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Table 2 Summary of reported clinical efficacy of PD-1/PD-L1 inhibitors

From: Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy

Agent Clinical trials identifier Phase of clinical trial Sample size (no. Pt) Patient population Biomarker Regimen Tumor responses (ORR) Median PFS (months) OS (months; median unless otherwise specified) Reference: author (year)
Nivolumab NCT01642004 (CheckMate 017) Phase III 272 all: 135 nivolumab, 137 docetaxel Advanced squamous NSCLC with disease progression during or after first-line chemotherapy PD-L1-positive tumor cells Nivolumab 3 mg/kg IV every 2 weeks 20 % 3.5 9.2 Brahmer J (2015) [125]
Docetaxel 75 mg/m2 IV every 3 weeks 9 % 2.8 6
NCT01673867 (CheckMate 057) Phase III 582 all: 292 nivolumab, 290 Docetaxel Advanced non-squamous NSCLC after platinum-based doublet chemotherapy PD-L1-positive tumor cells Nivolumab 3 mg/kg IV every 2 weeks 19 % 2.3 12.2 Borghaei H (2015) [126]
Docetaxel 75 mg/m2 IV every 3 weeks 12 % 4.2 9.4
NCT01668784 (CheckMate 025) Phase III 821 all: 406 nivolumab, 397 Everolimus Advanced clear-cell renal-cell carcinoma with one or two regimens of anti-angiogenic therapy PD-L1-positive tumor cells Nivolumab 3 mg/kg IV every 2 weeks 25 % 4.6 25 Motzer RJ (2015) [127]
Everolimus 10 mg orally daily 5 % 4.4 19.6
NCT01721746 (CheckMate 037) Phase III 631 all: 272 nivolumab,133 investigators choice of chemo Unresectable or metastatic melanoma after ipilimumab or ipilimumab and BRAF inhibitor if BRAF positive PD-L1-positive tumor cells Nivolumab 3 mg/kg IV every 2 weeks 32 % 4.7 NA Weber JS (2015) [128]
Chemo: either dacarbazine 1000 mg/m2 IV every 3 weeks or carboplatin AUC = 6 plus paclitaxel 185 mg/m2 IV every 3 weeks 11 % 4.2 NA
NCT01927419 (CheckMate 069) Phase III 142 all: 95 nivolumab + ipilimumab, 47 ipilimumab Unresectable or metastatic melanoma treatment naïve with measurable disease Tissue available for PD-L1 biomarker analysis Nivolumab 1 mg/kg IV every 3 weeks × 4 doses plus ipilimumab 3 mg/kg IV every 3 weeks × 4 doses, then maintenance nivolumab 3 mg/kg IV every 2 weeks BRAF wild type: 61 %; BRAF mutation: 52 % BRAF wild type: NR; BRAF mutation: 8.5 NA Postow MA (2015) [4]
Same dose schedule with nivolumab placebo in both the combination and maintenance phase BRAF wild type: 11 %; BRAF mutation: 22 % BRAF wild type: 4.4; BRAF mutation: 2.7 NA
NCT01721772 (CheckMate 066) Phase III 418 all: 210 nivolumab, 208 dacarbazine Untreated metastatic melanoma without BRAF mutation Tissue available for PD-L1 biomarker analysis Nivolumab 3 mg/kg IV every 2 weeks plus placebo every 3 weeks 40 % 5.1 1-year OS: 72.9 % Robert C (2015) [129]
Dacarbazine 1000 mg/m2 IV every 3 weeks plus placebo every 2 weeks 13.9 % 2.2 1-year OS: 42.1 %
NCT01844505 (CheckMate 067) Phase III 945 all: 316 nivolumab, 314 combination, 315 ipilimumab Untreated, unresectable stage III or IV melanoma Tissue available for PD-L1 biomarker analysis Nivolumab 3 mg/kg IV every 2 weeks (plus ipilimumab placebo) 43.7 % 6.9 NA Larkin J (2015) [130]
