Copyright
©The Author(s) 2016.
World J Gastroenterol. Nov 21, 2016; 22(43): 9457-9476
Published online Nov 21, 2016. doi: 10.3748/wjg.v22.i43.9457
Published online Nov 21, 2016. doi: 10.3748/wjg.v22.i43.9457
Table 1 Clinical trials on cytotoxic T lymphocyte antigen 4
Target molecule | Drug name | Study phase | Study design | Status | Condition | Intervention | Cohort | Estimated enrollment | Dose | End point | Study Arm | Adverse event | Response | Survival | Ref. |
CTLA-4 | Ipilimumab (BMS-734016/MDX-010) | 1 | NA | Active | PC | Palliative | Locally advanced | 28 | DE | Safety (MTD, DLT) | Ipilimumab, Gemcitabine | NA | NA | NA | NCT01473940 |
Not recruiting | Metastatic | Efficacy (RR, PFS, OS) | |||||||||||||
2 | Randomized | Recruiting | PC | Palliative | Metastatic | 92 | 3 mg/kg | Safety (AE) | Ipilimumab, GVAX (Arm A) | NA | NA | NA | NCT01896869 | ||
Efficacy (OS, PFS, ORR, DoR) | FOLFIRINOX (Arm B) | ||||||||||||||
Tremelimumab (CP-675/CP-675,206) | 2 | NA | Recruiting | PC, BlC, BC | Palliative | Metastatic | 77 | NA | Safety | Tremelimumab (Arm A) | NA | NA | NA | NCT02527434 | |
Efficacy (ORR, DoR, DCR, PFS, OS, BoR) | Durvalumab (Arm B) | ||||||||||||||
Tremelimumab, Durvalumab (Arm C) | |||||||||||||||
2 | Randomized | Recruiting | PC | Palliative | Metastatic | 130 | NA | Safety | Durvalumab (Arm A) | NA | NA | NA | NCT02558894 | ||
Efficacy (ORR, DoR, DCR, PFS) | Durvalimab, Tremelimumab (Arm B) | ||||||||||||||
PK | |||||||||||||||
Antidrug Antibody Presence | |||||||||||||||
1 | Randomized | Recruiting | PC, NSCLC, HNSCC | Palliative | Locally advanced | 108 | NA | Safety (AE, DLT) | Durvalumab, Mogamulizumab (Arm A) | NA | NA | NA | NCT02301130 | ||
Metastatic | Tremelimumab, Mogamulizumab (Arm B) | ||||||||||||||
1 | Non-randomized | Recruiting | PC, NSCLC, BC, MM | Palliative | Metastatic | 30 | 1 mg/kg | Safety (AE) | Durvalumab, Tremelimumab, Radiotherapy | NA | NA | NA | NCT02639026 | ||
Efficacy |
Table 2 Clinical trials on programmed cell death 1
Target molecule | Drug name | Study phase | Study design | Status | Condition | Intervention | Cohort | Estimated enrollment | Dose | End point | Study Arm | Adverse event | Response | Survival | Ref. |
PD-1 | Nivolumab (BMS-936558/MDX-1106/ONO-4538) | 1|2 | Randomized | Recruiting | PC | Neoadjuvant | Resectable | 50 | 3 mg/kg | Safety | Cy/GVAX ( Arm A) | NA | NA | NA | NCT02451982 |
Adjuvant | Efficacy (IRAEs, OS, DFS) | Cy/GVAX, Nivolumab (Arm B) | |||||||||||||
Median-[IL17A] in Vaccine-induced Lymphoid Aggregates | |||||||||||||||
1|2 | Non-randomized | Recruiting | PC, NSCLC, RCC, CrC, EC, UC | Palliative | Metastatic | 49 | NA | Safety | Nivolumab, Temsirolimus (Arm A) | NA | NA | NA | NCT02423954 | ||
Efficacy | Nivolumab, Irinotecan (Arm B) | ||||||||||||||
RD | Nivolumab, Irinotecan, capecitabine (Arm C) | ||||||||||||||
