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ePoster Display

1384P - DKN-01 in combination with tislelizumab and chemotherapy as a first-line therapy in unselected patients with advanced gastroesophageal adenocarcinoma (GEA): DisTinGuish trial

Date

16 Sep 2021

Session

ePoster Display

Topics

Cytotoxic Therapy;  Clinical Research;  Immunotherapy

Tumour Site

Oesophageal Cancer;  Gastric Cancer

Presenters

Samuel Klempner

Citation

Annals of Oncology (2021) 32 (suppl_5): S1040-S1075. 10.1016/annonc/annonc708

Authors

S.J. Klempner1, C. Sirard2, J. Chao3, V. Chiu4, D. Mahalingam5, H. Uronis6, M. Kagey7, J. Baum7, F. Dayyani8, J. Song9, J. Wang10, S. Iqbal11, M. Tejani12, M.B. Sonbol13, A.J. Scott14, Z.A. Wainberg15, J.A. Ajani16

Author affiliations

  • 1 Mass General Hospital Cancer Center, Massachusetts General Hospital, 02114 - Boston/US
  • 2 Clinical Development, Leap Therapeutics, 02141 - Cambridge/US
  • 3 Department Of Medical Oncology & Therapeutics Research, City of Hope, 91010 - Duarte/US
  • 4 Gastrointestinal Oncology & Molecular Precision, TheAngelesClinic& Research Institute, Los Angeles/US
  • 5 Robert H. Lurie Comprehensive Cancer Center, Northwestern Memorial Hospital, 60611 - Chicago/US
  • 6 Medical Oncology, Duke University Medical Center, Durham/US
  • 7 Translational Research, Leap Therapeutics, Inc., Cambridge/US
  • 8 Uc Irvine Health, University of California, Irvine, 92868 - Orange/US
  • 9 Biostatistics, BeiGene, Ltd, Beijing/CN
  • 10 Clinical Research, BeiGene, Ltd, Beijing/CN
  • 11 Medical Oncology, USC Keck School of Medicine, Norris Cancer Center, Los Angeles/US
  • 12 Medical Oncology, AdventHealth Cancer Institute, Orlando/US
  • 13 Internal Medicine Department, Mayo Clinic Cancer Center, 85054 - Phoenix/US
  • 14 Medical Oncology, University of Arizona Cancer Center, Tuscon/US
  • 15 Medicine, Hematology & Oncology, UCLA Santa Monica Medical Center, 90404 - Santa Monica/US
  • 16 Gi Medical Oncology, The University of Texas MD Anderson Cancer Center, 77030-4095 - Houston/US

Resources

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Abstract 1384P

Background

Dickkopf-1 (DKK1) modulates Wnt signaling and contributes to an immune suppressive tumor microenvironment. DKN-01 (D), a neutralizing DKK1 antibody, in combination with an anti-PD1 antibody, has demonstrated safety and clinical activity in advanced previously treated DKK1-high GEA. We report response and survival outcomes in GEA patients (pts) treated with D + tislelizumab (T) + capecitabine/oxaliplatin (CAPOX) as a first line therapy.

Methods

We enrolled advanced GEA pts in a phase IIa study of D + T + CAPOX (NCT04363801). Tumoral DKK1 mRNA expression was assessed by a chromogenic in situ hybridization RNAscope assay and assigned an H-score (0-300). Objective response rate (ORR) [primary efficacy objective], duration of response (DoR), disease control rate (DCR), and progression free survival (PFS) were evaluated in a modified intent to treat (mITT) population (completed ≥ 1 cycle) as well as compared between DKK1 high (H-score ≥35) and low groups.

Results

Twenty-five GEA pts were enrolled. Median age was 61 (22, 80); 19 males, 6 females. 17 pts (68%) had gastroesophageal junction (GEJ) adenocarcinoma; 8 pts (32%) had gastric cancer (GC). 18 GEA pts had RNAscope DKK1 expression available; 9 pts DKK1-high [5 GEJ, 4 GC) and 9 pts DKK1-low [7 GEJ, 2 GC]. Mean duration of treatment 3 mos, longest duration to date on study 7 mos, 19 pts remain on therapy. Most common D + T + CAPOX regimen related TEAEs were G1/2: anemia, thrombocytopenia, fatigue, diarrhea, nausea each in 3 pts. No related G3/4 toxicities; overall four G5 events; 1 related event pulmonary embolism. mITT analysis included 22 pts. Preliminary ORR in response evaluable (RE) mITT was 68% (13 PR, 6 SD, 1 NE, 2 pending first scan) and DCR 100%. In RE DKK1 high pts (n=7) there was an ORR of 100% (6 PR, 1 NE) compared with DKK1 low pts (n=9) ORR of 56% (5 PR, 4 SD). Median DoR and PFS were not reached.

Conclusions

D + T + CAPOX was well tolerated and has encouraging early activity as first line treatment for advanced GEA (unselected for PD-L1), with a preliminary ORR of 68% and DCR of 100%. Higher ORR in biomarker RE population: DKK1 high compared with DKK1 low (ORR 100% vs 56%). Updated ORR, DoR, PFS and PD-L1 expression will be reported.

Clinical trial identification

NCT04363801.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Leap Therapeutics, Inc.

