Phase 2 Study Evaluating the Efficacy of the Combination of DKN-01 (DKK1 Inhibitor, Leap Therapeutics) and Pembrolizumab in the Treatment of Advanced or Recurrent Endometrial Cancer

To learn if the combination of DKN-01 and pembrolizumab can help to control advanced or recurrent endometrial cancer.

Start Date29 Aug 2023

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+3]

NCT05480306

/ CompletedPhase 2

Randomized Phase 2 Study of DKN-01 Plus FOLFIRI/FOLFOX and Bevacizumab Versus FOLFIRI/FOLFOX and Bevacizumab as Second-line Treatment of Advanced Colorectal Cancer (DeFianCe)

This is a Phase 2 randomized, open-label, two-part, multicenter study with a safety run-in to evaluate efficacy and safety of DKN-01 plus FOLFIRI/FOLFOX and bevacizumab versus standard of care (SOC) [FOLFIRI/FOLFOX and bevacizumab] as second-line treatment of advanced CRC patients.

Start Date30 Aug 2022

Sponsor / Collaborator

Leap Therapeutics, Inc.

NCT04363801

/ TerminatedPhase 2

A Phase 2, Multicenter, Open-Label Study of DKN-01 in Combination With Tislelizumab ± Chemotherapy as First-Line or Second-Line Therapy in Adult Patients With Inoperable, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (DisTinGuish)

A Phase 2, Multicenter, Open-Label Study of DKN-01 in Combination with Tislelizumab ± Chemotherapy as First-Line or Second-Line Therapy in Adult Patients with Inoperable, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Start Date29 Jul 2020

Sponsor / Collaborator

Leap Therapeutics, Inc.

[+1]

100 Clinical Results associated with Sirexatamab

100 Translational Medicine associated with Sirexatamab

100 Patents (Medical) associated with Sirexatamab

Literatures (Medical) associated with Sirexatamab

01 Feb 2025·APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY

DKN-01 Suppresses Gastric Cancer Progression Through Activating cGAS-STING Pathway to Block Macrophage M2 Polarization

Article

Author: Qi, Yingying ; Wang, Sisi ; Yang, Xiaohuan

Dickkopf-1 (DKK1) is a secretory antagonist that can bind with the Wnt coreceptor to desensitize cells to canonical Wnt ligands. DKN-01 is a specific antibody targeting secreted DKK1, which has been investigated as a monotherapy or combination therapy for various malignant tumors, including gastric cancer (GC). Tumor-associated macrophages (TAMs) with high plasticity usually present M2 phenotype, which can promote tumor progression. The aim of this study was to investigate the effect of DKN-01 on macrophage polarization in GC and the underlying molecular mechanism. To ascertain the effect of DKN-01 on GC tumor growth, we established a tumor-bearing mouse model and found that DKN-01 treatment suppressed tumor growth efficiently. Through RNA-seq and pathway enrichment analysis, we identified that the differentially expressed genes after DKN-01 treatment are associated with tumor immune-related pathways. Macrophage polarization was assessed using immunohistochemistry and quantitative real-time polymerase chain reaction. DKN-01 and knockdown of DKK1 promoted M1 polarization and inhibited M2 polarization of macrophages, while DKK1 overexpression got the opposite results. Moreover, DKN-01 activated the cGAS/STING pathway, while the inactivation of cGAS-STING pathway using RU.521 reversed the inhibition of tumor growth in vivo and macrophage M2 polarization caused by DKN-01. This study reveals that DKN-01 suppresses GC tumor growth through activating cGAS-STING pathway to block macrophage M2 polarization.

01 Jun 2024·Hematology/oncology clinics of North America

Targeted Agents in Esophagogastric Cancer Beyond Human Epidermal Growth Factor Receptor-2

Review

Author: Mehlhaff, Eric ; Miller, Devon ; Ebben, Johnathan D ; Uboha, Nataliya V ; Dobrzhanskyi, Oleksii

Gastroesophageal cancers are highly diverse tumors in terms of their anatomic and molecular characteristics, making drug development challenging. Recent advancements in understanding the molecular profiles of these cancers have led to the identification of several new biomarkers. Ongoing clinical trials are investigating new targeted agents with promising results. CLDN18.2 has emerged as a biomarker with established activity of associated targeted therapies. Other targeted agents, such as bemarituzumab and DKN-01, are under active investigation. As new agents are incorporated into the treatment continuum, the questions of biomarker overlap, tumor heterogeneity, and toxicity management will need to be addressed.

