city: Nice cedex 02
country: France
facility: Centre Antoine Lacassagne - Service d'Hématologie Oncologie
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
Study officials:
affiliation: EMD Serono Research & Development Institute, Inc.
name: Medical Responsible
role: STUDY_DIRECTOR
References: