Table 1.
Available TCR T trial results.
| Ref | Year | Trial | Phase | Sponsor | Target | HLA | Construct Details | Disease | # Pts | Pre. Cond. | Combination | Responses | TCR T Induced Toxicity |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (124) | 2011 | NCT00923806 | I/II | NCI | CEA | A*02:01 | affinity enhanced TCR | colorectal cancer | 3 pts | Cy + Flu | IL-2 | 1/3, 33.3% (ORR/PR) | Severe colitis (3 pts) |
| (126) | 2009 | NCT00509496 | II | NCI | gp100 | A*02:01 | melanoma | 16 pts | Cy + Flu | IL-2 |
3/16, 18.8% (ORR)
1/16 (CR), 2/16 (PR) |
Skin toxicity (15 pts), Uveitis (4 pts), Hearing loss (5 pts) | |
| (171) | 2006 | Not Specified (NS) | NS | NS | MART-1 | A*02:01 | DMF4 TCR | melanoma | 17 pts | Cy + Flu | IL-2 Peptide vaccine |
2/17, 12% (ORR/PR)
1/17 (MR) |
None |
| (126) | 2009 | NCT00509288 | II | NCI | MART-1 | A*02:01 | DMF5 TCR | melanoma | 20 pts | Cy + Flu | IL-2 | 6/20, 30% (ORR/PR) | Skin toxicity (14 pts), Uveitis (12 pts), Hearing loss (10 pts) |
| (172) | 2014 | NCT00910650 | II | JCCC | MART-1 | A*02:01 | DMF5 TCR | melanoma | 10 pts | Cy + Flu | IL-2 Peptide-pulsed DC vaccine |
0/14, 0% (ORR)
7/14 (SD) ORR assessed at Day 90 |
Erythematous skin rash (3 pts), Acute respiratory distress (2 pts) |
| (173) | 2018 | NCT01586403 | I | Loyola University | tyrosinase | A*02 | TIL1383I TCR | melanoma | 3 pts | Cy + Flu | IL-2 | 1/3, 33% (ORR/PR) | Vitiligo (2 pts) |
| (174) | 2015 | NCT00670748 | II | NCI | NY-ESO-1 | A*02:01 | 1G4-a95:LY TCR (affinity enhanced) | melanoma synovial sarcoma | 38 pts | Cy + Flu | IL-2 ± AVIPOX- ESO vaccine |
22/38, 58% (ORR)
5/38 CR, 17/38 PR |
None |
| (175) | 2019 | NCT02366546 | I | Mie University | NY-ESO-1 | A*02:01 A*02:06 |
affinity enhanced TCR siRNA TRAC/TRBC | various solid tumors | 9 pts | Cy | None | 3/9, 33.3% (ORR/PR) | CRS (3 pts) |
| (176) | 2019 |
NCT02070406 NCT01697527 |
I | JCCC | NY-ESO-1 | A*02:01 | 1G4-a95:LY TCR (affinity enhanced) | various solid tumors | 10 pts | Cy + Flu | IL-2, DC-peptide vaccine, ± ipilimumab |
2/10, 20% (ORR)
1/10 (CR), 1/10 (PR), 4/10 (tR) |
None |
| (177) | 2019 | NCT02869217 | Ib | University Health Network | NY-ESO-1 | A*02:01 A*02:06 |
TBII-1301 (MS3II-NY-ESO1-SiTCR) | various solid tumors | 9 pts | Cy | None |
2/9, 22.2% (ORR/PR)
5/9 (SD), 1 pending |
CRS grade 1-2 (5 pts) |
| (178) | 2019 | NCT01352286 | I/IIa | GlaxoSmithKline | NY-ESO-1/LAGE-1 | A*02:01 | NY-ESO-1 SPEAR T cells (NY-ESOc259 TCR) | multiple myeloma (Post-HSCT) | 25 pts | melphalan | lenalidomide |
21/25, 84% (ORR)
2/25 (sCR), 1/25 (CR), 13/25 (VGPR), 5/25 (PR), 4/25 (SD) |
GVHD (6 pts). Likely not related to the engineered TCR. |
| (179) | 2019 | NCT01343043 | I/II | GlaxoSmithKline | NY-ESO-1 | A*02 | NY-ESO-1 SPEAR T cells | synovial sarcoma | 42 pts | Cy ± Flu as per cohort | None |
15/42, 35.7% (ORR)
1/42 (CR), 14/42 (PR), 24/42 (SD) |
CRS grades 1 (2 pts), 2 (1 pts), and 3 (2 pts) |
