Background
Principles of cancer immunotherapy
Target | Drug | Class | Company | Clinical indication and ongoing evaluation (status; approval date; trial identifier; country) |
---|---|---|---|---|
CTLA-4 | Ipilimumab (Yervoy®, MDX-010, MDX-101) | Human IgG1/kappa | Bristol-Myers Squibb |
Metastatic melanoma (US FDA approved on March 25, 2011); metastatic NSCLC (phase I has been completed; NCT01165216; Japan; phase II reported, NCT00527735, USA; phase III ongoing, NCT01285609; USA; phase III ongoing NCT02279732; China) |
Tremelimumab (ticilimumab, CP-675206) | Human anti-CTLA-4 IgG2 mab | MedImmune/AstraZeneca |
Metastatic melanoma (phase I has been completed; NCT01103635; USA; phase II has been completed, NCT00471887, USA); advanced hepatocellular carcinoma (phase II has been completed; NCT01008358; Spain); Metastatic NSCLC (phase Ib has been reported, NCT02000947, USA; phase II has been reported, NCT02179671, USA; first line, phase III MYSTIC ongoing; NCT02453282; USA) | |
PD-1 | Nivolumab (Opdivo®, ONO-4538, MDX-1106, BMS-936558) | Human IgG4/kappa | Bristol-Myers Squibb; Ono Pharmaceuticals |
Metastatic melanoma (Japan approval on July 4, 2014; US FDA accelerated approval on December 22, 2014; US FDA approval of nivolumab in combination with ipilimumab for BRAF V600 wild-type tumor on September 30, 2015); Squamous NSCLC (US FDA approval on March 4, 2015; European Commission on July 20, 2015); expands to non-squamous NSCLC (US FDA approval on October 9, 2015); advanced (metastatic) renal cell carcinoma (US FDA approval on November 23, 2015); classical Hodgkin lymphoma that has relapsed or progressed after autologous hematopoietic stem cell transplantation and post-transplantation brentuximab vedotin (US FDA approval on May 17, 2016) |
Pembrolizumab (Keytruda®, lambrolizumab, MK-3475) | Humanized IgG4 | Merck & Co. |
Metastatic melanoma (USA accelerated approval on September 4, 2014 for patients with disease progression after ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor; US FDA expanded to initial treatment on December 18, 2015); metastatic NSCLC whose tumors express PD-L1 as determined by an FDA-approved test and who have disease progression on or after platinum-containing chemotherapy (US FDA approval on October 2, 2015) | |
Pidilizumab (CT-011) | Humanized IgG1 | CureTech Ltd |
Diffuse large-B cell lymphoma (phase II has been completed; NCT00532259; USA); metastatic melanoma (phase II has been completed; NCT01435369; USA) | |
AMP-514 (MEDI0680) | Humanized IgG4 | MedImmune |
Advanced malignancies (phase II is currently recruiting participants; NCT02013804; USA) | |
AUNP-12 | Peptide antagonist | Aurigene, Pierre Fabre |
Cancer (preclinical phase, Aurigene granted Pierre Fabre worldwide rights to develop AUNP12 for cancer indications; announced on February 11, 2014; India) | |
PD-L1 | BMS936559 (MDX-1105) | Human IgG4 | Bristol-Myers Squibb |
Advanced or recurrent solid tumors (phase II has been completed; NCT00729664; USA) |
Atezolizumab (Tecentriq™, MPDL3280A, RG7446) | Human IgG1 | Roche & Genentech |
Metastatic bladder cancer (phase III, US FDA granted breakthrough therapy designation on May 31, 2014; priority review on March 14, 2016; accelerated approval on May 18, 2016); metastatic NSCLC (phase III, US FDA grants breakthrough therapy designation on February 1, 2015) | |
Durvalumab (MEDI4736) | Humanized IgG1 | AstraZeneca |