1 | Non-randomized | Recruiting | PC, NSCLC, CrC, MM, HNSCC, GBM | Palliative | Locally advanced | 270 | 3 mg/kg | Safety (AE) | Phase 1a: | NA | NA | NA | NCT02526017 | ||
Efficacy (OS; mOS, oyOS, DOR, PFS, ORR; CR, PR) | FPA008 (Arm A) | ||||||||||||||
Tolerability | FPA008, Nivolumab (Arm B) | ||||||||||||||
RD | Phase 1b: | ||||||||||||||
PK | MTD/RD FPA008, Nivolumab | ||||||||||||||
Immunogenicity | |||||||||||||||
PDA biomarkers | |||||||||||||||
1 | Non-randomized | Recruiting | PC, OC, BC, CrC, RCC, MM, PrC, NSCLC | Palliative | Locally advanced | 300 | 3 mg/kg | Safety | DE AM0010 (Arm A) | NA | NA | NA | NCT02009449 | ||
Metastatic | Tolerability | DE AM0010, Paclitaxel/Docetaxel, Carboplatin/Cisplatin (Arm B) | |||||||||||||
PK | DE AM0010, FOLFOX, (Arm C) | ||||||||||||||
DE AM0010, gemcitabine/nab-paclitaxel (Arm D) | |||||||||||||||
DE AM0010, Capecitabine (Arm E) | |||||||||||||||
DE AM0010, Paclitaxel (Arm F) | |||||||||||||||
DE AM0010, Pazopanib (Arm G) | |||||||||||||||
DE AM0010, Pembrolizumab (Arm H) | |||||||||||||||
DE AM0010, Nivolumab (Arm I) | |||||||||||||||
DE AM0010, Gemcitabine/carboplatin (Arm J) | |||||||||||||||
Pembrolizumab (MK-3475/SCH 900475) | 2 | NA | Not recruiting | PC | Palliative | Locally advanced | 54 | 200 mg | Safety (IRAEs) | Cy/GVAX, Pembrolizumab, SBRT | NA | NA | NA | NCT02648282 | |
Efficacy (DMFS, OS, LPFS) | |||||||||||||||
2 | Randomized | Active | PC | Palliative | Locally advanced | 76 | NA | Safety (TEAE) | ACP-196 (Arm A) | NA | NA | NA | NCT02362048 | ||
Not recruiting | Metastatic | Efficacy | ACP-196, Pembrolizumab (Arm B) | ||||||||||||
1|2 | Randomized | Recruiting | PC | Neoadjuvant | Resectable | 56 | 200 mg | Safety (DLT) | Pembrolizumab, Capecitabine, Radiotherapy | NA | NA | NA | NCT02305186 | ||
Borderline resectable | Efficacy (DFS, OS, RR) | ||||||||||||||
[TILs] | |||||||||||||||
1|2 | Non-randomized | Recruiting | PC, SCLC, OC, BC, Sarcoma | Palliative | Metastatic | 90 | 2 mg/kg | Safety (AE) | Pembrolizumab, Gemcitabine (Arm A) | NA | NA | NA | NCT02331251 | ||
Efficacy (ORR, OS, PFS) | Pembrolizumab, Gemcitabine, Docetaxel (Arm B) | ||||||||||||||
RD | Pembrolizumab, Gemcitabine, Nab-paclitaxel (Arm C) | ||||||||||||||
Pembrolizumab, Gemcitabine, Vinorelbine (Arm D) | |||||||||||||||
Pembrolizumab, Irinotecan (Arm E) | |||||||||||||||
Pembrolizumab, Liposomal, Doxorubicin (Arm F) | |||||||||||||||
1 | Non-randomized | Recruiting | PC | Palliative | Locally advanced | 50 | 200 mg | Safety | Pembrolizumab, Defactinib, Gemcitabine | NA | NA | NA | NCT02546531 | ||
Metastatic | Efficacy | ||||||||||||||
1 | NA | Active | PC, RC, NSCLC, BlC, ASN, RCC, CC, HCC, BC, MM, HNSCC, Sarcoma | Palliative | Metastatic | 12 | NA | Safety | Pembrolizumab, p53MVA | NA | NA | NA | NCT02432963 | ||
Not recruiting | Efficacy (Clinical Response) | ||||||||||||||
Tolerability | |||||||||||||||
