Anish Thomas, MBBS, M.D.

Our primary hypothesis is that a rational use of DNA damage response inhibitors can enhance replicative stress and augment efficacy of currently available therapies including chemotherapies and immunotherapies. The secondary hypothesis is that tumor targeted chemotherapy delivery could improve the tolerability of DNA damage response inhibitor-combinations. We now have 5 ongoing trials addressing these hypotheses. Our first trial, a phase I trial of an ATR kinase inhibitor and topotecan recently completed enrolment and we are now enrolling patients on phase II. Other ongoing trials involve combinations of PARP inhibitors with tumor targeted chemotherapy or immunotherapy.

The following trials are recruiting small cell cancer patients:

1. A Phase II Trial of Topotecan plus VX970, an ATR Kinase Inhibitor (open also for extra-pulmonary small cell cancers)
2. A phase II Trial of anti-PDL1 antibody durvalumab plus olaparib (SCLC cohort)
3. A Phase I/II Trial of CRLX101, a Nanoparticle Camptothecin with Olaparib in Patients with Relapsed/Refractory Small Cell Lung, Bladder and Prostate Cancers

The following trials are recruiting solid tumor patients who have previously been treated with chemotherapy:

1. Phase I Study of a Combination of MM-398 and Veliparib in solid tumors
2. A Phase I/II Trial of CRLX101, a Nanoparticle Camptothecin with Olaparib in Patients with Relapsed/Refractory Small Cell Lung, Bladder and Prostate Cancers
3. The first-in-human phase I trial of PEN-866, PEN-866 in Patients With Advanced Solid Malignancies

Selected Recent Publications

1. Thomas A, Pommier Y. Small cell lung cancer: time to revisit the DNA damaging chemotherapy strategy. Science Translational Medicine 2016; 8:346fs12. PMID: 27384345
2. Thomas A, Redon C, Sciuto L, Padiernos E, Jiuping Ji, Lee M-J, Lee S, Zhang Y, Tran L, Yutzy W, Rajan A, Guha U, Chen H, Hassan R, Alewine C, Bates S, Kinders R, Steinberg S, Doroshow J, Aladjem M, Trepel J, Pommier Y. Phase I Study of ATR inhibitor M6620 in Combination with Topotecan in Patients with Advanced Solid tumors (in print Journal of Clinical Oncology).
3. Thomas A, Rajan A, Berman A, Tomita Y, Brzezniak C, Lee M-J, Lee S, Ling A, Spittler AJ, Carter CA, Guha U, Wang Y, Szabo E, Meltzer P, Steinberg SM, Trepel JB, Loehrer PJ, Giaccone G. Sunitinib in patients with chemotherapy refractory thymoma and thymic carcinoma: an open label phase II trial. Lancet Oncology. 2015; 16:177-86. PMID: 25592632.
4. Lopez-Chavez A, Thomas A (co-first author), Rajan A, Raffeld M, Morrow B, Kelly R,  Carter CA, Guha U, Killian K, Lau CL, Abdullaev Z, Xi L, Pack S, Meltzer PS, Corless CL, Sandler A, Beadling C, Warrick A, Liewehr DJ, Steinberg SM, Berman A,  Doyle A, Szabo E, Wang Y, Giaccone G. Molecular Profiling and Targeted Therapy for Advanced Thoracic Malignancies: a biomarker derived multi-arm, multi-histology phase II “basket” trial. Journal of Clinical Oncology. 2015 Feb 9. PMID: 25667274.
5. Enewold L, Thomas A. Real-World Patterns of EGFR Testing and Treatment with Erlotinib for Non-Small Cell Lung Cancer in the United States. PLoS One. 2016 Jun 13;11(6):e0156728. PMID: 27294665.
6. Thomas A, Liu SV, Subramaniam DS, Giaccone G. Refining the treatment of NSCLC according to histological and molecular subtypes. Nature Reviews Clinical Oncology. 2015 May 12. PMID: 25963091.
7. Thomas A, Chen Y, Steinberg S, Luo J, Giaccone G, Pastan I, Miettinen M, Hassan R. The prognostic role of mesothelin expression and its association with KRAS mutation in advanced lung adenocarcinoma. Oncotarget 2015;6:11694-703. PMID: 26028668.
8. Thomas A, Rajan A, Szabo E, Tomita Y, Carter CA, Scepura B, Lopez-Chavez A, Lee MJ, Redon CE, Frosch A, Peer CJ, Chen Y, Piekarz RL, Steinberg SM, Trepel JB, Figg W, Schrump DS, Giaccone G. A Phase I/II Trial of Belinostat in Combination with Cisplatin, Doxorubicin and Cyclophosphamide in Thymic Epithelial Tumors: A Clinical and Translational Study. Clinical Cancer Research. 2014; 20:5392-402. PMID: 25189481.