TABLE 1:
Selected clinical trials using TCR ACT for cancera
| Target, sequenceb | HLA | TCR; affinity-matured (yes/no/not specified); KD (if known) | Cancer(s)c | No. of patientsd | Trial phase | Responsee; trial status | Sponsor,f country | Trial ID, start date | |
|---|---|---|---|---|---|---|---|---|---|
| 1 | p53:264–272; LLGRNSFEV | HLA-A*02:01 | p53 TCR; no74,75 | Metastatic melanoma and other metastatic cancers | 12 | II | No information | NCI, USA | NCT00393029, Oct 2006 |
| 2 | p53 | HLA-A*02:01 | p53 TCR; not specified | Progressive or recurrent metastatic cancer | 3 | II | Terminated (withdrawal of collaborators’ support) | NCI, USA | NCT00704938, June 2008 |
| 3 | MART-1, AAGIGILTV | HLA-A*02:01 | DMF4; no; KD = 170 μM63 | Metastatic melanoma | 15 | — | 13% OR (2/15) | NCI, USA | See ref. 62 |
| 4 | MART-1, AAGIGILTV | HLA-A*02:01 | DMF5; yes; KD = 40 μM63 | Metastatic melanoma | 20 | II | 30% OR (6/20); 55% uveitis (11/20); 50% hearing loss (10/20) | NCI, USA | NCI-07-C-0175, NCT00509288, June 200743 |
| 5 | MART-1, AAGIGILTV | HLA-A*02:01 | DMF5; yes; KD = 40 μM63 | Metastatic melanoma | 1 | I, II | Terminated (low accrual) | NCI, USA | NCT00924001, Aug 2007 |
| 6 | MART-1, AAGIGILTV | HLA-A*02:01 | DMF5; yes; KD = 40 μM63 | Metastatic melanoma | 4 | II | Terminated (low accrual) | NCI, USA | NCT00612222, Jan 2008 |
| 7 | MART-1 | HLA-A*02:01 | DMF5; yes; KD = 40 μM63 | Melanoma | 50 | II | Terminated (low enrollment) | NCI, USA | NCT00706992, June 2008 |
| 8 | MART-1 | HLA-A*02:01 | DMF5; yes; KD = 40 μM63 | Metastatic melanoma | 13 | II | 69% tumor regression (9/13); 38% progressive disease (5/13); 54% stable disease (7/13) | JCCC (UCLA), USA | NCT00910650, Oct 200976,77 |
| 9 | MART-1:26–35, EAAGIGILTV | HLA-A*02:01 | 1D3 HM CysTCR; no78 | Stage IV skin melanoma, eye melanoma | 12 | I, II | Active, not recruiting, no results posted | Netherlands Cancer Institute, Netherlands | NCT02654821, Mar 201279 |
| 10 | gp100, KTWGQYWQV | HLA-A*02:01 | gp100154 mouse TCR; no | Metastatic melanoma | 16 | II | 19% OR (3/16); 25% uveitis (4/16); 31% mild hearing loss (5/16); Terminated | NCI, USA | NCI-07-C-0174, NCT00509496, June 200743 |
| 11 | NY-ESO-1: 157–165, SLLMWITQC | HLA-A*02:01 | 1G4-α95:LY; yes; KD = 730 nM80 | Metastatic SCS, metastatic melanoma, metastatic SCS, metastatic melanoma | Metastatic SCS: 6; metastatic melanoma: 11; metastatic SCS: 18; metastatic melanoma: 20 | II | Metastatic SCS: 66% OR (4/6); metastatic melanoma: 16% PR (1/6); metastatic SCS: 45% OR (5/11); metastatic melanoma: 18% CR (2/11), 61% OR (11/18), 55% OR (11/20) | NCI, USA | NCT00670748, April 200864; NCT00670748, April 200865 |