2 | Non-randomized | Suspended | PC, ChC, GeC, CrC, HCC | Palliative | Metastatic | 290 | 2 mg/kg | Safety | Pebrolizumab, Young TIL, Aldesleukin, Cyclophosphamide, Fludarabine | NA | NA | NA | NCT01174121 | ||
Efficacy | |||||||||||||||
1 | NA | Recruiting | PC | Palliative | Locally advanced | 9 | 2 mg/kg | Safety (DLT) | Pembrolizumab, Reolysin, Gemcitabine/Irinotecan/Leucovorin with 5-FU | NA | NA | NA | NCT02620423 | ||
Metastatic | Efficacy (ORR, PFS, OS) | ||||||||||||||
1|2 | NA | Recruiting | PC, ChC, GeC, CrC | Palliative | Locally advanced | 128 | DE | Safety | Pembrolizumab, mFOLFOX6, Celecoxib | NA | NA | NA | NCT02268825 | ||
Metastatic | Efficacy (RR, PFS, OS) | ||||||||||||||
1 | Non-randomized | Recruiting | PC, OC, BC, CrC, RCC, MM, PrC, NSCLC | Palliative | Locally advanced | 300 | 3 mg/kg | Safety | DE AM0010 (Arm A) | NA | NA | NA | NCT02009449 | ||
Metastatic | Tolerability | DE AM0010, Paclitaxel/Docetaxel, Carboplatin/Cisplatin (Arm B) | |||||||||||||
PK | DE AM0010, FOLFOX, (Arm C) | ||||||||||||||
DE AM0010, gemcitabine/nab-paclitaxel (Arm D) | |||||||||||||||
DE AM0010, Capecitabine (Arm E) | |||||||||||||||
DE AM0010, Paclitaxel (Arm F) | |||||||||||||||
DE AM0010, Pazopanib (Arm G) | |||||||||||||||
DE AM0010, Pembrolizumab (Arm H) | |||||||||||||||
DE AM0010, Nivolumab (Arm I) | |||||||||||||||
DE AM0010, Gemcitabine/carboplatin (Arm J) | |||||||||||||||
Pidilizumab (CT-011) | 2 | NA | Suspended | PC | Adjuvant | Resectable | 29 | 3 mg/kg | Safety | Pidilizumab, Gemcitabine | NA | NA | NA | NCT01313416 | |
Efficacy (Median DFS) | |||||||||||||||
1 | Non-randomized | Withdrawn | PC, OC, BC, CC, Sarcoma | Palliative | NA | 0 | DE | Safety | Pidilizumab, p53 Vaccine | NA | NA | NA | NCT01386502 | ||
Efficacy |
Table 3 Clinical trials on programmed cell death ligand 1
Target molecule | Drug name | Study phase | Study design | Status | Condition | Intervention | Cohort | Estimated enrollment | Dose | End point | Study Arm | Adverse event | Response | Survival | Ref. |
PD-L1 | Durvalumab (MEDI4736) | 2 | Non-randomized | Not recruiting | PC, GeC, OC, NSCLC, BC, RCC, CrC | Palliative | Metastatic | 136 | 750 mg > 30 kg, | Safety Efficacy (ORR, PFS, OS) | Durvalumab | NA | NA | NA | NCT02669914 |
10 mg/kg < 30 kg | |||||||||||||||
2 | NA | Recruiting | PC, BlC, BC | Palliative | Metastatic | 77 | NA | Safety | Tremelimumab (Arm A) | NA | NA | NA | NCT02527434 | ||
Efficacy (ORR, DoR, DCR, PFS, OS, BoR) | Durvalumab (Arm B) | ||||||||||||||
Tremelimumab, Durvalumab (Arm C) | |||||||||||||||
1 | Non-randomized | Recruiting | PC, HNSCC, MM, CrC, BC, CEC | Palliative | Locally advanced | 40 | NA | Safety (AE) | Durvalumab, Selumetinib | NA | NA | NA | NCT02586987 | ||
Metastatic | Efficacy (ORR, BoR, DoR) | ||||||||||||||
Tolerability | |||||||||||||||
PK | |||||||||||||||
2 | Randomized | Recruiting | PC | Palliative | Metastatic | 130 | NA | Safety | Durvalumab (Arm A) | NA | NA | NA | NCT02558894 | ||