| (164) | 2020 | NCT03399448 | I | University of Pennsylvania | NY-ESO-1 | A*02:01 | 8F TCR, CRISPR KO TRAC/TRBC/PDCD1 | multiple myeloma, MRCLS | 3 pts | Cy + Flu | None |
0/3, 0% (ORR)
2/3 (SD) |
None |
| (128) | 2013 |
NCT01350401 NCT01352286 |
I/II | Adaptimmune GlaxoSmithKline |
MAGE-A3 | A*01 | MAGE-A3a3a TCR (affinity enhanced) | melanoma, myeloma (Post-ASCT) | 2 pts | Cy (melanoma pts) | None | NA | Off-target toxicity in cardiac tissue leading to 2 pt deaths |
| (129) | 2013 | NCT01273181 | I/II | NCI | MAGE-A3 | A*02:01 | affinity enhanced TCR | various solid tumors | 9 pts | Cy + Flu | IL-2 |
5/9, 55.6% (ORR)
1/9 (CR), 4/9 (PR) |
Neurological toxicity (3 pts) 2 pt deaths. |
| (194) | 2017 | NCT02111850 | I/II | NCI | MAGE-A3 | DPB1*04:01 | various solid tumors | 17 pts | Cy + Flu | IL-2 |
4/17, 23.5% (ORR)
1/17 (CR), 3/17 (PR) |
Fever (10 pts), Elevated ALT, AST, and creatinine (2 pts) | |
| (181) | 2015 | UMIN000002395 | I | Mie University | MAGE-A4 | A*24:02 | esophageal cancer | 10 pts | None | Peptide vaccine |
0/10, 0% (ORR/PR)
3/10 SD |
None | |
| (182) | 2020 | NCT03132922 | I | Adaptimmune | MAGE-A4 | A*02 | ADP-A2M4 SPEAR T cells | various solid tumors | 34 pts | Cy + Flu | None |
7/28, 25% (ORR/PR)
11/28 (SD) |
2 pt related deaths (aplastic anemia and CVA), not likely off target toxicity |
| (183) | 2020 | NCT04044859 | I | Adaptimmune | MAGE-A4 | A*02 | ADP-A2M4CD8 SPEAR T cells | various solid tumors | 5 pts | Cy + Flu | None |
2/5, 40% (ORR/PR)
3/5 (SD) |
No DLTs or SAEs |
| (184) | 2021 | NCT04044768 | II | Adaptimmune | MAGE-A4 | A*02 | ADP-A2M4 SPEAR T cells | synovial sarcoma, MRCLS | 37 pts | Cy + Flu | None |
13/33, 39% (ORR)
11/33 (PR), 2/33 (CR), 15/33 (SD) |
CRS grades 1-2 (21 pts), 3 (1 pt) |
| (185) | 2018 |
NCT02989064 NCT02592577 |
I | Adaptimmune | MAGE-A10 | A*02 | MAGE-A10c796 TCR (affinity enhanced) |
various solid tumors | 8 pts | Cy ± Flu | None | 0/8, 0% (ORR/PR) | CRS (1 pt), Increase in serum amylase (1 pt) |
| (186) | 2019 | NCT02280811 | I/II | NCI | E6 | A*02:01 | E6 TCR | HPV-associated solid cancers | 12 pts | Cy + Flu | IL-2 |
2/12, 16.7% (ORR/PR)
4/12 (SD) |
None |
| (44) | 2021 | NCT02858310 | I | NCI | E7 | A*02:01 | E7 TCR | HPV-associated carcinomas | 12 pts | Cy + Flu | IL-2 |
6/12, 50% (ORR/PR)
4/12 (SD) |
1 DLT, not likely off target toxicity |
| (187) | 2017 | UMIN000011519 | I | Several sponsors | WT1 | A*24:02 | TAK-1 TCR, siTCR | AML, MDS | 8 pts | None | Peptide vaccine | Transient decrease of blasts in BM in 2 pts. SD in 1 pt. | No adverse events greater than grade 3 |
| (188) | 2019 | NCT01640301 | I/II | Fred Hutchinson CRC | WT1 | A*02:01 | TCRC4, Allo EBV-specific T cells | AML (Post-HCT) | 12 pts | None | IL-2 | 100% RFS vs 54% in comparative group | GVHD in several patients, not likely caused by TCR T cells, but rather HCT. |
NA, Not Applicable. Bolded values highlight the overall response rates of the trials.