Table 2.
CAR-T clinical trials for solid tumors with published results
| Antigen | Identifier | Patients n Age (median; range) |
Dosage | Persistence | Outcome n (median; range) in month | Adverse events | Ref |
|---|---|---|---|---|---|---|---|
| FR-a | NCT00019136 | 14 (33–60) | 0.3–5 × 1010 T cells | Up to > 1 year | NE: 14 | Grade 3/4 toxicities including hypotension and dyspnea as well as less frequently fatigue, leukopenia, rigors, sinus tachycardia, and diarrhea, in some patients receiving IL-2 | [35] |
| CAIX | DDHK9729/P00.0040C | 12 62,5 (46–74) |
0.2–2.1 × 109 (split dose over 2 × 5 days) |
Up to 4 weeks | NE: 12 | Transient liver enzyme disturbances (grade 3/4) observed in 4 patients, caused by attack of CAR-T cells to CAIX-expressing bile duct epithelial cells | [36, 115–117] |
| L1-CAM | NCT00006480 | 6 9,5 (7–16) |
1 × 108–1.1 × 109/m2 (split dose; 2–3 times of infusions 14 days apart) |
Up to 42 days | CR: 1 (1,5) SD: 1 (1) PD: 4 |
Grade 3 lymphopenia, neutropenia, low hemoglobin and bacteremia caused by 108/m2 CAR-T cells infusion grade 3 pneumonitis for one patient, which was associated with 109/m2 CAR-T cells infusion |
[38] |
| MSLN | NCT01355965 | 2 78 (75–81) |
3 infusions with 0.1–1 × 109 cells or 8 infusions with 3 × 108 cells and 2 infusions with 2 × 108 cells | Transient (mRNA CAR) | PR: 1 (6) SD: 1 |
Anaphylactic reaction in one patient, leading to grade 4 cardiac arrest, respiratory failure, disseminated intravenous coagulation, and CRS grade 4 jejunal obstruction, grade 3 abdominal pain, and grade 2 lymphcytosis for another patient |
[39, 40] |
| NCT01897415 | NA | 3 times per week for 3 weeks | Transient (mRNA CAR) | SD: 2 | Grade > 3 toxicities included abdominal pain (1) and back pain (1) | [41] | |
| HER2 | NCT00924287 | 1 39 |
1 × 1010 total | NA | Death: 1 | Respiratory distress and dramatic pulmonary infiltrate on chest X-ray were observed soon after CAR-T cell administration. Severe hypotension, bradycardia, gastrointestinal bleeding, resulting in a cardiac arrest. The patient died 5 days after the CAR-T infusion. |
[119] |
| NCT01109095 | 17 49 (11–79) |
1 × 106-1 × 108/m2 | Up to 12 weeks | SD: 7 PD: 8 PR: 1 |
NA | [43] | |
| NCT00902044 | 19 16 (7–29) |
1 × 104-1 × 108/m2 (up to 9 infusions) |
Up to 18 month | SD: 4 (0,5; 0,5–14) PD: 13 NE: 2 |
Fever observed in 1 patient | [28] | |
| NCT01935843 | 11 61 (50–75) |
2.1 × 106/kg (range 1.4–3.8 × 106/kg), 1 to 2 cycles | Up to 80 days | PR: 1 (4.5) SD: 5 (4.8; 1.5–8.3) |
Mild-to-moderate fatigue, nausea, vomiting, myalgia, arthralgia, and lymphopenia, Except one grade 3 acute febrile syndrome and one abnormal elevation of transaminase | [42] | |
| EGFR | NCT01869166 | 11 58 (40–66) |
4 × 105–2.54 × 107/kg | Up to 37 weeks | PR: 2 (3; 2–3,5) SD: 5 (5,5; 2–8+) PD: 4 |
Mild skin toxicity, nausea, vomiting, dyspnea, and hypotension; one patient suffered from a transient grade 3/4 increase in serum lipase | [44] |
| EGFR and CD133 | NCT01869166 NCT02541370 | 1 52 |
EGFR: 2.2 × 106/kg first cycle, 2.1 × 106/kg second cycle, CD133: 1.22 × 106/kg |
NA | EGDR: PR (8.5) CD133: PR (2.5) |
EGFR: mild chills, fever, fatigue, vomiting and muscle soreness, and a 9-day duration of delayed lower fever CD133: an intermittent upper abdominal dull pain, chills, fever, and rapidly deteriorative grade 3 systemic subcutaneous hemorrhages and congestive rashes together with serum cytokine release |
[45] |
| IL-13Ra2 | NCT00730613 | 3 57 (36–57) |
1.6 × 108 for first cycle + 3 × 108 for second to fourth cycle (split dose in each cycle; 3 infusions 2 days apart) |
Up to 14 weeks | PR: 2 (12; 10–14) PD: 1 |
Grade 3 headache in two patients receiving 108 CAR-T cells infusion grade 3 neurologic adverse events observed in 1 patient |
[30] |
| NCT02208362 | 1 50 |
Intracavitary infusions (cycles 1 through 6) and intraventricular infusions (cycles 7 through 16), maximum dose: 10 × 106 cells | Detectable at 149 days after enrollment | CR:7.5 | No CAR-T cell infusion related toxic effects of grade 3 or higher were observed | [33] | |
| CEA | NCT01373047 | 7 53,5 (51–66) |
1 × 108–1 × 1010 cells (single hepatic artery infusion) |
NA | SD: 1 (23) PD: 5 NE: 1 |
Grade 3 fever and tachycardia (1 patient), associated to high-dose IL-2 administration. grade 1/2 transient elevations of alkaline phosphatase, total bilirubin and aspartate aminotransferase levels observed in all patients |
[31] |
| GD2 | NCT00085930 | 19 7 (3–29) |
1.2 × 107-1 × 108/m2 (single infusion) | Up to 192 weeks for ATC and 96 weeks for CTLs | CR: 11 PR: 1 SD: 1 PD: 6 |
Mild to moderate local pain at the site of tumor necrosis in two patients | [46, 124] |
| MUC1 | NCT02587689 | 1 | 5 × 105 cells per lesion | NA | PR: 1 | Mild headache, muscle pain, nasal congestion, and abdominal bloating discomfort, and a transient CRS was experienced | [29] |
| PSMA | BB-IND 12084 | 5 61 (51–75) |
1 × 109–1 × 1010 cells | Up to 4 week | PR: 3 NE: 2 |
Grade 3/4 hematologic toxicities including neutropenia, neutropenic fever, and thrombocytopenia in all the patients; anemia, hypocalcemia, hypophosphatemia, and appendicitis in one patient. Grade 1/2 skin rash, fatigue, intermittent low-grade fevers, and muscle pain in some patients |
[48] |
| VEGFR-II | NCT01218867 | 23 | 1 × 106–3 × 1010 cells | NA | PR: 1 SD: 1 PD: 21 |
Grade 3/4 toxicity include nausea, vomiting, hypoxia, and elevated levels of aspartate transaminase, alanine transaminase, and bilirubin | Results available at www.ClinicalTrials.gov |
The patient characteristics, CAR-T treatment dosage, CAR-T cell persistence, clinical outcomes, and adverse events of CAR-T clinical trials with published results are listed
Abbreviations: NE no response, CR clinical response, PR partial response, SD stable disease, PD progress disease, NA not available