SUPPLEMENTARY INFORMATIONIn format provided by Gazdaret al. (doi:10.1038/nrc.2017.87)

Target / Agent/drug / Trial Status / References
Immune Therapies
CTLA4
PD1
PD-L1
Fucosyl-GM1
Various / Ipilumumab
Tremilumumab / Phase III
Phase II / 1
1
Nivolumab
Pembrolizumab / Phase III
Phase III / 1
2
Atezolizumab
Durvalumab / Phase II
Phase II / 3
1
BMS-986012 / Phase I / 4
Chimeric antigen receptor (CAR) Tcells / Preclinical / 5, 6
Antibody drug conjugates
DLL3
Somatostatin receptor / Rova T
Rhenium Re188–peptide P2045 / Phase III
Phase II / 7,8
9
DNA repair Inhibitors
PARP / Velaparib / Phase III / 10,1112
Olaparib / Phase III
Rucaparib / Phase II / 13
Talazoparib / Phase II / 14
WEE1 / AZD1775 / Phase II / 15
CHK1 / Prexaserib / Phase I / 16
ATR inhibitors / AZD6737 / Phase I / 17
ATM inhibitors / AZD0156 / Phase I
Stem Cell Inhibitors
Hedgehog
DLL4 / Erismodigib (LDE225)
Vismodigib (GDC044) / Phase II
Phase II / 18,19
Demicizumab
MEDI0639 / Phase II
Phase / 20
21
PIK3/mTOR Inhibitors
Everolimus / Phase II / 22
Temsirolimus / Phase II / 23
RET Inhibitors / Ponatinib / Preclinical / 24
Aurora kinase Inhibitors
Aurora A
Aurora B
Pan Aurora / Alisertib
Barasertib
PHA680632 / Phase II
Phase I
Preclinical / 25
26
25
Apoptosis
BCL2 / ABT263 (Navitoclax) / Phase II / 27
FGFR Inhibitors / Ponatinib
Lucitinib / Phase II
Phase II / 28
JAK Inhibitors
JAK2
JAK3 / AZD1480
Tofactinib / Phase I
Phase I / 29
30
Bromodomain inhibitors / JQ1 / Preclinical / 31
EZH2 inhibitors / GSK126
CPI1205 / Preclinical / 32
LSD1 Inhibitor / INCB059872 / Phase I / 33

Supplementary information 1 (table). Current clinical trials for targeted therapies in SCLC.

For a comprehensive list of currently available clinical trials in small cell lung cancer and for information about trials mentioned in the Table but not referenced, please see:

References

1Antonia, S. et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol17, 299-308, doi:10.1016/S1470-2045(15)00544-6 (2016).

2Ott PA, F. M., Hiret S, et al: & 7502., A. A. M. A. Pembrolizumab (MK-3475) in patients with extensive-stage small cell lung cancer: Preliminary safety and efficacy results from KEYNOTE-028. ASCO Meeting Abstract 7502 (2015).

3Horn, L. et al. PS01.57: IMpower133: a Phase I/III Study of 1L Atezolizumab with Carboplatin and Etoposide in Patients with Extensive-Stage SCLC: Topic: Medical Oncology. J Thorac Oncol11, S305-S306, doi:10.1016/j.jtho.2016.09.092 (2016).

4Krug, L. M. et al. Vaccination of small cell lung cancer patients with polysialic acid or N-propionylated polysialic acid conjugated to keyhole limpet hemocyanin. Clin Cancer Res10, 916-923 (2004).

5Levine, B. L. Performance-enhancing drugs: design and production of redirected chimeric antigen receptor (CAR) T cells. Cancer Gene Ther22, 79-84, doi:10.1038/cgt.2015.5 (2015).

6Rosenberg, S. A. & Restifo, N. P. Adoptive cell transfer as personalized immunotherapy for human cancer. Science348, 62-68, doi:10.1126/science.aaa4967 (2015).

7Saunders, L. R. et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci Transl Med7, 302ra136, doi:10.1126/scitranslmed.aac9459 (2015).

8Rudin, C. M. et al. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol18, 42-51, doi:10.1016/S1470-2045(16)30565-4 (2017).

9Edelman, M. J. et al. Targeted radiopharmaceutical therapy for advanced lung cancer: phase I trial of rhenium Re188 P2045, a somatostatin analog. J Thorac Oncol4, 1550-1554, doi:10.1097/JTO.0b013e3181bf1070 (2009).

10Owonikoko, T. et al. PS01.58: A Phase 3 Trial of Nivolumab, Nivolumab Plus Ipilimumab, or Placebo Maintenance for Extensive-Stage SCLC After First-Line Chemotherapy: Topic: Medical Oncology. J Thorac Oncol11, S306-S307, doi:10.1016/j.jtho.2016.09.093 (2016).