| 12 | NY-ESO-1/LAGE-1: SLLMWITQC | HLA-A*02:01 | NY-ESO-1c259; yes; KD = 730 nM81 | Multiple Myeloma | 20 | I, II | 70% nCR/CR (14/20); 10% VGPR (2/20); 10% PR (2/20); active, not recruiting | GSK, USA | NCT01352286, May 201166 |
| 13 | NY-ESO-1 | HLA-A*02:01 | NY-ESO-1c259; yes; KD = 730 nM81 | Melanoma | 4 | I, II | Terminated (lack of enrollment) | Adaptimmune, USA | NCT01350401, June 2011 |
| 14 | NY-ESO-1/LAGE-1,SLLMWITQC | HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 | NY-ESO-1c259; yes; KD = 730 nM81 | Metastatic SCS | 12 | I | 50% OR (6/12); 42% PR (5/12); 8% CR (1/12); Recruiting | GSK, USA | NCT01343043, Sep 201282,83 |
| 15 | NY-ESO-1:157–165, SLLMWITQC | HLA-A*02:01 | NY-ESO-1 TCR; not specified | Malignant neoplasm | 22 (est.) | II | Recruiting | JCCC (UCLA), USA | NCT01697527, Nov 2012 |
| 16 | NY-ESO-1:157–165, SLLMWITQC | HLA A*02:01, HLA-A*02:05, and/or HLA-A*02:06 | NY-ESO-1c259; yes; KD = 730 nM81 | Ovarian | 6 | II | 0% response (not recruiting) | Adaptimmune, USA | NCT01567891, Jul 2013 |
| 17 | NY-ESO-1 and/or LAGE-1 | HLA-A*02:01 | NY-ESO-1c259; yes; KD = 730 nM81 | Multiple myeloma | 6 | I, II | Terminated (sponsor decision) | Adaptimmune, USA | NCT01892293, Oct 2013 |
| 18 | NY-ESO-1 | HLA-A*02:01 | NY-ESO-1 TCR with murine chains; no84 | Melanoma, meningioma, breast cancer, NSCLC, HCC | 43 | II | Recruiting | NCI, USA | NCT01967823, Oct 2013 |
| 19 | NY-ESO-1 | HLA-A*02:01 | NY-ESO-1 TCR; not specified | Metastatic melanoma | 2 | II | Terminated (low accrual) | NCI, USA | NCT02062359, Feb 2014 |
| 20 | NY-ESO-1:157–165 | HLA-A*02:01 | NY-ESO-1 TCR; not specified | Solid cancers | 4 | I | Terminated (low accrual) | JCCC (UCLA), USA | NCT02070406, Jul 2014 |
| 21 | NY-ESO-1 | HLA-A*02:01 or HLA-A*02:06 | NY-ESO-1 TCR (TBI-1301); not specified | Solid cancers | 9 | I | Active, not recruiting | Mie University, Japan | NCT02366546, Mar 2015 |
| 22 | NY-ESO-1 | HLA-A* 02 | NY-ESO-1 TCR; not specified | Solid cancers | 36 (est.) | 1 | Recruiting | Shenzhen Second People’s Hospital, China | NCT02457650, Apr 2015 |
| 23 | NY-ESO-1 | HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 | NY-ESO-1c259; yes; KD = 730 nM81 | Advanced (stage IIIb or IV) NSCLC | 10 (est.) | I | Recruiting | GSK, USA | NCT02588612, Feb 201685 |
| 24 | NY-ESO-1 | HLA-A*02:01 | NY-ESO-1 TCR with murine chains; no84 | Metastatic cancers | 10 (est.) | — | Recruiting | Albert Einstein College of Medicine, USA | NCT02774291, Aug 2016 |
| 25 | NY-ESO-1 | Not specified | NY-ESO-1 TCR; not specified | Advanced malignant solid tumors | 15 (est) | — | Recruitment status unknown | Fudan University, China | NCT03047811, Aug 2016 |
| 26 | NY-ESO-1 | HLA-A*02:01, HLA-A*02:06 | NY-ESO-1 TCR (TBI-1301); not specified | Solid cancers | 15 (est.) | I | Recruiting | University Health Network, Canada | NCT02869217, Sep 2016 |
