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Target molecule | Drug name | Phase | Status/NCT number | Disease | Number of patients | Study design | Response | Survival | Treatment-related adverse events (≧Gr3) | Reference |
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CTLA-4 | Ipilimumab |
III | Completed (NCT00094653) | Melanoma | 676 | Endpoint: safety/efficacy Ipi + gp100 versus Ipi versus gp100 | Ipi + gp100: ORR 5.7%; SD 14.4% | Ipi + gp100 versus gp100: 10.1 versus 6.4 mos | Ipi + gp100: drug-related 17.4%; irAEs 10.2%; diarrhea 4.5%; fatigue 5.0%; dyspnea 3.7%; anemia 2.9%; endocrine abnl. 11%; AST↑ 0.5%; ALT↑ 0.3% | [5] |
III | Completed (NCT00324155) | Melanoma | 502 | Endpoint: efficacy Ipi + DTIC versus PBO + DITC | Ipi + DTIC: ORR 15.2%; SD 18.0% | Ipi + DTIC versus PBO + DTIC: 11.2 versus 9.1 mos | Ipi + DTIC: immune-related 41.7%; pruritus 2.0%; rash 1.2%; diarrhea 4.0%; colitis 6.1%; AST↑ 17.4%; ALT↑ 20.7% | [6] |
Tremelimumab | III | Completed (NCT00257205) | Melanoma | 655 | Endpoint: efficacy treme. versus chemo. | ORR 10.7% | Treme. versus chemo.: 12.6 versus 10.7 mos (NS) | 52%; diarrhea/colitis 18%; fatigue 6%; rash 2%; pruritus 1%; dyspnea 3%; hypothalamus and pituitary disorders 1%; hepatitis 1% | [7] |
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PD-1 | Nivolumab (BMS-936558/ONO-4538) |
I | Ongoing (not recruiting) (NCT00730639) | Melanoma | 107 | Endpoint: safety/efficacy 5 dosing regimens | ORR 30.8%; median duration of response 104 wks; SD (≧24 wks) 6.5% | OS 16.8 mos; PFS 3.7 mos | 22.4%; fatigue 1.9%; diarrhea 1.9%; abdominal pain 1.9%; lymphopenia 2.8% | [8] |
I | Ongoing (not recruiting) (NCT01176461) | Melanoma | 90 | Endpoint: safety/efficacy 3 dosing regimens | ORR 25%; SD (≧24 wks) 21% | PFS (at 24 wks) 46% | 5.6%; rash 2.2%; interstitial pneumonitis 2.2% | [9] |
III | Ongoing (not recruiting) (NCT 01721772) | Melanoma | 370 | Endpoint: efficacy Nivo. versus ICC | ORR 32% versus 11% | NA | 9% versus 31% | [10] |
III | Completed (NCT01721772) | Melanoma | 418 | Endpoint: efficacy Nivo. versus dacarbazine | ORR 40.0% versus 13.9% | OS (at 1 yr) 72.9% versus 42.1%, median PFS 5.1 versus 2.2 mo | 11.7% versus 17.6%; fatigue 0.5%; diarrhea 1.0%; rash 0.5%; vomiting 0.5% | [11] |
Pidilizumab (CT-011) | II | Completed (NCT01435369) | Melanoma | 103 | Endpoint: safety/efficacy 2 dosing regimens | ORR 5.9% | OS (at 1 yr): 64.5% | NA | [12] |
Pembrolizumab (MK-3475) | I | Ongoing (not recruiting) (NCT01295827) | Melanoma | 135 | Endpoint: safety/efficacy 3 dosing regimens | ORR 38% by RECIST and 37% by irRC | Median PFS >7 mos | 13%; hypothyroidism 1%; diarrhea 1%; fatigue 1%; AST↑ 1%; renal failure 1%; rash 2%; pruritus 1% | [13] |
I | Ongoing (not recruiting) (NCT01295827) | Untreated NSCLC | 57 | Endpoint: safety/efficacy 3 dosing regimens | ORR 26% by RECIST and 47% by irRC | Median OS NR; OS at 1 yr 80%; median PFS 45.6%; PFS at 24 wks 70% | CK↑ 2%; pericardial effusion 2%; pneumonitis 2%; acute kidney injury 2% | [14] |
I | Ongoing (not recruiting) (NCT01848834) | Head and neck cancer | 60 | Endpoint: safety/efficacy single arm | ORR 19.6% in total, 20.0% in HPV+, and 19.4% in HPV−; | NA | Gr3–5 16.7%; Rash 3.3% | [15] |
I | Ongoing (not recruiting) (NCT01848834) | Gastric cancer | 39 | Endpoint: safety/efficacy single arm | ORR 30.2% by RECIST | NA | 7.7%; hypoxia 2.6%; peripheral neuropathy 2.6%; pneumonia 2.6% | [16] |
|
PD-L1 | BMS-936559 | I | Ongoing (not recruiting) (NCT00729664) | Melanoma | 52 | Endpoint: safety 4 dose levels | ORR 17%; SD (≧24 wks) 27% | PFS (at 24 wks) 42% | 9%; fatigue 1%; infusion reaction 1%; lymphopenia 1% |
[17] |
NSCLC | 49 | ORR 10%; SD (≧24 wks) 12% | PFS (at 24 wks) 31% |
Ovarian cancer | 17 | ORR 6%; SD (≧24 wks) 18% | PFS (at 24 wks) 22% |
Renal cell carcinoma | 17 | ORR 12%; SD (≧24 wks) 41% | PFS (at 24 wks) 53% |
MPDL3280A | I | Recruiting (NCT01375842) | Urothelial bladder cancer | 68 | Endpoint: safety/efficacy/ biomarker single arm | ORR: PD-L1 + 43% (at 6 wks) and 52% (at 12 wks); PD-L1 − 11% (at 6 wks); | NA | 4%; no irAE | [18] |
MEDI4736 | I | Recruiting (NCT01693562) | Advanced solid tumors | 26 (as of Jan 2014) | Endpoint: safety/efficacy single arm | PR 15.4%; disease control rate (≧12 wks) 46% | NA | Any Gr 34%; Gr3/4 0%; no DLT; no MTD | [19] |
MSB0019718C | I | Recruiting (NCT01772004) | Refractory malignancies | 27 (as of Jan 2014) | Endpoint: safety single arm | NA | NA | Treatment discontinuation 52.2% (8.7% for AEs); drug-related AEs 11.1%; DLT 3.7% (CPK↑, myositis, and myocarditis) | [20] |
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