Table 1 Overview of PD-L1 and PD-1 inhibitors currently in development
Compound | Lead company | Antibody type | Affinity/K 2 | Selected tumour types assessed | Biomarker status |
|---|---|---|---|---|---|
Anti-PD-L1 | |||||
Atezolizumab (MPDL3280A) | Roche | Engineered IgG1 (no ADCC) | 0.4 nM | NSCLC: ORR: 21 %; 24-week PFS rate: 42 % [9] Median OS: 11.4 months (vs 9.5 with docetaxel) [10] | PD-L1 tested with SP142 mAb clone, with an automated system, and evaluated on both tumoral and immune-infiltrate cells, with a cut-off of ≥5 % and ≥10 % Biomarker status still experimental |
Durvalumab (MEDI4736) | AstraZeneca | Modified IgG1 (no ADCC) | NA | NSCLC: 12-week DCR: 41 %; ORR: 16 % [8] HNSCC: ORR: 12 % (25 % in PD-L1+ patients); 24-week DCR: 16 % (25 % in PD-L1+ patients) [43] Currently being assessed in first-line recurrent or metastatic HNSCC in combination with tremelimumab [44]. Also being assessed as monotherapy or in combination with tremelimumab in bladder, gastric, pancreatic, HCC and blood cancers. | PD-L1 tested with SP263 mAb clone, with an automated system, on tumoral cells, with a cut-off of ≥25 % Biomarker status still experimental |
BMS-936559 | Bristol-Myers Squibb | IgG4 (humanised) | NA | Being assessed in NSCLC, melanoma, and renal-cell cancer | PD-L1 tested with 28–8 mAb clone, with an automated system, on tumoral cells, with a cut-off of ≥5 % Biomarker status still experimental |
Anti-PD-1 | |||||
Nivolumab | Bristol-Myers Squibb | IgG4 | 2.6 nM | Approved in previously-treated advanced squamous or non-squamous NSCLC and RCC, metastatic melanoma, and HL that has relapsed or progressed after HSCT and post-transplantation brentuximab vedotin. Platinum-resistant ovarian cancer: ORR: 23 %; DCR: 54 % [25]. Advanced HCC: CR: 2/39 (5 %); PR 7/39 (18 %); 6-month OS: 72 % [32] Heavily pretreated RR-HL: ORR: 87 %; CR: 22 %. Mmedian DOR and median PFS not yet reached at median follow up of 101 weeks [53]. RR-DLBCL: ORR: 36 %; median overall DOR of 22 weeks [62]. RR-FCL: ORR: 40 %. At a median follow up of 91 weeks, the median DOR for responding patients was not yet reached [62]. | PD-L1 tested with 28–8 mAb clone, with an automated system, on tumoral cells, with a cut-off of ≥5 % Biomarker status: No testing required |
Pembrolizumab | Merck & Co | IgG4 (humanised) | 29 pM | Approved in previously-treated advanced squamous or non-squamous NSCLC and metastatic melanoma. Ovarian cancer: ORR: 11.5 %, 23.1 % of patients had evidence of tumor reduction; DCR: 34.6 % [27]. Esophageal cancer: ORR : 23 % (n = 5); best response was SD in 18 % (n = 4) and PD in 59 % (n = 13) [30]. Advanced gastric cancer: ORR: 22 % (95 % CI: 10–39) by central review and 33 % (95 % CI: 19–50) by investigator review. Median time to response was 8 weeks (range 7–16); median DOR: 24 weeks; 6-month PFS: 24 % and 6-month OS: 69 % [31]. HNSCC: ORR (confirmed and unconfirmed): 18.2 % (95 % CI: 11.1–27.2) with 18 partial responses and 31 with SD [39}. Recurrent/metastatic nasopharyngeal carcinoma: CR: 1/27; PR: 6/27; SD 14/27; The best ORR (confirmed and unconfirmed): 25.9 % (95 % CI, 11.1–46.3) [42]. RR-HL: ORR: 65 %; CR: 16 %; median PFS at 24 weeks: 69 % with a median DOR ≥24 weeks in 71 % of patients who achieved complete or partial response [54, 55]. | PD-L1 tested with 22C3 mAb clone, with an automated system, on tumoral cells, with a cut-off of ≥1 % and ≥50 % (strong positive). Biomarker status testing required (US) |
AMP-224 | GlaxoSmithKline | PD-L2 IgG1 Fc fusion | NA | Being assessed in metastatic colorectal cancer in combination with stereotactic body radiation therapy. | |
Othera | |||||
Pidilizumab | Medivation | IgG1 (humanised) | NA | Relapsed/refractory DLBCL: CR:34 %; ORR: 51 % in patients with measurable disease after transplant. In the whole cohort of patients, 16-month PFS from first treatment: 72 %; OS >80 % [60] Relapsed/refractory FCL in combination with rituximab: ORR: 66 %; CR: 52 %;. Median PFS for all patients:18.8 months, and not reached, at time of analysis, for the 19 patients with CR/PR | NR |