Abstract 1311
Background
VAR is a potent TKI against EGFR, HER2 and HER4. Efficacy of VAR combined with fluoropyrimidine and platinum chemo in colorectal cancer (CRC) and biliary tract cancer (BTC) has been reported (ESMO 2018 430P, GI ASCO 2019 #319).
Methods
Patients (pts) ECOG PS 0-1 with advanced solid tumors and adequate organ function were eligible. Homozygous UGT1A1*6/*6 and *28/*28 pts were excluded. VAR was combined with mFOLFIRI up to 9 cycles followed by VAR monotherapy. Each cycle was 14 days with dose limiting toxicity (DLT) period of 28 days. VAR was evaluated at 3 dose levels (DL): DL1 200mg/BD D1-14; DL2 200mg/BD D4-11; DL3 300mg/BD D4-11. Dose escalation by 3 + 3 design. Primary endpoint was safety and maximum tolerated dose (MTD). Secondary endpoints were pharmacokinetics (PK) and response. Tumor NGS (Oncomine OCP v3) and IHC (HER2, cMET, PTEN) were performed.
Results
As of 15-Feb-19, 16 pts were treated, 5 (31%) BTC, 5 (31%) CRC, 3 (19%) gastroesophageal, 2 (13%) pancreatic and 1 (6%) ovarian clear cell cancer (OCCC). Sex M/F 13/3, median (range) for age was 62yrs (45-79), ECOG 0 (0-1) and lines of prior therapy was 3 (0-6). 4/4 pts at DL1 had G3/4 neutropenia on cycle 2 D1 lasting <7 days, possibly by VAR inhibition of UGT1A1 mediated-clearance of SN-38. Intermittent dosing of VAR in DL2 (n = 5) and DL3 (n = 6) was tolerable with a DLT of G3 stomatitis (HSV co-infection) at DL3. PK study showed widely variable VAR levels but no VAR accumulation. VAR was not escalated as prior studies showed limited tolerability at 400mg/BD combined with chemo. G3/4 treatment related adverse events (TRAE) seen in ≥ 10% of pts was neutropenia (44%; 4 DL1, 1 DL2, 2 DL3) with no events of neutropenic sepsis. Of the 16 pts, 2 (13%) had PR (BTC, 1 prior line; HER2 over-expressing OCCC, 6 prior lines) maintained at 7.5 and 6.1 mths respectively, 9 (56%) had disease control (DCR, PR+SD) of which in 4 (25%) DCR was >6 mths, and median PFS was 4.2 mths. HER2 alterations were seen in 4 pts (1 PR, 2 SD, 1 PD).
Conclusions
VAR 300mg/BD D4-11 combined with mFOLFIRI is the MTD and well tolerated. Durable response in HER2 positive OCCC was seen and warrants further investigation.
Clinical trial identification
NCT02435927.
Editorial acknowledgement
Legal entity responsible for the study
National Cancer Centre Singapore.
Funding
National Medical Research Council (NMRC) Singapore, ASLAN Pharmaceuticals.
Disclosure
A.C. Tan: Travel / Accommodation / Expenses: ASLAN Pharmaceuticals. M.C.H. Ng: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): ASLAN Pharmaceuticals. All other authors have declared no conflicts of interest.
Resources from the same session
3620 - Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
Presenter: Wolfgang Wick
Session: Poster Display session 1
Resources:
Abstract
5465 - Proof of concept clinical study by US-guided intratumor injection of VCN-01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer
Presenter: Manuel Hidalgo
Session: Poster Display session 1
Resources:
Abstract
2555 - A Phase 1a/b first-in-human, open-label, dose-escalation, safety, PK and PD study of TP-0903 in solid tumors
Presenter: John Sarantopoulos
Session: Poster Display session 1
Resources:
Abstract
3533 - First in human phase 1/2a study of PEN-866, a Heat Shock Protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumors: Phase 1 results
Presenter: Johanna Bendell
Session: Poster Display session 1
Resources:
Abstract
4114 - A Phase I Open-Label, Non-Randomized Study of Recombinant Super-Compound Interferon (rSIFN-co) In Patients with Advanced Solid Tumors
Presenter: Amanda Seet
Session: Poster Display session 1
Resources:
Abstract
2537 - Evaluation of Pharmacodynamic (PD) Biomarkers in Advanced Cancer Patients Treated with Oxidative Phosphorylation (OXPHOS) Inhibitor, OPC-317 (OPC)
Presenter: Jie Qing Eu
Session: Poster Display session 1
Resources:
Abstract
5764 - Pharmacokinetic (PK) assessment of BT1718: A phase 1/2a study of BT1718, a first in class Bicycle Toxin Conjugate (BTC), in patients (pts) with advanced solid tumours
Presenter: Natalie Cook
Session: Poster Display session 1
Resources:
Abstract
2683 - A phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumors.
Presenter: Wael Harb
Session: Poster Display session 1
Resources:
Abstract
3609 - Interim Results from Trial of SL-801, a Novel XPO-1 Inhibitor, in Patients with Advanced Solid Tumors
Presenter: Judy Wang
Session: Poster Display session 1
Resources:
Abstract
3485 - Phase 1 Trial of Fruquintinib in Patients with Advanced Solid Tumors: Results of the Dose Escalation Phase
Presenter: Andrea Wang-Gillam
Session: Poster Display session 1
Resources:
Abstract