Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

4148 - Safety and Efficacy of a DKK1 Inhibitor (DKN-01) in Combination with Pembrolizumab (P) in Patients (Pts) with Advanced Gastroesophageal (GE) Malignancies


21 Oct 2018


Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology


Clinical Research;  Immunotherapy

Tumour Site

Oesophageal Cancer;  Gastric Cancer


Samuel Klempner


Annals of Oncology (2018) 29 (suppl_8): viii205-viii270. 10.1093/annonc/mdy282


S.J. Klempner1, J. Bendell2, V. Meucci Villaflor3, L. Tenner4, S. Stein5, C.A. Sirard6, W. Newman7, M. Kagey7, K. Schlienger8, J. Strickler9

Author affiliations

  • 1 Medical Oncology, The Angeles Clinic and Research Institute, 90025 - Los Angeles/US
  • 2 Gi Oncology Research, Sarah Cannon Research Institute/Tennessee Oncology, 37923 - Nashville/US
  • 3 Medical Oncology, Northwestern University Feinberg School of Medicine, 60611 - Chicago/US
  • 4 Medical Oncology, University of Texas Health Science Center, San Antonio/US
  • 5 Medical Oncology, Yale School of Medicine, New Haven/US
  • 6 Medical Oncology, Leap Therapeutics, Inc., Cambridge/US
  • 7 Research, Leap Therapeutics, Inc., Cambridge/US
  • 8 Oncology, Merck & Co, Kenilworth/US
  • 9 Medical Oncology, Duke University Medical Center, Durham/US

Abstract 4148


Dickkopf-1 (DKK1) is a modulator of the Wnt and PI3K/AKT signaling pathways and contributes to an immunosuppressive tumor microenvironment by activating MDSCs and Tregs. DKN-01 (D), an mAb against DKK1, acts on innate immune cells, and in preclinical studies demonstrates upregulation of both PD-L1 and IFNγ-related chemokines, suggesting a role for immune checkpoint combination. Anti-PD-1 plus DKN-01 shows additive antitumor effects in the B16 syngeneic mouse model; clinical studies are underway. GE cancers commonly overexpress DKK1 and harbor Wnt pathway alterations.


Phase 1b study to evaluate dose, safety and efficacy of D (150 mg or 300 mg on Days 1 & 15) plus P (200 mg on Day 1) of each 21-day cycle in pts with advanced GE cancer. Safety, efficacy, and correlative analyses (cytokines, PBMC immunophenotyping, tumor genomics and intra-tumoral DKK1/PD-L1) are ongoing.


Pts enrolled in 2 cohorts: D (150 mg [n = 2] or 300 mg [n = 11]) + P. All 13 pts had adenocarcinomas (4 pts: EC, 6 pts: GEJ, 3 pts: GC). Three pts (23%) were refractory to prior checkpoint inhibitor, and only 1 pt was known to be PD-L1+ at study entry. No DLTs or treatment related SAEs were observed. Most TEAE were Grade 1/2 and commonly gastrointestinal disorders. ≥Grade 3 TEAE included hyponatremia & anorexia (each 2 pts), lymphopenia, transfusion reaction, GI bleed, abdominal pain, dehydration, weight loss, thrombotic event & weakness (each 1 pt); only lymphopenia felt related to D. Among 9 evaluable patients there was one confirmed PR, SD in 5 pts (including one IO-refractory pt with minor response) and PD in 3 pts. The 6-week disease control rate was 75%; 6 pts remain on therapy. Most PR/SD pts have had downward trend of peripheral MDSC; more evident in pt with PR. Complete cohort details and correlative work will be presented.


Preliminary results demonstrate that D + P is well tolerated with no new safety signals and shows encouraging early efficacy signals in advanced GE cancer. A subset of pts with features typically associated with lower response to single agent anti-PD-1 therapy (KRAS amp, PD-L1 neg, and MSS) exhibited prolonged clinical benefit and warrant further study. Expansion to confirm efficacy is ongoing.

Clinical trial identification


Legal entity responsible for the study

Leap Therapeutics, Inc.


Leap Therapeutics, Inc.

Editorial Acknowledgement


S.J. Klempner: Consultant/advisory: Lilly, Astellas; Research funding (institutional): Leap, Merck, Incyte. J. Bendell: Gilead, Genentech, BMS, Five Prime, Lilly, Merck, MedImmune, Celgene, EMD Serono, Taiho, Macrogenics, GSK, Novartis, OncoMed, Leap, TG Therapeutics, AstraZeneca, BI, Daiichi Sankyo, Bayer, Incyte, Apexigen, Roche, Koltan, SynDevRx, Forty Seven, Abbvie, StemCentrix, Array, Onyx, Sanofi, Takeda, Abbott, Eisai, Celldex, Agios, ARMO, CytoMx, Nektar, ARMO, Boston Biomedical, Ipsen, Merrimack, Novartis, Tarveda, Tyrogenex, Oncogenex, Marshall Edwards, Pieris, Mersana, Calithera, Blueprint, Gritstone, Evelo, FORMA, Forty Seven, EMD Serono, Merus. V. Meucci Villaflor: Advisory board: Takeda, Genentech. S. Stein: Advisory board: Genentech/Roche, Merck. C.A. Sirard, W. Newman, M. Kagey: Employee: Leap Therapeutics, Inc. including compensation, stock options and travel award. K. Schlienger: Employee: Merck & Co, USA with compensation, stock option and travel award. J. Strickler: Research support: Leap Therapeutics. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.