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
3266 - Morphology of tumor-associated macrophages dictates the prognosis of patients with colorectal liver metastases.
Presenter: Matteo Donadon
Session: Poster Display session 2
Resources:
Abstract
1694 - Pembrolizumab (pembro) Plus mFOLFOX or FOLFIRI in Patients With Metastatic Colorectal Cancer (mCRC): KEYNOTE-651 Cohorts B and D
Presenter: Richard Kim
Session: Poster Display session 2
Resources:
Abstract
908 - Romidepsin (FK228) Regulates the Expression of the Immune Checkpoint Ligand PD-L1 and Exerts Synergistic Anti-Tumor Activity with an Anti-PD-1 Antibody in Colon Cancer
Presenter: Hui Li
Session: Poster Display session 2
Resources:
Abstract
3127 - Prognostic significance of circulating regulatory T lymphocytes (Tregs) in patients with metastatic colorectal cancer (mCRC) under treatment with first line chemotherapy.
Presenter: Zafeiris Zafeiriou
Session: Poster Display session 2
Resources:
Abstract
5416 - The SAFFO study: Sex-related prognostic role And cut-oFf deFinition of monocyte-to-lymphocyte ratio (MLR) in metastatic colOrectal cancer
Presenter: Camilla Lisanti
Session: Poster Display session 2
Resources:
Abstract
2518 - SPICE, a phase I study of enadenotucirev in combination with nivolumab in tumors of epithelial origin: analysis of the metastatic colorectal cancer patients in the dose escalation phase
Presenter: Marwan Fakih
Session: Poster Display session 2
Resources:
Abstract
4000 - Phase 1/2 study with CXCL12 inhibitor NOX-A12 and pembrolizumab in patients with microsatellite-stable, metastatic colorectal or pancreatic cancer
Presenter: Niels Halama
Session: Poster Display session 2
Resources:
Abstract
2223 - Microsatellite Instability Status in Metastatic Colorectal Cancer and Effect of Immune Checkpoint Inhibitors on Survival in MSI-High Metastatic Colorectal Cancer
Presenter: Wataru Okamoto
Session: Poster Display session 2
Resources:
Abstract
2569 - Phase II trial of Trametinib (T) and Panitumumab (Pmab) in RAS/RAF wild type (wt) metastatic colorectal cancer (mCRC)
Presenter: Kanan Alshammari
Session: Poster Display session 2
Resources:
Abstract
5402 - Microsatellite instability and immunogenicity in colorectal cancer – do resident memory Tcells (Trm) play a role in colorectal cancer
Presenter: Wei Toh
Session: Poster Display session 2
Resources:
Abstract