11Owonikoko, T. K. et al. A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E2511). Lung Cancer89, 66-70, doi:10.1016/j.lungcan.2015.04.015 (2015).

12Ramalingam, S. S. et al. Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non-Small Cell Lung Cancer. Clin Cancer Res, doi:10.1158/1078-0432.CCR-15-3069 (2016).

13Wilson, R. H. et al. A phase I study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumours. Br J Cancer, doi:10.1038/bjc.2017.36 (2017).

14Lok, B. H. et al. PARP Inhibitor Activity Correlates with SLFN11 Expression and Demonstrates Synergy with Temozolomide in Small Cell Lung Cancer. Clin Cancer Res23, 523-535, doi:10.1158/1078-0432.CCR-16-1040 (2017).

15Do, K. et al. Phase I Study of Single-Agent AZD1775 (MK-1775), a Wee1 Kinase Inhibitor, in Patients With Refractory Solid Tumors. J Clin Oncol33, 3409-3415, doi:10.1200/JCO.2014.60.4009 (2015).

16Sen, T. et al. CHK1 inhibition in small cell lung cancer produces single-agent activity in biomarker-defined disease subsets and combination activity with cisplatin or olaparib. Cancer Res, doi:10.1158/0008-5472.CAN-16-3409 (2017).

17Vendetti, F. P. et al. The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo. Oncotarget6, 44289-44305, doi:10.18632/oncotarget.6247 (2015).

18Kaur, G. et al. Bromodomain and hedgehog pathway targets in small cell lung cancer. Cancer Lett371, 225-239, doi:10.1016/j.canlet.2015.12.001 (2016).

19Pietanza, M. C. et al. A phase I trial of the Hedgehog inhibitor, sonidegib (LDE225), in combination with etoposide and cisplatin for the initial treatment of extensive stage small cell lung cancer. Lung Cancer99, 23-30, doi:10.1016/j.lungcan.2016.04.014 (2016).

20Smith, D. C. et al. A phase I dose escalation and expansion study of the anticancer stem cell agent demcizumab (anti-DLL4) in patients with previously treated solid tumors. Clin Cancer Res20, 6295-6303, doi:10.1158/1078-0432.CCR-14-1373 (2014).

21Jenkins, D. W. et al. MEDI0639: a novel therapeutic antibody targeting Dll4 modulates endothelial cell function and angiogenesis in vivo. Mol Cancer Ther11, 1650-1660, doi:10.1158/1535-7163.MCT-11-1027 (2012).

22Tarhini, A. et al. Phase II study of everolimus (RAD001) in previously treated small cell lung cancer. Clin Cancer Res16, 5900-5907, doi:10.1158/1078-0432.CCR-10-0802 (2010).

23Pandya, K. J. et al. A randomized, phase II trial of two dose levels of temsirolimus (CCI-779) in patients with extensive-stage small-cell lung cancer who have responding or stable disease after induction chemotherapy: a trial of the Eastern Cooperative Oncology Group (E1500). J Thorac Oncol2, 1036-1041, doi:10.1097/JTO.0b013e318155a439 (2007).

24Dabir, S. et al. RET mutation and expression in small-cell lung cancer. J Thorac Oncol9, 1316-1323, doi:10.1097/JTO.0000000000000234 (2014).

25Sos, M. L. et al. A framework for identification of actionable cancer genome dependencies in small cell lung cancer. Proc Natl Acad Sci U S A109, 17034-17039, doi:10.1073/pnas.1207310109 (2012).

26Helfrich, B. A. et al. Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo. Mol Cancer Ther15, 2314-2322, doi:10.1158/1535-7163.MCT-16-0298 (2016).

27Faber, A. C. et al. Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer. Proc Natl Acad Sci U S A112, E1288-1296, doi:10.1073/pnas.1411848112 (2015).

28Soria, J. C. et al. Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors. Ann Oncol25, 2244-2251, doi:10.1093/annonc/mdu390 (2014).

29Lee, J. H. et al. The Janus kinases inhibitor AZD1480 attenuates growth of small cell lung cancers in vitro and in vivo. Clin Cancer Res19, 6777-6786, doi:10.1158/1078-0432.CCR-13-1110 (2013).

30Curtis, J. R. et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis75, 831-841, doi:10.1136/annrheumdis-2014-205847 (2016).

31Lenhart, R. et al. Sensitivity of Small Cell Lung Cancer to BET Inhibition Is Mediated by Regulation of ASCL1 Gene Expression. Mol Cancer Ther14, 2167-2174, doi:10.1158/1535-7163.MCT-15-0037 (2015).

32Poirier, J. T. et al. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2. Oncogene, doi:10.1038/onc.2015.38 (2015).

33Mohammad, H. P. & Kruger, R. G. Antitumor activity of LSD1 inhibitors in lung cancer. Mol Cell Oncol3, e1117700, doi:10.1080/23723556.2015.1117700 (2016).

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