Glioblastoma (phase II is currently recruiting participants; NCT02336165; USA); metastatic squamous cell carcinoma of the head and neck (phase II is currently recruiting participants; NCT02207530; USA); advanced or metastatic NSCLC (phase III is currently recruiting participants; NCT02352948; Global study); advanced colorectal cancer (phase II is currently recruiting participants; NCT02227667; USA); metastatic NSCLC (first line phase III MYSTIC is current recruiting participants; NCT02453282; USA; first line phase III ARCTIC is current recruiting participants; NCT02352948; Global); metastatic bladder cancer (US FDA granted breakthrough therapy designation for PD-L1-positive tumors in patients who progressed during or after one standard platinum-based regimen on February 17, 2016) | |
Avelumab (MSB0010718C) | Fully humanized IgG1 | Merck KGaA, EMD Serono, Pfizer |
Advanced solid tumors (phase I with consecutive parallel group expansion; currently recruiting participants in multiple tumor types and settings; NCT01772004; USA); metastatic NSCLC (phase III is currently recruiting participants after failure of a platinum-based doublet; NCT02395172; and first line versus platinum doublet; NCT02576574; USA) | |
PD-L2 | AMP-224 | PD-L2-IgG2a fusion protein | Amplimmune |
Advanced cancer (phase II has been completed; NCT01352884; USA) |
Biology and mechanisms of PD-1 and PD-L1 molecules
Clinical efficacy of PD-1/PD-L1 blockade therapies and PD-L1 expression
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 | |||
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 | ||
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) |
Biomarkers for PD-1/PD-L1 blockade therapies
Biospecimen | Method | Tissue/cell types | Pros | Cons | References and recommended reading |
---|---|---|---|---|---|
FFPE | IHC | Tumor cells or tumor infiltrating immune cells | Direct detection; accurately pinpoint cancer cells; highly sensitive; simplicity; low cost | Requirement of trained pathologists; inconsistency for criteria used to score tumors such as PD-L1-positive or negative | |
Multicolor IHC | Tumor cells or tumor infiltrating immune cells | Broad dynamic range; capability for multiplexing using different fluorescence channels; >10 protein targets are identified in the same sample; amenability for co-localization studies | Absence of rigorous quantitative tests; limitation in some biomarker-driven clinical trials; user must select combinations of dyes | Carvajal-Hausdorf DE (2014) [165] | |
T cell receptor deep sequencing | TILs | T cell count information; T cell clonality in tumor | Heterogeneous expression of TIL | Robbins HS (2013) [100] | |
Whole exome sequencing (WES) | Tumor cells | Characterization of tumor mutation load including nucleotide substitutions; structural rearrangements and copy number alterations; identification of the neoantigens and neoepitopes; affordable cost | Require high-performance deep sequencing, computational bioinformatics support; The pipelines are still at early developmental phase | Bouffet E (2016) [107]; Chen K-H (2016) [166] Hugo W (2016) [106] | |
Blood | ELISPOT assays (IFNγ and granzyme B) | T cells in PBMCs | Detection of tumor antigen-specific CD4+ and CD8+ T cell response with good assay sensitivity; Relatively well validated assay | A poor correlation with clinically relevant immune responses | |
Flow cytometry (tetramer, polyfunctional analysis) | T cells in PBMCs | Assessment of tumor antigen-specific CD4+ and CD8+ T cells response; measure multiple functions; detection of neoantigen-specific CD8 + PD-1+ T cells; minimally invasive | Merely in lab research, not as routine clinical monitoring yet | ||
Flow cytometry phenotype staining | Whole blood immune phenotype | Analyses of the frequency and proliferation of different subsets of immune cells; routine operation | Dedicated resource and staff to perform the analyses | ||
RNA-Seq (NGS) | T cells in PBMCs | Identification of genetic variants; a broader dynamic range; detection of more differentially expressed genes; fast and high efficiency | More expensive than microarray; more complex for analysis; bulk signature, not single cell signals; need more validation | Zhao S (2010) [171] | |
qPCR assay | T cells in PBMCs | High specificity; able to detect the reactivity of low-frequency T cells in the peripheral blood of metastatic cancer patients | Bulk signature, not single cell signals; need more validation | Kammula US (2008) [172] | |
Flow cytometry | CTCs | Qualitative analysis at the single cell level in a relatively short period of time; decrease the amount of blood needed; provide valuable information regarding the frequency, phenotype and/or the functionality of T cells | Expensive; need more validation | Zaritskaya L (2010) [83] | |
Cell sieve microfiltration assay and QUASR technique | CTCs | PD-L1 levels from CTCs or CAMLs serves as a surrogate for PD-L1 expression in tumor; as a marker for immunotherapy response | Limited in lab research; need more validation |
Current immune monitoring assays
IHC staining
Drug | Antibody (marker) | Rx line | Tumor type | Targeted cells | Tumor specimen | Cutoff point (%) | ORR % in IHC+ cases (95 % CI) | ORR % in IHC− cases (95 % CI) | Predictive role |
P value | References |
---|---|---|---|---|---|---|---|---|---|---|---|
Nivolumab | 28-8 rabbit (Dako) | 1 L | Melanoma | TCs | Archival FFPE or new biopsy | 5 | 58 (46,69) | 41 (35,48) | Yes | 0.001 | Larkin J (2015) [130] |
Nivolumab + ipilimumab | 72 (60,82) | 55 (48,62) | Yes | 0.001 | |||||||
Nivolumab | ≥2 L | 5 | 44 (30,58) | 20 (11,32) | Yes | NA | Weber JS (2015) [128] | ||||
Nivolumab + ipilimumab | 1 L | 5 | 58 (37,78) | 55 (42,69) | No | >0.05 | Postow MA (2015) [4] | ||||
Nivolumab | 1 L | 5 | 53 (41,64) | 33 (25,42) | No | >0.05 | Robert C (2015) [129] | ||||
≥2 L | NSCLC | TCs | Archival FFPE or new biopsy | 1 | 31 (23,40) | 9 (5,16) | Yes | 0.002 | |||
5 | 36 (26,46) | 10 (6,17) | Yes | 0.002 | |||||||
10 | 37 (27,48) | 11 (6,17) | Yes | 0.002 | |||||||
≥2 L | Archival FFPE | 1 | 17 (9,29) | 17 (8,29) | No | 0.9364 | Brahmer JR (2015) [125] | ||||
5 | 21 (10,37) | 15 (8,25) | No | 0.2908 | |||||||
10 | 19 (8,36) | 16 (9,26) | No | 0.6411 | |||||||
≥2 L | Archival FFPE | 1 | 20 (5,35) | 13 (2,28) | No | >0.05 | Rizvi NA (2015) [131] | ||||
5 | 24 (5,43) | 14 (3,25) | No | ||||||||
1 L | Archival FFPE | 5 | 31 (NA) | 10 (NA) | No | >0.05 | Gettinger SN (2015) [157] | ||||
Nivolumab + ipilimumab | 1 L | Archival FFPE | 5 | 19 (NA) | 14 (NA) | No | >0.05 | Antonia SJ (2014) [158] | |||
Nivolumab | 5H1 and anti-PD-1 monoclonal M3 | ≥2 L | Archival FFPE | 5 | 39 (34,44) | 6 (1,12) | Yes | 0.025 | Taube JM (2014) [113] | ||
Pembrolizumab | 22C3 mouse (Dako) | ≥1 L | NSCLC | TCs and ICs | New biopsy | 50 | 45 (33,57) | 17 (10,25) | Yes | 0.001 | Garon EB (2015) [5] |
1 L | New biopsy | 50 | 47 (23,72) | 19 (8,38) | Yes | NA | Rival NA (2015) [159] | ||||
Any | Archival FFPE | 1 | 25 (NA) | 13 (NA) | Yes | NA | Garon EB (2014) [160] | ||||
≥1 L | Archival FFPE | 50 | 30 (23,39) | 9.8 (NA) | Yes | NA | Herbst RS (2015) [140] | ||||
29 (22,37) | 10.7 (NA) | ||||||||||
1 L | Archival FFPE | 50 | 16 (NA) | 10 (NA) | Yes | NA | Garon EB (2014) [161] | ||||
Atezolizumab (MPDL3280A) | SP142 rabbit (Roche Ventana) | ≥2 L | NSCLC | TCs and ICs | Archival FFPE and new biopsy | 50 | 45 (23,68) | 14 (6,25) | Yes | NA | Leora H (2015) [162] |
≥2 L | NSCLC | 1+ | 31 (25,37) | 20 (14,26) | Yes | 0.015 | Herbst RS (2014) [145] | ||||
Solid Tumor | 1+ | 29 (27,31) | 13 (10,16) | Yes | 0.007 | ||||||
≥2 L | NSCLC | 2+ | 18 (NA) | 8 (NA) | Yes | NA | Spira AI (2015) [143] | ||||
Durvalumab (MEDI-4736) | SP263 rabbit (Roche Ventana) | ≥2 L | NSCLC | TCs | Archival FFPE and new biopsy | 25 | 39 (NA) | 5 (NA) | Yes | NA | Segal NH (2014) [163] |
33 (13,59) | 30 (16,47) | No for combo | NA | Antonia SJ (2016) [155]; | |||||||
22 (3, 60) | 29 (8, 58) | No for monotherapy | NA |