Efficacy (ORR, DoR, DCR, PFS) | Durvalimab, Tremelimumab (Arm B) | ||||||||||||||
PK | |||||||||||||||
Antidrug Antibody Presence | |||||||||||||||
1|2 | Non-randomized | Recruiting | PC | Palliative | Metastatic | 26 | NA | Safety (DLT) | Durvalumab , nab-Paclitaxel, Gemcitabine (Arm A) | NA | NA | NA | NCT02583477 | ||
Efficacy (ORR, DoR, DCR, PFS) | Durvalumab, AZD5069 (Arm B) | ||||||||||||||
PK | |||||||||||||||
1 | Randomized | Recruiting | PC, NSCLC, HNSCC | Palliative | Locally advanced | 108 | NA | Safety (AE, DLT) | Durvalumab, Mogamulizumab (Arm A) | NA | NA | NA | NCT02301130 | ||
Metastatic | Tremelimumab, Mogamulizumab (Arm B) | ||||||||||||||
1 | Non-randomized | Recruiting | PC, NSCLC, BC, MM | Palliative | Metastatic | 30 | 1 mg/kg | Safety (AE) | Durvalumab, Tremelimumab, Radiotherapy | NA | NA | NA | NCT02639026 | ||
Efficacy |
Table 4 Immune checkpoint inhibitors based on American Society of Clinical Oncology's meeting abstracts
Target molecule | Drug name | Study phase | Study design | Status | Condition | Intervention | Cohort | Estimated enrollment | Dose | End point | Study Arm | Adverse event | Response | Survival | Ref. |
CTLA-4 | Tremelimumab | 1 | Non-randomized | Recruiting | PC | Palliative | Metastatic | 60 | NA | Safety | Durvalumab, SBRT (Arm A) | NA | NA | NA | Duffy et al[28] |
(CP-675/CP-675,206) | Efficacy (ORR, PFS) | Tremelimumab, SBRT (Arm B) | |||||||||||||
Tolerability | Durvalumab, Tremelimumab, SBRT (Arm C) | ||||||||||||||
PK | |||||||||||||||
PD-1 | Nivolumab | 2 | Randomized | Recruiting | PC | Palliative | Metastatic | 94 | 3 mg/kg | Safety (TRT) | Cy/GVAX/Nivolumab, CRS-207/Nivolumab (Arm A) | NA | NA | NA | Le et al[25] |
(BMS-936558/MDX-1106/ONO-4538) | Efficacy (OS, PFS, RR) | Cy/GVAX, CRS-207 (Arm B) | |||||||||||||
1 | Randomized | Recruiting | PC, NSCLC, BC | Palliative | Locally advanced | 138 | 3 mg/kg | Safety (DLT, TEAEs) | Nivolumab, nab-Paclitaxel (Arm A) | NA | NA | NA | Firdaus et al[45] | ||
Metastatic | Efficacy (PFS, OS, DCR, ORR, DR) | Nivolumab, nab-Paclitaxel, Gemcitabine (Arm B) | |||||||||||||
Pembrolizumab | 1|2 | Non-randomized | Recruiting | PC, GeC, OC, NSCLC, BC, BlC, MM, HNSCC, | Palliative | Locally advanced | 400 | 200 mg | Safety | Part A: Pembrolizumab, DE Pexidartinib (PLX3397) | NA | NA | NA | Wainberg et al[50] | |
(MK-3475/SCH 900475) | Metastatic | Efficacy (ORR; CR, PR) | Part B: RD Pexidartinib (PLX3397), Pembrolizumab | ||||||||||||
PD-L1 | Durvalumab (MEDI4736) | 1 | Non-randomized | Recruiting | PC | Palliative | Metastatic | 60 | NA | Safety | Durvalumab, SBRT (Arm A) | NA | NA | NA | Duffy et al[31] |
Efficacy (ORR, PFS) | Tremelimumab, SBRT (Arm B) | ||||||||||||||
Tolerability | Durvalumab, Tremelimumab, SBRT (Arm C) | ||||||||||||||
PK | |||||||||||||||
