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
4294 - The Patient Voice: An Irish Survey of Nutrition Attitudes & Access to Dietetic Care Throughout the Cancer Journey
Presenter: Erin Stella Sullivan
Session: Poster Display session 1
Resources:
Abstract
1925 - Homcology: home chemotherapy delivery in a simultaneous care project for frail advanced cancer patients
Presenter: Claudio Chini
Session: Poster Display session 1
Resources:
Abstract
4701 - Treatment-related adverse events and tolerability in patients with advanced non-squamous non-small cell lung cancer treated with first-line checkpoint inhibitors in combination with chemotherapy
Presenter: Ruth D'cunha
Session: Poster Display session 1
Resources:
Abstract
2985 - Clinical utility of a systematic toxicity assessment form (STAF) in patients with breast cancer receiving adjuvant or neoadjuvant therapy.
Presenter: Jwa Hoon Kim
Session: Poster Display session 1
Resources:
Abstract
2358 - Physicians’ satisfaction with Health-related quality of life (HRQoL) assessment in daily clinical practice using electronic patient-reported outcome (ePRO) for cancer patients.
Presenter: Guillaume Mouillet
Session: Poster Display session 1
Resources:
Abstract
5172 - Predictors of Survival in Patients with Incurable Cancer
Presenter: Erin Stella Sullivan
Session: Poster Display session 1
Resources:
Abstract
2281 - Patients and Physicians' Satisfaction with Telemedicine (TM) in Cancer Care and Factors that Correlate with a Positive Patient’s Experience
Presenter: Hurria Gondal
Session: Poster Display session 1
Resources:
Abstract
2193 - Adherence to ESMO 2014 guidelines on bone-targeting agent (BTA) initiation for breast and prostate cancer patients: real-world insights from practicing European physicians
Presenter: Alex Rider
Session: Poster Display session 1
Resources:
Abstract
2200 - Use of skeletal-related events preventive agents in patients with solid tumours and bone metastases in central Denmark
Presenter: Anders Boysen
Session: Poster Display session 1
Resources:
Abstract
2504 - Inadequacy of current definition and staging system of Medication-Related Osteonecrosis of Jaw (MRONJ) released by AAOMS : a Computed Tomography study in 151 cancer and myeloma patients
Presenter: Vittorio Fusco
Session: Poster Display session 1
Resources:
Abstract