Nivolumab 1 mg/kg IV every 3 weeks plus ipilimumab 3 mg/kg IV every 3 weeks × 4 doses; then maintenance nivolumab 3 mg/kg IV every 2 weeks 58 % 11.5
Ipilimumab 3 mg/kg IV every 3 weeks (plus nivolumab placebo) 19 % 2.9
NCT01721759 (CheckMate 063) Phase II single arm trial 117 Advanced NSCLC PD-L1-positive tumor cells Nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxic effects 14.5 % 1.9 8.2 Rizvi NA (2015) [131]
NCT00730639 Phase I with expansion cohorts 107 Advanced melanoma Unselected Nivolumab at 1, 3, or 10 mg/kg every 2 weeks for up to 96 weeks 31 % 3.7 16.8 Topalian SL (2014) [67]
Phase I with expansion cohorts 34 Previously treated advanced RCC Unselected Nivolumab at 1, 3, or 10 mg/kg every 2 weeks for up to 96 weeks 29 % 7.3 22.4 McDermott DF (2015) [132]
Phase II with expansion cohorts 129 Heavily pretreated advanced NSCLC Unselected Nivolumab at 1, 3, or 10 mg/kg every 2 weeks for up to 96 weeks 17 % 2.6 9.9 Gettinger SN (2015) [133]
Pembrolizumab NCT01866319 (KEYNOTE-006) Phase III 834 all: 279 pembrolizumab, 277 pembrolizumab, 278 ipilimumab Unresectable stage III or IV melanoma PD-L1-positive tumor cells Pembrolizumab 3 mg/kg IV every 2 weeks 33.7 % 5.5 NA Robert C (2015) [134]
Pembrolizumab 3 mg/kg IV every 3 weeks 32.9 % 4.1
Ipilimumab 3 mg/kg IV every 3 weeks 11.9 % 2.8
NCT01704287 (KEYNOTE-002) Phase II 540 all: 180 pembrolizumab, 181 pembrolizumab, 179 chemotherapy Ipilimumab-refractory melanoma Will be reported with the final overall survival analysis Arm A 2 mg/kg (n = 180) 21 % 5.4 NA Ribas A (2015) [135]
Arm B 10 mg/kg (n = 181) 25 % 5.8
Chemotherapy 4 % 3.6
NCT012958297 (KEYNOTE-001) Phase I 495 Advanced NSCLC PD-L1-positive tumor cells Pembrolizumab 2 or 10 mg/kg IV every 3 weeks or 10 mg/kg every 2 weeks over a 30-min period 19.4 % 3.7 12 Garon EB (2015) [5]
Phase I 655 Melanoma Unselected Pembrolizumab 2 mg/kg every 3 weeks (Q3W), 10 mg/kg Q3W, or 10 mg/kg Q2W until unacceptable toxicity, disease progression, or investigator decision 33 % 12-month PFS 35 % 23 Adil Daud (2015) [136]; Ribas A (2016) [137]
Phase I with expansion cohort 173 Advanced melanoma after at least 2 ipilimumab doses Unselected Pembrolizumab 2 mg/kg IV every 3 week or 10 mg/kg IV every 3 weeks 26 % 2 NA Robert C (2014) [138]
NCT01848834 (KEYNOTE-012) Phase IB 32 Metastatic triple-negative breast cancer PDL-1-positive tumor cells Pembrolizumab 10 mg/kg IV every 2 weeks 19 % 6-month PFS 23.3 % NA Nanda R (2014) [139]
NCT1905657 (KEYNOTE-010) Phase II/III 1034 all: 339 pembrolizumab, 343 pembrolizumab, 309 docetaxel Previously treated PD-L1-positive advanced NSCLC PDL-1-positive tumor cells Pembrolizumab 2 mg/kg, IV every 3 weeks 18 % 3.9 months 14.9 Herbst RS [2015] [140]
Pembrolizumab 10 mg/kg, IV every 3 weeks 18.5 % 4.0 month 17.3
Docetaxel, 75 mg/m2 every 3 weeks 9.3 % 4.0 month 8.2
NCT01953692 (KEYNOTE-013) Phase IB 15 Hodgkin lymphoma Unselected Pembrolizumab 10 mg/kg IV every 2 weeks up to 2 years 53 % NA NA Moskowitz C (2014) [141]
Atezolizumab (MPDL3280A) NCT01846416 Phase II 205 NSCLC PD-L1-positive tumor cells Atezolizumab 1200 mg IV every 3 weeks The highest ORR was seen in pts with PD-L1 TC3 or IC3 tumors NA NA Spigel DR (2015) [142]