1|2 | NA | Recruiting | PC, NSCLS, mBC | Palliative | Metastatic | 160 | NA | Safety (AE, DLT) | Part 1: Durvalumab, DLT Ibrutinib | NA | NA | NA | Borazanci et al[74] | ||
Efficacy | Part 2: Durvalumab, RD Ibrutinib | ||||||||||||||
Tolerability | |||||||||||||||
RD | |||||||||||||||
PK |
Table 5 Immune checkpoint inhibitors based on articles
Target molecule | Drug | Study phase | Study design | Condition | Intervention | Cohort | Enrollment | Dose | End point | Study Arm | Adverse event | Response | Survival | Ref. |
CTLA-4 | Ipilimumab | 2 | Non-randomized | PC | Palliative | Locally advanced | 27 | 3 mg/kg | Efficacy (ORR; CR, PR) | Ipilimumab | 11% Grade 3-4 irAEs (Colitis: 1, Encephalitis: 1, Hypophysitis: 1) | No RECIST-response | NA | Royal et al[23] |
(BMS-734016/MDX-010) | Metastatic | SD: delayed progression, RECIST-progressive disease (n:1) | ||||||||||||
1 | Randomized | PC | Palliative | Locally advanced | 30 | 10 mg/kg | Safety (AE) | Ipilimumab (Arm A) | 73%, 80% irAEs (Arm A, B) | SD: growth < 20% growth cut-off, 7w (n:1) , 22w (n:1) (Arm A) regression 17w (n:1), stabilization 59w (n:1), 71w (n:1) (Arm B) | mOS (95%CI:) IPI vs IPI, GVAX: 3.6 (2.5-9.2), 5.7 (4.3-14.7); | Le et al[24] | ||
Metastatic | Efficacy (OS, ORR) | Ipilimumab, GVAX (Arm B) | 20% Grade 3-4 irAEs (Colitis: 1, GBS: 1, Nephritis: 1) (Arm A), (Rash: 1, Colitis: 1, Pneumonitis: 1) (Arm B) | HR = 0.51, 95%CI: 0.23-1.08, P = 0.072. | ||||||||||
irAEs (p: 0.037) | yOS (95%CI:) IPI vs IPI, GVAX: 7% (1%-45%), 27% (11%-62%) | |||||||||||||
Tremelimumab (CP-675/CP-675,206) | 1 | Non-randomized | PC | Palliative | Metastatic | 34 | 15 mg/kg | Safety (AE, DLT, MTD) | Tremelimumab DE (C6, C10, C15), Gemcitabine | Grade 3-4 irAEs (Asthenia: 1, Nausea: 1, Diarrhea: 1, Anemi: 1, Pruritus: 1, Hypertransaminasemia: 1) (C 10), (Asthenia: 3, Nausea: 2, Diarrhea:1, Anemi: 1, Neutropenia: 2, Hypertransaminasemia: 1, Thrombocytopenia:2) (C 15) SAE:11 (Dehydration-diarrhea: 1, ACS: 1, PE: 1, Hyperbilirubinemia: 1, Hematemesis: 1) (C10) (AKI: 1, GIB: 1, Hyperbilirubinemia: 2) (C15) | PR: 8w (n:2) (10.5%: 2/19) | mOS (95%CI:) C6 (6 mg/kg Tremelimumab), C10 (10 mg/kg Tremelimumab), C15 (15 mg/kg Tremelimumab): 5.3 (1.2-14.6), 8.0 (2.3-16.9), 7.5 (6.0-9.5) | Aglietta et al[27] | |
Efficacy (OS, OR, PFS) | SD: > 10w [n:7 (n:2 completed study)] | |||||||||||||
PD-L1 | BMS-936559 | 1 | Non-randomized | PC, NSCLC, MM, CrC, OC, GeC, RRC, BC | Palliative | Locally advanced | 207 (14 PDA) | DE | Safety (AE, MTD, DLT) | BMS-936559 | NA | No objective PDA-response | NA | Brahmer et al[79] |
Metastatic | Efficacy (ORR) | |||||||||||||
PK |
- Citation: Johansson H, Andersson R, Bauden M, Hammes S, Holdenrieder S, Ansari D. Immune checkpoint therapy for pancreatic cancer. World J Gastroenterol 2016; 22(43): 9457-9476
- URL: https://www.wjgnet.com/1007-9327/full/v22/i43/9457.htm
- DOI: https://dx.doi.org/10.3748/wjg.v22.i43.9457