Advanced Solid Tumor
Conditions
Keywords
Glioblastoma, IDH-wildtype, Soft tissue sarcomas, GD2 prevalence, targeted therapy, TOP1 inhibitor, exatecan
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
Interventions
DRUGM3554
M3554 will be administered at an escalated dose until Maximum tolerated dose (MTD) and/or a safe recommended Dose is determined in participants with STS (dose escalation A) and glioblastoma and IDH wildtype (dose escalation B).
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 anthracycline-containing systemic therapy for the locally advanced/metastatic setting. * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs) | up to 4 months |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic (PK) Plasma Concentrations of M3554 | 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 |
| 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 | Time from randomization to planned assessment at 4 months |
| Duration of Response (DoR) According to RECIST Version 1.1 or RANO 2.0 as Assessed by Investigator | Time from randomization to planned assessment at 4 months |
| Progression-free Survival (PFS) According to RECIST Version 1.1 or RANO 2.0 as Assessed by Investigator | Time from randomization to planned assessment at 4 months |
| Change from Baseline in Corrected QT Interval (QTc) Interval | 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) |
Countries
Belgium, France, Japan, Switzerland, United Kingdom, United States
Contacts
CONTACTUS Medical Information
CONTACTCommunication Center
STUDY_DIRECTORMedical Responsible
EMD Serono Research & Development Institute, Inc.
Outcome results
None listed