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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

2124 - Phase I study: Safety and tolerability of Varlitinib (VAR) in combination with Oxaliplatin and Capecitabine (COX) or Oxaliplatin and 5-FU (FOL) in advanced solid tumours

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Topics

Cytotoxic Therapy;  Clinical Research

Tumour Site

Presenters

Amanda Seet

Citation

Annals of Oncology (2018) 29 (suppl_8): viii133-viii148. 10.1093/annonc/mdy279

Authors

A. Seet1, S.P. Choo2, D.W.M. Tai3, Y.C.J. Lam1, W.T. Teng4, C. Lim5, T.K.H. Lim6, I.B. Tan3, E. Petricoin7, M. Ng8

Author affiliations

  • 1 Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 2 Medical Oncology, National Cancer Center Singapore, 169610 - Singapore/SG
  • 3 Division Of Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 4 Cte, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 5 Biostatistics, Cte, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 6 Department Of Pathology, Singapore General Hospital, 169608 - Singapore/SG
  • 7 Applied Proteomics And Molecular Medicine, Institute of Biomedical Innovation, George Mason University, 20110 - Manassas/US
  • 8 Division Of Medical Oncology, National Cancer Centre (NCC), Singapore, 169610 - Singapore/SG
More

Resources

Abstract 2124

Background

Varlitinib (VAR, ASLAN001) is a potent pan-HER oral tyrosine kinase inhibitor, with efficacy in EGFR mutant and HER2 over-expressing tumours. We evaluated the safety, tolerability and maximum tolerated dose (MTD) of VAR with CAPOX (COX) and mFolfox6 (FOL), in pts with advanced solid tumours.

Methods

Eligible pts had advanced solid tumours, ECOG performance status (PS) 0-1 and adequate organ function. Colorectal cancer (CRC) with RAS/RAF mutations were excluded. COX (Capecitabine 850mg/m2 BID D1-D14 with oxaliplatin (OX) 130mg/m2 IV D1, Q21 days) or mFolfox6 (5-FU 400mg/m2 IV bolus D1 and 2400mg/m2 over 46 hrs with OX 85mg/m2 IV D1, Leucovorin 400mg/m2 IV D1, Q14 days) was given with VAR 200-400mg BID. Maximum 6 cycles COX or 9 cycles FOL, followed by VAR alone. Dose-limiting toxicity (DLT) period was 2 cycles.

Results

30 pts were enrolled, 9 COX and 21 FOL arm. 15 (52%) CRC (all prior OX), 6 (21%) cholangiocarcinoma (CC), 3 (10%) gallbladder cancer and 6 (20%) others. Sex M/F 13/17, median age (range), PS, lines of prior chemo was 62yrs (36-71), 1(0-1) and 3.5(0-7) respectively. 28 pts were evaluable for MTD. MTD of VAR was 300mg/BID when given with FOL or COX.Table: 430P

DosePt enrolled/ evaluableDLT
COX + VAR 400mg/BID3/2G3 Fatigue x2
COX + VAR 300mg/BID6/6G3 Fatigue
FOL + VAR 400mg/BID4/4G4 Transaminitis, G3 Raised Bilirubin
FOL + VAR 300mg/BID11/9G4 Encephalopathy, G3 Rash
FOL + VAR 200mg/BID6/6G3 Encephalopathy

Grade 3/4 AEs (occurring ≥ 5%): neutropenia 5 (17%), fatigue 3(10%), transaminitis 2(7%), diarrhoea 2(7%), febrile neutropenia 2(7%), transient metabolic encephalopathy 2(7%). Of 28 pts evaluable for response, 3 (11%) had PR and 16 (57%) SD. Disease control rate (PR+SD) for ≥ 12wks was 13 (46%). 5 (18%) had long PFS (223-645 days), comprising a gallbladder and CRC (both HER2-overexpressing, prior platinum), CC, bladder and CRC (prior OX and cetuximab). PK analysis did not show VAR accumulation. Plasma cell free DNA and HER pathway inhibition results will be presented later.

Conclusions

MTD for VAR with COX and FOL was 300mg/BID. Durable efficacy was seen in biliary cancers and CRC. ASLAN pharmaceuticals and the Singapore National Medical Research Council supported this study.

Clinical trial identification

NCT02435927.

Legal entity responsible for the study

National Cancer Centre, Singapore.

Funding

Aslan Pharmaceuticals.

Editorial Acknowledgement

Disclosure

M. Ng: Member: Aslan Pharmaceuticals advisory board; Speaker and research funding: Industry associated funding. All other authors have declared no conflicts of interest.

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