1 Introduction
1.1 Company Agreements
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Mirati Therapeutics’ mocetinostat in NSCLC (agreement signed in August 2015) [6].
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Peregrine’s bavituximab in solid tumours, including NSCLC (August and October 2015) [7].
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Eli Lilly’s ramucirumab, galunisertib, LY2510924 or LY3022855 in solid tumours (August and October 2015) [8].
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Celgene’s anticancer drugs in haematological malignancies (April 2015) [9].
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Gilead’s idelalisib in haematological cancers/solid tumours, including diffuse large B-cell lymphoma and triple-negative breast cancer (first quarter of 2015) [10].
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Innate Pharma’s monalizumab in cancer (April 2015) [11].
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Pharmacyclics (a subsidiary of AbbVie) and Janssen Biotech’s ibrutinib in solid tumours and haematological malignancies (November 2014) [12].
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Immunocore’s IMC gp100 in melanoma (April 2015) [13].
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Advaxis’ axalimogene filolisbac in human papillomavirus (HPV)-associated cervical cancer and HNSCC (July 2014) [14].
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Kyowa Hakko Kirin’s mogamulizumab in solid tumours (July 2014) [15].
2 Scientific Summary
2.1 Pharmacodynamics
2.2 Pharmacokinetics
Alternative names | Anti-PD-L1 monoclonal antibody; Anti-PD-LI mAb; anti-programmed cell death 1 ligand 1 monoclonal antibody; Imfinzi; MEDI-4736 |
Class | Antineoplastics; monoclonal antibodies |
Mechanism of action | CD274 antigen inhibitors |
Route of administration | Intravenous |
Pharmacodynamics | Binds to PD-L1 with high affinity and selectivity, blocking its interaction with PD-1 and CD80 receptors; induces T-cell activation and proliferation; inhibits tumour growth in xenograft models. |
Pharmacokinetics | Dose-proportional pharmacokinetics at ≥3 mg/kg; mean terminal half-life 17 days; |
Most frequent adverse events | Fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral oedema and urinary tract infection |
ATC codes | |
WHO ATC code | B06A (other hematological agents); L01X-C28 (durvalumab) |
EphMRA ATC code | B6C (other haematological agents); L1G (monoclonal antibody antineoplastics); L1X9 (all other antineoplastics) |
Chemical name | Immunoglobulin G1-kappa, anti-(human programmed cell death 1 ligand 1 (B7 homolog 1, CD274)); human monoclonal antibody; γ1 heavy chain (1-451) [human VH (IGHV3-7*01 (99%)–IGHJ4*01) [8.8.14] (1–121)–IGHG1*03 (CH1 (122–219), hinge (220–234), CH2 L4 > F(238), L5 > E(239), P101 > S(335) (235-344), CH3 (345–451)) (122–451)] (224–215′)-disulfide with κ light chain (1′–215′) [human V-KAPPA (IGKV3-20*01 (97%)–IGKJ1*01) [7.3.9] (1′–108′)–IGKC*01(109′–215′)] dimer (230–230″:233–233″)-bisdisulfide |
2.3 Therapeutic Trials
2.3.1 Urothelial Carcinoma
2.3.2 Non-small Cell Lung Cancer
2.3.3 Head and Neck Squamous Cell Carcinoma
2.3.4 Other Cancers
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Durvalumab monotherapy in an open-label phase II trial (NCT02336165) in bevacizumab-naive patients with recurrent glioblastoma (estimated 6-month progression-free survival 20.0%; ORR 13.3%; stable disease rate 40.0%; n = 30) [27].
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Durvalumab monotherapy in a phase I trial (NCT01938612) in Japanese patients with advanced solid tumours [28].
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Durvalumab plus olaparib in a phase II trial (NCT02484404) in previously treated patients with metastatic castration-resistant prostate cancer (6-month progression-free survival 86.7%, 9-month progression-free survival 57.8%; n = 19) [29] and in a phase I (NCT02484404) trial in patients with ovarian cancer or triple-negative breast cancer without germline BRCA mutation [30].
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Durvalumab plus axalimogene filolisbac in a phase I/II trial (NCT02291055) in previously treated patients with recurrent/metastatic HPV-associated cervical cancer [31].
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Durvalumab plus darafenib plus trametinib in a phase I/II trial (NCT02027961) in patients with BRAF mutant or wild type metastatic or unresectable melanoma [32].
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Durvalumab plus tremelimumab in a phase I trial (NCT02141347) in Japanese patients with advanced solid tumours [33].
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Durvalumab plus MEDI0680 in a phase I trial (NCT02118337) in patients with advanced malignancies [18].
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Durvalumab plus AZD9150 (antisense oligonucleotide against STAT3) or AZD5069 (CXCR2 antagonist) in a phase Ib/II trial (NCT02499328) in patients with advanced malignancies [34].
Drug(s) | Indication | Phase | Status | Identifier |
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Durvalumab ± tremelimumab, SoC (1st line) | Stage IV urothelial carcinoma | III | Recruiting | NCT02516241; DANUBE |
Durvalumab, SoC (1st line) | Advanced NSCLC | III | Recruiting | NCT03003962; PEARL |
Durvalumab ± tremelimumab, SoC (1st line) | Advanced/metastatic NSCLC | III | Ongoing | NCT02453282; MYSTIC |
Durvalumab + tremelimumab, SoC (1st line) | Advanced/metastatic NSCLC | III | Recruiting | NCT02542293; NEPTUNE |
Durvalumab ± tremelimumab, SoC (3rd line) | Advanced/metastatic NSCLC | III | Ongoing | NCT02352948; ARCTIC |
Durvalumab + concurrent chemoradiation | Stage III unresectable NSCLC | III | Ongoing | NCT02125461; PACIFIC |
Durvalumab, placebo (adjuvant therapy) | Completely resected NSCLC | III | Recruiting | NCT02273375; ADJUVANTa
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Durvalumab, multiple comparators (biomarker-targeted 2nd line) | Stage IV squamous NSCLC | II/III | Recruiting | NCT02154490; Lung Master Protocola
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Durvalumab (3rd line) | Advanced/metastatic NSCLC | II | Ongoing | NCT02087423; ATLANTIC |
Durvalumab ± tremelimumab + chemotherapy | Advanced SCLC | III | Recruiting | NCT03043872; CASPIAN |
Durvalumab + tremelimumab, AZD1775 + carboplatin | Extensive stage SCLC | II | Recruiting | NCT02937818; BALTIC |
Durvalumab ± tremelimumab, SoC (1st line) | Recurrent/metastatic HNSCC | III | Ongoing | NCT02551159; KESTREL |
Durvalumab ± tremelimumab, SoC (2nd line) | Recurrent/metastatic HNSCC | III | Recruiting | NCT02369874; EAGLE |
Durvalumab | Recurrent/metastatic HNSCC | II | Ongoing | NCT02207530; HAWK |
Durvalumab, tremelimumab, durvalumab + tremelimumab | Recurrent/metastatic HNSCC | II | Ongoing | NCT02319044; CONDOR |
Durvalumab + tremelimumab, durvalumab, tremelimumab | Unresectable hepatocellular carcinoma | II | Recruiting | NCT02519348 |
Durvalumab + tremelimumab, durvalumab | Advanced solid tumours | III | Recruiting | NCT03084471; STRONG |
Durvalumab | HIV-1 plus solid tumours | II | Recruiting | NCT03094286 |
Durvalumab, tremelimumab, durvalumab + tremelimumab | Advanced solid tumours | II | Ongoing | NCT02527434 |
Durvalumab (≥2nd line) | Advanced solid tumours | I/II | Ongoing | NCT01693562; Study 1108 |