Advanced Solid Tumor, Metastatic Solid Tumor, Solid Carcinoma, Solid Tumor, Unresectable Solid Tumor
Conditions
Keywords
Solid Tumor, Solid Carcinoma, Advanced Solid Tumor, Unresectable Solid Tumor, Metastatic Solid Tumor, MSK-TCR5, Memorial Sloan Kettering Cancer Center, 26-083
Brief summary
The purpose of this study is to test the safety of MSK-TCR5 in participants with advance solid tumor cancer that has a KRAS, HRAS, or NRAS G12D mutation.
Interventions
BIOLOGICALMSK-TCR5
MSK-TCR5, created in participant-derived T cells and autologously reinfused into eligible participants following lymphodepleting chemotherapy
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part A: Prior to cell collection all of the following inclusion criteria must be met: * Age ≥18 years. * Histologically confirmed advanced or metastatic, unresectable solid tumor * Positive for RAS G12D mutation and HLA-A\*11:01 allele * Subject has advanced solid cancer, defined as unresectable, advanced, and/or metastatic disease after at least 1 line of systemic standard of care (SOC) treatment regimen and for which there are no available curative treatment options. Subjects with stable disease (SD), or that present lack of clinical benefit from previous therapy (including treatment suspension due to toxicity) may be considered eligible for enrollment. : 1. For CRC: Patients harboring genomic aberrations such as BRAFV600E mutations, HER2 amplifications, or VEGF expression for which FDA-approved targeted therapies are available must have received prior treatment with applicable FDA-approved targeted therapies, including multi-kinase inhibitors. Patients whose tumors have deficient mismatch repair (dMMR)/high microsatellite instability (MSI-H) must have received an immune checkpoint inhibitor prior to enrolling in this study. 2. For NSCLC: Patients harboring genomic aberrations such as non-resistant EGFR mutations, ALK rearrangement, ROS rearrangement, and BRAF V600E mutation for which FDA-approved targeted therapies are available must have received prior treatment with the applicable FDA-approved targeted therapies. Patients with the appropriate PD-L1 expression score must have received treatment with an FDA-approved checkpoint inhibitor with or without chemotherapy consistent with the FDA-approved label. 3. Any other solid tumors, including PDAC: Patients harboring genomic aberrations for which FDA-approved targeted therapies are available must have received prior treatment with the applicable FDA-approved targeted therapies. Patients whose tumors have dMMR/MSI-H must have received an immune checkpoint inhibitor prior to enrolling in this study. Part B: Prior to treatment with MSK-TCR5 all of the following inclusion criteria must be met: * Measurable disease per RECIST version 1.1. Note: a previously irradiated or locoregionally treated lesion can be considered a target lesion if it progressed post-treatment. * ECOG performance status of 0 or 1 * Adequate organ and bone marrow function based on the following laboratory values: 1. ANC ≥1000/mm3 without granulocyte colony-stimulating factor support (filgrastim within 7 days or peg-filgrastim within 14 days of screening) 2. Platelets ≥75,000/mm3 without transfusion within the preceding 7 days of screening. 3. Hemoglobin ≥8.0 g/dL (≥80 g/L); blood transfusion permitted within 7 days of screening. 4. AST, ALT, and ALP ≤ 3x ULN, or ≤ 5x ULN if liver or bone metastases present. 5. Total bilirubin ≤ 1.5x ULN or ≤ 3x ULN in the presence of documented Gilbert's Syndrome 6. CrCl ≥50 mL/min by Cockcroft-Gualt equation
Exclusion criteria
Part A: Participant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of related toxicities | 1 year | Primary objective is to evaluate the safety of MSK-TCR5. Safety will be measured by the primary endpoint of the occurrence and nature of AEs per participants. AEs will be defined as DLTs and events according to the CTCAE v5.0, with the exception of CRS and ICANS, which will be according to the ASTCT consensus criteria. |
Countries
United States
Contacts
CONTACTAdam Schoenfeld, MD
CONTACTChristopher Klebanoff, MD
PRINCIPAL_INVESTIGATORAdam Schoenfeld, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed