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Table 1 Overview of PD-L1 and PD-1 inhibitors currently in development

From: What have we learned from immunotherapy? Report from the 3rd and 4th meetings of the Campania Society of Oncology Immunotherapy (SCITO)

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
  1. ADCC antibody-dependent cell-mediated cytotoxicity, CR complete response, DCR disease control rate, DLBCL diffuse large B cell lymphoma, DOR duration of response, FCL follicular lymphoma, HCC hepatocellular carcinoma, HL Hodgkin’s lymphoma, HNSCC head and neck squamous cell carcinoma, HSCT hematopoietic stem cell transplantation, mAb monoclonal antibody, NA not available, NSCLC non-small cell lung cancer, ORR overall response rate, OS overall survival, PD progressive disease, PFS progression-free survival, PR partial response, RCC renal cell carcinoma, R/R relapsed/refractory, SD stable disease
  2. aPidilizumab was initially believed to have been an anti-PD-1 agent; however, it has recently been stated by Medivation that this is not the case although its exact mechanism of action has not been revealed