NCT01903993 (POPLAR) Phase II 287 Previously treated NSCLC patients (pts) were stratified by PD-L1 IC status PD-L1-positive tumor cells Atezolizumab 1200 mg IV every 3 weeks 57 % 2.7 12.6 Spira AI (2015) [143]; Fehrenbacher L (2016)
Docetaxel 75 mg/m2 IV every 3 weeks 24 % 3.0 9.7
NCT01375842 Phase I 35 Metastatic melanoma PD-L1-positive tumor cells Atezolizumab IV every 3 weeks for up to 1 year 26 % 24-week PFS 35 % NA Omid Hamid (2013) [144]
Phase I 277 Multiple cancer types PD-L1-positive tumor cells Atezolizumab intravenously every 3 weeks doses >1 ml/kg 18 % 2.6 NA Herbst RS (2014) [145]
NCT01633970 Phase Ib 37 Untreated NSCLC PD-L1-positive tumor cells Atezolizumab 15 mg/kg IV every 3 weeks with standard chemo dosing for 4–6 cycles followed by MPDL3280A maintenance therapy until progression 67 % NA NA Stephen V (2015) [146]
Phase Ib 14 Arm A: refractory metastatic colorectal cancer; arm B: oxaliplatin-naive mCRC Not mentioned Arm A: MPDL3280A 20 mg/kg every 3 weeks and bevacizumab (bev) 15 mg/kg every 3 weeks 8 % (1/13) in arm A NA NA Bendell, J.C. (2015) [147]
Arm B: MPDL3280A 14 mg/kg every 2 weeks, bev 10 mg/kg every 2 weeks and mFOLFOX6 at standard doses 36 % (9/25) in Arm B NA NA
Phase Ib 12 Metastatic renal cell carcinoma Not selected Atezolizumab 15 mg/kg given alone on cycle 1 day 1 and concurrently with 20 mg/kg every 2 weeks thereafter 40 % NA NA Sznol M (2015) [148]
Durvalumab (MEDI4736) NCT01693562 Phase I/II 198 NSCLC Tissue available for PD-L1 biomarker analysis Durvalumab 10 mg/kg IV every 2 weeks until unacceptable toxicity, disease progression, or for up to 12 months 14 % (23 % in PD-L1+ tumors) NA NA Rizvi NA (2015) [149]
Phase I 13 NSCLC Tissue available for PD-L1 biomarker analysis Durvalumab 7 doses (1–25) across 6 cohorts (0.1–10 mg/kg every 2 weeks; 15 mg/kg every 3 weeks) NA NA NA Brahmer JR (2014) [150]
Multi-arm expansion study 62 A squamous cell carcinoma of the head and neck expansion cohort Tissue available for PD-L1 biomarker analysis Durvalumab IV every 2 weeks at 10 mg/kg for 12 months 12 % (25 % in PD-L1+ pts) NA NA Segal NH (2015) [151]
Phase I 26 Advanced solid tumors Durvalumab IV every 2 (q2w) or 3 weeks (q3w) in a 3 + 3 dose escalation with a 28-day (q2w) or 42-day (q3w) DLT window NA NA NA Lutzky J (2014) [152]
NCT02088112 Phase I 10 NSCLC Unselect Durvalumab cohort A received 3 mg/kg (starting dose) every 2 weeks plus gefitinib 250 mg QD NA NA NA Creelan BC (2015) [153]
NCT02000947 Phase Ib 118 (102 eligible) NSCLC Tissue available for PD-L1 biomarker analysis Durvalumab 10–20 mg/kg every 2 or 4 weeks plus tremelimumab 1 mg/kg (N = 56) 23 % (6/26): 22 % (2/9) in PD-L1+ versus 29 % (4/14) in PD-L1- NA NA Antonia SJ (2015) [154]; Updated in Antonia SJ (2016) [155]
Durvalumab 10–20 mg/kg every 2 weeks plus tremelimumab 3 mg/kg (N = 34) 20 % (5/25)
Durvalumab 15 mg/kg every 4 weeks plus tremelimumab 10 mg/kg (N = 9) 0 % (0/9)
  1. Abbreviations: DLT dose-limiting toxicity, q2w every 2 weeks, q3w every 3 weeks, q4w every 4 weeks, QD once daily, BRAF B-raf and v-raf murine sarcoma viral oncogene homologue B1, NA not available