| 27 | NY-ESO-1 | HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06 | NY-ESO-1c259; yes; KD = 730 nM81 | Advanced MRCLS | 10 (est.) | II | Recruiting | GSK, USA | NCT02992743, Dec 2016 |
| 28 | NY-ESO-1:157–165 | HLA-A*02:01 | NY-ESO-1 TCR; not specified | Stage IV or locally advanced solid tumors | 12 (est.) | I | Recruiting | JCCC (UCLA), USA | NCT02775292, Jan 2017 |
| 29 | NY-ESO-1 | HLA-A2*02:01 | NY-ESO-1 TCR TAEST16001; yes | Advanced NSCLC | 20 (est.) | I | Recruiting | Guangzhou Institute of Respiratory Disease, China | NCT03029273, Mar 2017 |
| 30 | NY-ESO-1 | HLA-A2*02:01 | NY-ESO-1 TCR TAEST16001; yes | Solid tumors | 20 (est.) | I | Recruiting | Zhujiang Hospital, China | NCT03159585, Apr 2017 |
| 31 | NY-ESO-1 | HLA-A*02:01 | NY-ESO-1 TCR; not specified | Stage IV or locally advanced unresectable cancers | 12 (est.) | I | Recruiting | JCCC (UCLA), USA | NCT03240861, July 2017 |
| 32 | NY-ESO-1 /LAGE-1 | HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 | NY-ESO-1c259; yes; KD = 730 nM81 | Multiple myeloma | 24 (est) | II | Recruiting | GSK, USA | NCT03168438,Aug 2017 (Follow-up; see ref. 83) |
| 33 | NY-ESO-1:157–165, SLLMWITQC | HLA-A*02:01 and HLA-A*02:06 | NY-ESO-1 TCR; not specified | SCS | 8 (est.) | I, II | Recruiting | Takara Bio Inc., Japan | NCT03250325, Sep 2017 |
| 34 | NY-ESO-1 | HLA-A*02:01 | NY-ESO-1 TCR with murine chains; no84 | Recurrent or refractory ovarian, primary peritoneal, or fallopian tube carcinoma | 12 (est.) | I | Recruiting | Roswell Park Cancer Institute, USA | NCT03017131, Dec 2017 |
| 35 | NY-ESO-1 | Not specified | NY-ESO-1c259(GSK3377794); yes; KD = 730 nM81 | — | 200 (est.) | I | Recruiting | GSK, USA | NCT03391778, Apr 2018 (long-term follow-up of subjects exposed to NY-ESO-1c259 T cells) |
| 36 | NY-ESO-1 | HLA-A2*02:01 | NY-ESO-1 TCR TAEST; yes | Sarcoma | 20 (est.) | I | Recruiting | Sun Yat-sen University, China | NCT03462316, May 2018 |
| 37 | NY-ESO-1 | HLA-A*02:01 | NY-ESO-1 TCR (NYCE T cells); not specified | Multiple myeloma, melanoma, SCS, MRCLS | 18 (est.) | I | Recruiting | UPenn, USA | NCT03399448, Sep 2018 |
| 38 | NY-ESO-1/LAGE-la | HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 | NY-ESO-1c259(GSK3377794); yes; KD = 730 nM81 | NSCLC | 44 (est.) | II | Recruiting | MSD, USA | NCT03709706, Dec 2018 |
| 39 | NY-ESO-1 | HLA-A*02:01 and HLA-DP*04 | NY-ESO-1 TCR; not specified | Recurrent or refractory ovarian, fallopian tube, or primary peritoneal cancers | 15 (est.) | I | Recruiting | Roswell Park Cancer Institute, USA | NCT03691376, Jan 2019 |
| 40 | CEA, IMIGVLVGV | HLA-A*02:01 | PG13-CEA mouse TCR; yes86 | Metastatic CRC | 3 | I | 33% OR (1/3); 100% colitis (3/3) (CEA on normal colon mucosa); Terminated | NCI, USA | NCT00923806, Dec 200844 |
