Abstract 3303
Background
In pancreatic cancer desmoplasia is a central feature of the tumour microenvironment. Growing evidence suggests that by targeting both tumour cells and tumour stoma, treatment efficacy is increased. LDE225 is a pharmacological Hedgehog signaling pathway inhibitor and is thought to specifically target tumour stroma. We investigated the combined use of LDE225 and chemotherapy in pancreatic cancer.
Methods
This was a multi-center, dose finding, phase I/II study for patients with metastatic pancreatic cancer. In part I of the study, we established the maximum tolerated dose of LDE225 to be 200 mg once daily co-administered with gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 of a 4 week cycle (ESMO 2017). The objective of the phase II part was to evaluate efficacy and safety of the treatment combination and assess tumour cellularity and vascularity with diffusion weighted magnetic resonance imaging and dynamic contrast enhanced magnetic resonance imaging. Tumour response evaluation was performed using CT scan. Here we report on the phase II part of the study.
Results
In the phase II part we included 25 patients. Most patients had WHO performance status of 0-1 (92%) and 60% were male. All patients received prior chemotherapy. Patients were treated with a median number of two cycles (IQR 1.5-5.0). Four therapy related grade 4 adverse events (AE) were observed: sepsis (2), neutropenia (2), and one grade 5 (sepsis). Most common grade 3 therapy related AEs were neutropenia (37%) and diarrhea (14.8%). Patients discontinued treatment because of progressive disease (20), bacterial infection (1), sepsis (1) and diminished quality of life (1). 2 patients are still alive. In 19 patients target lesion response was evaluable, 2 patients had partial response (10%), stable disease was seen in 10 patients (53%) and 7 patients had progressive disease (37%). The median overall survival was 6 months (IQR 3.0-8.5). Tumour vascularity and cellularity is currently being analyzed in 25 patients.
Conclusions
This study shows that LDE225 in combination with gemcitabine and nab-paclitaxel is well-tolerated in patients with metastatic pancreatic cancer and has promising efficacy.
Clinical trial identification
NCT02358161.
Editorial acknowledgement
Legal entity responsible for the study
J.W. Wilmink.
Funding
Novartis, Celgene and Sunpharma.
Disclosure
H.W.M. van Laarhoven: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Lily; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Serono; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Nordic; Research grant / Funding (institution): Philips. H.W. Wilmink: Research grant / Funding (institution): Servier; Research grant / Funding (institution): Halozyme; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Advisory / Consultancy: Shire. All other authors have declared no conflicts of interest.
Resources from the same session
1109 - First Canadian Interim Analysis from the Phase IIIb CompLEEment-1 Ribociclib + Letrozole HR+ HER2- Advanced Breast Cancer Trial
Presenter: Cristiano Ferrario
Session: Poster Display session 2
Resources:
Abstract
4401 - Real-world effectiveness of first-line palbociclib + letrozole for metastatic breast cancer 4 years post approval in the US
Presenter: Jonathan Kish
Session: Poster Display session 2
Resources:
Abstract
5876 - Palbociclib-Fulvestrant (PALBO-FUL) and Everolimus -Exemestane (EVE-EXE) for Second line Hormonal Treatment (HT) of Metastatic Breast Cancer (MBC) with Lobular Histology: a Propensity Score Matched Analysis of a Multicenter ‘Real-World’ Patients (pts) Series.
Presenter: Armando Orlandi
Session: Poster Display session 2
Resources:
Abstract
3587 - Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)
Presenter: E Dees
Session: Poster Display session 2
Resources:
Abstract
5696 - Final results of the STEM trial: SFX-01 in the Treatment and Evaluation of ER+ Her2- Metastatic breast cancer (mBC)
Presenter: Sacha Howell
Session: Poster Display session 2
Resources:
Abstract
1475 - Alpelisib (ALP) + Fulvestrant (FUL) in Hormone-Receptor Positive (HR+), Human Epidermal Growth Factor Receptor-2–Negative (HER2–) Advanced Breast Cancer (ABC): Subgroup Analysis by Presence of Visceral Metastasis (VM) in the SOLAR-1 Trial
Presenter: Mario Campone
Session: Poster Display session 2
Resources:
Abstract
2549 - Phase 1 Dose Escalation Study of a Selective Androgen Receptor Modulator RAD140 in Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) Breast Cancer (BC)
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3787 - A Phase I study of XZP-3287, a novel oral CDK4/6 Inhibitor, administered on a continuous dosing schedule, in patients with advanced solid tumours
Presenter: Binghe Xu
Session: Poster Display session 2
Resources:
Abstract
4835 - Phase-I dose-escalation and expansion study of the PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors
Presenter: Huiping Li
Session: Poster Display session 2
Resources:
Abstract
5083 - Phase 2 study of DHP107 (Liporaxel®, oral paclitaxel) in first-line, HER2 negative recurrent/metastatic breast cancer (OPTIMAL study, NCT03315364)
Presenter: Jin-Hee Ahn
Session: Poster Display session 2
Resources:
Abstract