Cutaneous Melanoma, Synovial Sarcoma
Conditions
Keywords
immunotherapy, T-cell therapy, cutaneous melanoma, synovial sarcoma, RNA vaccine, Immatics, Moderna
Brief summary
This purpose of this clinical trial is to evaluate the safety, tolerability and anti-tumor activity of IMA203 in combination with different doses of mRNA-4203. The trial includes participants with previously treated unresectable or metastatic cutaneous melanoma (CM) or synovial sarcoma (SS).
Detailed description
This clinical trial is a multi-center, open-label, non-comparative Phase 1 a/b trial to assess the safety, tolerability, and anti-tumor activity of the combination of IMA203 and mRNA-4203 in HLA-A\*02:01 positive patients with previously treated, unresectable or metastatic cutaneous melanoma (CM) and synovial sarcoma (SS).
Interventions
BIOLOGICALIMA203
Following non-myeloablative chemotherapy for lymphodepletion (LD) with fludarabine (FLU) and cyclophosphamide (CY), participants will receive a single infusion of IMA203 on Day 1 and adjunctive therapy with low dose interleukin (IL)-2 for up to 10 days, starting approximately 24 h after IMA203 infusion.
BIOLOGICALmRNA-4203
mRNA-4203 will be administered starting on Day 15 after IMA203 infusion at the earliest. mRNA-4203 will be given for 12 cycles (28 day cycle length); during Cycle 1 it will be given on Day 1 and Day 15 and in Cycles 2-12 it will be given on Day 1.
Sponsors
ModernaTX, Inc.
Immatics US, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed and documented cutaneous melanoma (CM) or synovial sarcoma (SS) with unresectable or metastatic disease * HLA-A\*02:01 positive * Adequate selected organ function per protocol * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) * Life expectancy more than 5 months * CM participants who must have disease progression (resistance, toxicity) on or after at least one PD-1 inhibitor * SS participants must have received (or declined) at least one line of treatment (including SoC) and are still in need of further systemic therapy. * Female participants of childbearing potential must use adequate contraception prior to trial entry until 12 months after the infusion of IMA203 and 15 days after the last mRNA 4203 dose administration Other protocol defined inclusion criteria could apply
Exclusion criteria
* History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years * Pregnant or breastfeeding * Serious autoimmune disease * History of cardiac conditions as per protocol * Prior allogenic stem cell transplantation or solid organ transplantation * Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study * History of hypersensitivity to cyclophosphamide, fludarabine, or IL-2 * History of hypersensitivity to mRNA-based medicines * Positive for HIV infection or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection * Any condition contraindicating leukapheresis * Participants with lactate dehydrogenase (LDH) greater than threshold allowed per protocol * Participants with active brain metastases prior to lymphodepletion * Concurrent treatment in another clinical trial or a device trial that could interfere with the IMA203 treatment * Participants with renal impairment AND reduced bone marrow reserve per protocol Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with dose-limiting toxicities (DLTs) | one year post infusion of IMA203 | Number of DLTs will be used to determine the maximum tolerated dose (MTD) and/or recommended dose for extension (RDE) after treatment with IMA203 product in combination with mRNA-4203 |
| Number of treatment emergent adverse events (AEs), AEs of special interest, serious AEs (SAEs), changes in laboratory parameters and vital signs, and frequency of dose interruptions, reductions and discontinuations | one year post infusion of IMA203 | Used to evaluate safety and tolerability of treatment with IMA203 in combination with mRNA-4203 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | one year post infusion of IMA203 | CR, PR and stable disease (SD) lasting 6 or more weeks following the infusion of IMA203, locally assessed using RECIST v1.1 |
| Objective response rate (ORR) | one year post infusion of IMA203 | complete response (CR) and partial response (PR) based on best overall response (BOR), locally assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
| Concentration of IMA203 transgene in peripheral blood | one year post infusion of IMA203 | Evaluate the pharmacokinetics of T-cell receptor (TCR) engineered T cells in combination with mRNA-4203 |
| Progression-free survival (PFS) | one year post infusion of IMA203 | locally assessed using RECIST v1.1 |
| Duration of response (DOR) | one year post infusion of IMA203 | CR and PR, locally assessed using RECIST v1.1 |
Countries
United States
Contacts
Primary ContactImmatics US, Inc.
Outcome results
None listed