| 41 | TRAIL/DR4 | HLA-independent | 2G-1 TCR; no87 | Metastatic renal cancer | 5 | I, II | Terminated | NCI, USA | NCT00923390, Mar 2009 |
| 42 | MAGE-A3, KVAELVHFL, MAGE-A12, KMVELVHFL | HLA-A*02:01 | PG13-MAGE-A3 TCR9W11; yes88 | Metastatic melanoma, SCS, esophageal cancer | 9 | I, II | 11% CR (1/9); 44% PR (4/9); 22% neurotoxicity (2/9) (MAGEA12 in brain); Terminated | NCI, USA | NCT01273181, Dec 201055 |
| 43 | MAGE-A3, EVDPIGHLY | HLA-A*01 | a3a TCR; yes; KD = 2.3 μM57 | Melanoma, high-risk or relapsed myeloma | 2 | III, IV | 2/2 deaths (cardiovascular toxicity to titin peptide: ESDPIVAQY in heart); Terminated | UPenn, Adaptimmune, USA | Dec 2011 (see refs. 56,57) |
| 44 | MAGE-A3 | HLA-A*01 | MAGE-A3 TCR; not specified | Breast, cervical, renal, bladder cancers; melanoma | 3 | I, II | Terminated | NCI, USA | NCT02153905, Jul 2014 |
| 45 | MAGE-A3:248–258, QHFVQENYLEY | HLA-DP0401 | MAGE-A3-DP4 TCR; no89 | Cervical, renal, urothelial, breast cancers; melanoma | 107 (est.) | I, II | Recruiting | NCI, USA | NCT02111850, Feb 2014 |
| 46 | MAGE-A3 and/or MAGE-A6 | HLA-DPB1*04:01 | MAGE-A3/A6 TCR (KITE-718); not specified | Solid tumors | 75 (est.) | I | Recruiting | Kite (Gilead), USA | NCT03139370, May 201790 |
| 47 | MAGE-A4:143–151, NYKRCFPVI | HLA-A*24:02 | MAGE-A4 TCR (TBI-1201); no91 | Solid cancers | 12 (est.) | I | Persistence of TCR-transduced T cells in 50% of patients (5/10); Recruiting | Mie University, Japan | UMIN00000239, NCT02096614, Apr 201492 |
| 48 | MAGE-A4:230–239, GVYDGREHTV | HLA-A*02 | MAGE-A4c1032 TCR; yes; not specified | Urinary bladder, head and neck, ovarian, esophageal, gastric cancers; SCS, NSCLC, MRCLS, melanoma | 42 (est.) | I | Recruiting | Adaptimmune, USA, Canada | NCT03132922, May 2017 |
| 49 | MAGE A10:254–262, GLYDGMEHL | HLA-A*02:01 and/or HLA-A*02:06 | MAGEA10c796; yes; KD = 370 nM93 | Advanced NSCLC | 28 (est.) | I | Recruiting | Adaptimmune, USA, Canada, Spain, LTK | NCT02592577, Nov 201585 |
| 50 | MAGE-A10 | HLA-A*02:01 and/or HLA-A*02:06 | MAGEA10c796; yes; KD = 370 nM93 | Urothelial carcinoma, bladder urothelial carcinoma, head and neck cancer; melanoma | 22 (est.) | I | Recruiting | Adaptimmune, USA, Canada, Spain | NCT02989064, Oct 201694 |
| 51 | MAGE-A4:230–239 GVYDGREHTV, MAGE-A10:254–262, GLYDGMEHL | HLA-A*02, HLA-A*02:01, HLA-A*02:06 | MAGE-A4c1032; yes; not specified; MAGEA10c796; yes; KD = 370 nM93 | Solid and hematological malignancies | 300 (est.) | — | Enrolling by invitation | Adaptimmune, USA, Canada | NCT03391791, Feb 2018 (long-term follow-up of subjects exposed to genetically engineered TCRs) |
| 52 | WT1: 126–134 RMFPNAPYL | HLA-A*02:01 | Cys1 WT1 TCR; no95 | AML, CML | 7 | I, II | No results posted | Cell Medica Ltd., UK | NCT01621724, April 2012 |