Disclosure

S.J. Klempner: Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Astellas; Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Merck; Financial Interests, Personal, Advisory Board, One Time Advisory Board: Natera; Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Pieris; Financial Interests, Personal, Stocks/Shares, Stock Ownership: Turning Point Therapeutics; Financial Interests, Personal and Institutional, Other, Local PI: Astellas; Non-Financial Interests, Institutional, Principal Investigator, Coordinating PI: Leap Therapeutics; Non-Financial Interests, Institutional, Other, Local PI: Macrogenics; Non-Financial Interests, Personal, Advisory Role, Medical Scientific Advisory Board Member: Debbies Dream Foundation; Non-Financial Interests, Personal, Advisory Role, Member of Scientific Advisory Board: Hope for Stomach Cancer; Non-Financial Interests, Personal, Other, Member of Gastric and Esophageal NCCN guideline committees: NCCN. C. Sirard: Financial Interests, Personal, Full or part-time Employment: Leap Therapeutics, Inc. J. Chao: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Other, consulting: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, consulting: Lilly; Financial Interests, Personal, Advisory Board: Macrogenics; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Other, consulting: Ono Pharmaceuticals; Financial Interests, Personal, Other, consulting: Roche; Financial Interests, Personal, Advisory Board: Turning Point Therapeutics; Financial Interests, Institutional, Funding, Financial interest: Brooklyn Immunotherapeutics; Financial Interests, Institutional, Other, Financial interest: Merck. V. Chiu: Financial Interests, Institutional, Other, Local PI: Seattle Genetics/Astellas; Financial Interests, Institutional, Other, Local PI: Arcus Biosciences; Financial Interests, Institutional, Other, Local PI: Leap Therapeutics; Financial Interests, Institutional, Other, Local PI: Intra-IMMUSG Pte Ltd; Financial Interests, Institutional, Other, Local PI: Alkermes; Financial Interests, Institutional, Other, Local PI: Incyte. D. Mahalingam: Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Speaker’s Bureau: Exelixis; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Advisory Board: BMS. H. Uronis: Financial Interests, Institutional, Other, Local PI: Merck; Financial Interests, Institutional, Other, Local PI: Macrogenics; Financial Interests, Institutional, Other, Local PI: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Institutional, Other, Local PI: Leap Therapeutics; Financial Interests, Personal, Other, Consultant- DSMB: AstraZeneca; Financial Interests, Institutional, Other, Local PI: Genetech. M. Kagey: Financial Interests, Personal, Full or part-time Employment: Leap Therapeutics, Inc. J. Baum: Financial Interests, Personal, Full or part-time Employment: Leap Therapeutics, Inc. F. Dayyani: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Deciphera; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Exelixis; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: FMI; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: QED; Financial Interests, Personal, Invited Speaker: Signatera; Financial Interests, Personal, Advisory Board: Signatera; Financial Interests, Personal, Invited Speaker: Sirtex; Non-Financial Interests, Institutional, Other, Local PI: AstraZeneca; Non-Financial Interests, Institutional, Other, Local PI: Bayer; Non-Financial Interests, Institutional, Other, Local PI: BMS; Non-Financial Interests, Institutional, Other, Coordinating PI: Exelixis; Non-Financial Interests, Institutional, Other, Local PI: Ipsen; Non-Financial Interests, Institutional, Other, Local PI: Merck; Non-Financial Interests, Institutional, Other, Local PI: Roche; Non-Financial Interests, Institutional, Other, Coordinating PI: Signatera; Non-Financial Interests, Institutional, Other, Coordiating PI: Taiho; Non-Financial Interests, Institutional, Other, Local PI: Tishula. J. Song: Financial Interests, Personal, Full or part-time Employment: BeiGene, Ltd. J. Wang: Financial Interests, Personal, Full or part-time Employment: BeiGene, Ltd. S. Iqbal: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Speaker series to faculty on esophageal cancer: BeiGene; Financial Interests, Personal, Advisory Board: Eisai. A.J. Scott: Financial Interests, Personal, Invited Speaker: ACCC; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: QED; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson; Financial Interests, Personal, Other, Local PI: Eli Lilly; Financial Interests, Personal, Other, Local PI: Incyte; Financial Interests, Personal, Other, Local PI: Leap Therapeutics; Financial Interests, Personal, Other, Local PI: Macrogenics; Financial Interests, Personal and Institutional, Other, Local PI: Merck; Financial Interests, Personal, Other, Local PI: Seagen. Z. Wainberg: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Five Prime; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: Arcus; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Molecular Templates; Financial Interests, Personal, Advisory Board: Array; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Five Prime; Financial Interests, Institutional, Research Grant: Gilead; Financial Interests, Institutional, Research Grant: Arcus; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Molecular Therapeutics; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Array/Pfizer. J.A. Ajani: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Taiho; Financial Interests, Personal, Advisory Role: More Health; Financial Interests, Personal, Advisory Role: Zymeworks; Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Advisory Role: Dava; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Acrotech; Financial Interests, Personal, Advisory Role: Daiichi; Financial Interests, Personal, Advisory Role: Vaccinogen; Financial Interests, Personal, Advisory Role: Innocent; Financial Interests, Personal, Advisory Role: Merck Serrono; Financial Interests, Personal, Advisory Role: Oncotherics; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: OncLive; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Turning Point; Financial Interests, Personal, Advisory Role: GRAIL; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Delta Fly; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Prolinix; Financial Interests, Institutional, Research Grant: Zymeworks; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: Leap; Financial Interests, Institutional, Research Grant: Gilead. All other authors have declared no conflicts of interest.

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