| 53 | WT1: 126–134 RMFPNAPYL | HLA-A*02:01 | WT1 TCRc4; no11 | High-risk AML, MDS, CML | 45 | I, II | Active, not recruiting, no results posted | Fred Hutch, USA | NCT01640301, Jul 2012 |
| 54 | WT1:126–134 RMFPNAPYL | HLA-A*02:01 | WT1 TCRc4 (JTCR016: Celgene); no11 | Stage III–IV NSCLC or mesothelioma | 20 (est.) | I, II | Active, not recruiting, no results posted | Fred Hutch, USA | NCT02408016, May 2015 |
| 55 | WT1 | HLA-A*02:01 | WT1 TCR (CMD-602); not specified | MDS, AML | 3 | I, II | No results posted | Cell Medica Ltd., Belgium, Germany, UK | NCT02550535, Sep 2015 |
| 56 | WT1:126–134 RMFPNAPYL | HLA-A*02:01 | WT1 TCRc4; no11 | AML | 9 | I, II | Active, not recruiting | Fred Hutch, USA | NCT02770820, Nov 2017 |
| 57 | Tyrosinase:368–376, 370D:YMDGTMSQV, 370N:YMNGTMSQV | HLA-A*02:01 | 1383I TCR; no; KD = 10 μM96,97 | Melanoma | 14 | I | 33% tumor shrinkage (1/3); 66% vitiligo (2/3) | Loyola University, USA | NCT01586403, July 201297 |
| 58 | Tyrosinase 368–376 370D:YMDGTMSQV, 370N:YMNGTMSQV | HLA-A*02:01 | 1383I TCR; no; KD = 10 μM96,97 | Melanoma | 18 (est.) | I | Recruiting | NCI, USA | NCT02870244, Feb 2015 |
| 59 | E6:29–38 TIHDIILECV | HLA-A*02:01 | HPV-16 E6 TCR; no98 | HPV-associated cancers | 12 | I, II | 1 CR; 1 PR | NCI, USA | NCT02280811, Oct 201499 |
| 60 | E6:29–38 TIHDIILECV |
HLA-A*02:01 | HPV-16 E6 TCR; no98 | High-grade squamous intraepithelial lesion | 200 (est.) | I | Recruiting | NCI, USA | NCT03197025, Jan 2018 |
| 61 | E7:11–19 epitope of HPV E7 protein | HLA-A*02:01 | E7 TCR; not specified100 | HPV-associated cancers | 180 (est.) | I, II | Recruiting | NCI, USA | NCT02858310, Jan 2017 |
| 62 | HBV antigen | Not specified | HBV antigen-specific TCR; not specified | HCC | 10 (est.) | I | Recruiting | Lion TCR Pte. Ltd., China | NCT02686372, Dec 2015 |
| 63 | HERV-E–derived antigen: ATWLGSKTWK | HLA-A* 11:01 | HERV-E TCR; not specified | Metastatic ccRCC | 24 (est.) | I | Recruiting | NHLBI, USA | NCT03354390, July 2018 |
| 64 | Human thyroglobulin (hTG) | HLA-A*02:01 | hTG mouse TCR; not specified | Metastatic thyroid cancer | 0 | I, II | Withdrawn | NCI, USA | NCT02390739, Mar 2015 |
| 65 | PRAME | HLA-A*02:01 | PRAME TCR (BPX-701); not specified101 | AML, MDS, uveal melanoma | 116 (est.) | I, II | Recruiting | Bellicum Pharmaceuticals, USA | NCT02743611, Apr 2017 |
| 66 | PRAME | HLA-A2*02:01 | MDG1011; not specified | High-risk myeloid and lymphoid neoplasms | 92 (est.) | I, II | Recruiting | Medigene AG, Germany | NCT03503968, Mar 2018 |
| 67 | AFP:158–166 FMNKFIYEI |
HLA-A*02:01 or HLA-A*02:642 | AFPc332 TCR; yes; KD = 10.6 μM102 | HCC | 24 (est.) | I | Recruiting | Adaptimmune, USA, Spain, UK | NCT03132792, May 2017 |
| 68 | KRAS G12V: (V) VVGAVGVGK, NRAS G12V, HRAS G12V | HLA-A*11:01 | KRAS G12V mouse TCR; no103 | Pancreatic, gastric, gastrointestinal, colon, rectal cancers | 110 (est.) | I, II | Recruiting | NCI, USA | NCT03190941, Sep 2017 |
| 69 | G12D variant of mutated RAS | HLA-A*11:01 | KRAS G12D mouse TCR; no103 | Gastrointestinal, pancreatic, gastric, colon, rectal cancers | 70 (est.) | I, II | Recruiting | NCI, USA | NCT03745326, Apr 2019 |
| 70 | Not specified | HLA-A*02:01 | IMA201; no | Solid tumors; HNSCC, NSCLC | 16 (est.) | I | Recruiting | Immatics US, Inc., USA | NCT03247309, Sep 2017 |
| 71 | Not specified | Not specified | IMA202; no | Solid tumors, including NSCLC and HCC | 16 (est.) | I | Recruiting | Immatics US, Inc., USA | NCT03441100, Apr 2019 |
| 72 | Not specified | Not specified | IMA203; no | Refractory/recurrent solid tumors | 16 (est.) | I | Recruiting | Immatics US, Inc., USA | NCT03686124, Mar 2019 |
| 73 | HA-1: VLHDDLLEA | HLA-A*02:01 | HA-1 TCR; no104 | Relapsed or refractory acute Leukemia | 24 (est.) | I | Recruiting | Fred Hutch, USA | NCT03326921, Feb 2018 |
| 74 | TGFβII | HLA-A*02 | Not specified; no | CRC | 5 (est.) | I, II | Recruiting | Oslo University Hospital, Norway | NCT03431311, Mar 2018 |
a
Previous or combination treatments are not listed.
b
AFP: Alpha-fetoprotein; CEA: carcinoembryonic antigen; HA-1: minor histocompatibility (H) antigen; HBV: hepatitis B virus; HPV: human papilloma virus; HERV-E–derived antigen: human endogenous retrovirus–derived antigen; MART-1: melanoma antigen recognized by T cells 1; NY-ESO-1: New York esophageal squamous cell carcinoma 1 [LAGE-1: cancer testis antigen homologous to NY-ESO-1 containing 157–165 peptide (SLLMWITQC)]; PRAME: preferentially expressed antigen in melanoma; TGFβII: transforming growth factor beta receptor type II; TRAIL/DR4: TNF-related apoptosis–inducing ligand bound to its receptor DR4; WT1: Wilms’ tumor antigen
c
AML: acute myeloid leukemia; ccRCC: clear cell renal cell carcinoma; CML: chronic myeloid leukemia; CRC: colorectal cancer; HCC: hepatocellular cancer; HNSCC: head and neck squamous cell carcinoma; MDS: myelodysplastic syndrome; MRCLS: myxoid/round cell liposarcoma; NSCLC: non-small-cell lung cancer; SCS: synovial cell sarcoma.
d
est.: estimated patient enrollment
e
CR: complete regression; nCR: near complete response; OR: objective regression; PR: partial response; VGPR: very good partial response
f
Fred Hutch: Fred Hutchinson Cancer Research Center; GSK: GlaxoSmithKline; JCCC (UCLA): Jonsson Comprehensive Cancer Center at the University of California, Los Angeles; MSD: Merck Sharp and Dohme Corp.; NCI: National Cancer Institute; NHLBI: National Heart, Lung, and Blood Institute; UPenn: University of Pennsylvania