01 May 2023·Gynecologic oncology

DKK1 is a predictive biomarker for response to DKN-01: Results of a phase 2 basket study in women with recurrent endometrial carcinoma

Article

Author: LyBarger, Kristopher ; Matulonis, Ursula ; Sachdev, Jasgit ; Duska, Linda R ; Piper, Diane ; Birrer, Michael ; Barroilhet, Lisa M ; Hamilton, Erika ; Sirard, Cynthia A ; Kagey, Michael H ; Goodman, Howard M ; Castro, Cesar ; Arend, Rebecca ; Bradley, William ; ElNaggar, Adam C ; Jackson, Camille Gunderson ; Dholakia, Jhalak ; O'Malley, David M ; Mahdi, Haider ; Liu, Amy

PURPOSE:

Dickkopf-1 (DKK1) is a Wnt signaling modulator promoting tumor growth, metastasis, angiogenesis, and immunosuppression by regulating innate immunity. DKK1 is over-expressed in gynecologic cancers and is associated with shortened survival. DKN-01 is a humanized monoclonal antibody with DKK1 neutralizing activity that may provide clinical benefit to patients whose tumors have overexpression of DKK1 or Wnt genetic alterations.

METHODS:

We conducted an open-label, Phase 2 basket study with 2-stage design in patients with endometrial carcinoma (EC) and platinum-resistant/refractory epithelial ovarian cancer. DKN-01 was administered either as monotherapy or in combination with weekly paclitaxel at investigator's discretion. All patients underwent NGS testing prior to enrollment; tumor tissue was also tested for DKK1 expression by RNAscope pre-treatment and after cycle 1 if available. At least 50% of patients were required to have a Wnt signaling alteration either directly or tangentially. This publication reports results from the EC population overall and by DKK1-expression.

RESULTS:

DKN-01 monotherapy and in combination with paclitaxel was more effective in patients with high DKK1-expressing tumors compared to low-expressing tumors. DKN-01 monotherapy demonstrated an objective response rate [ORR] of 25.0% vs. 0%; disease control rate [DCR] of 62.5% vs. 6.7%; median progression-free survival [PFS] was 4.3 vs. 1.8 months, and overall survival [OS] was 11.0 vs. 8.2 months in DKK1-high vs DKK1-low patients. Similarly, DKN-01 in combination with paclitaxel demonstrated greater clinical activity in patients with DKK1-high tumors compared to DKK1-low tumors: DCR was 55% vs. 44%; median PFS was 5.4 vs. 1.8 months; and OS was 19.1 vs. 10.1 months. Wnt activating mutations correlated with higher DKK1 expression. DKN-01 was well tolerated as a monotherapy and in combination with paclitaxel.

CONCLUSIONS:

Collectively, data demonstrates promising clinical activity of a well-tolerated drug, DKN-01, in EC patients with high tumoral DKK1 expression which frequently corresponded to the presence of a Wnt activating mutation. Future development will focus on using DKN-01 in DKK1-high EC patients in combination with immunotherapy.

News (Medical) associated with Sirexatamab

16 hours ago

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Leap Therapeutics Announces Closing of $58.88 Million Private Placement in Cash Led by Winklevoss Capital to Initiate a Digital Asset Treasury Strategy

CAMBRIDGE, Mass., Oct. 9, 2025 /PRNewswire/ -- Leap Therapeutics (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today announced that it has closed its previously announced private placement led by Winklevoss Capital raising $58,888,888 in cash to initiate a digital asset treasury strategy. At the closing of the transaction, Leap issued (i) 15,212,311 shares of common stock (the "Shares"), (ii) pre-funded warrants (the "Pre-Funded Warrants") to purchase up to an aggregate of 80,768,504 shares of common stock, and (ii) warrants to purchase an additional 71,985,605 shares of common stock at an exercise price of $0.5335 per share (the "Warrants" and together with the Shares and the Pre-Funded Warrants, the "Units"). Winklevoss Capital will provide both capital and strategic support to help Leap structure and execute its digital asset treasury strategy. Leveraging the expertise of Winklevoss Capital, Leap aims to build long-term shareholder value through participation in digital assets. A portion of the capital will be used to continue development of Leap's therapeutic programs, including FL-501 and sirexatamab, which has recently completed a randomized controlled Phase 2 trial in patients with colorectal cancer that is being presented in a Mini Oral Session at the European Society for Medical Oncology (ESMO) Congress 2025 on October 19 in Berlin, Germany. Pursuant to a lead investor agreement, Leap has increased the size of its Board of Directors to 12 members, and Winklevoss Capital will have the right to nominate two individuals to Leap's Board of Directors, one of whom shall also be the chairperson of the Board. Leap expects to release additional updates regarding its treasury activities in the near-term. Parcrest acted as the placement agent in connection with the financing. Morgan, Lewis & Bockius LLP acted as legal advisor to Leap, and Cooley LLP acted as legal advisor to Winklevoss Capital. The offer and sale of the foregoing securities is being made in a private placement in reliance on an exemption from the registration requirement of the Securities Act of 1933, as amended (the "Securities Act"), pursuant to Section 4(a)(2) of the Securities Act and/or Regulation D promulgated thereunder, and applicable state securities laws. Accordingly, the securities offered in the private placement may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirement of the Securities Act and such applicable state securities laws. Concurrently with the execution of the securities purchase agreements, the Company and the investors entered into a registration rights agreement pursuant to which the Company has agreed to file a registration statement with the Securities and Exchange Commission (the "SEC") registering the resale by the purchasers participating in the offering of the Shares and the shares of common stock underlying the Pre-Funded Warrants and the Warrants. Any offering of the Company's common stock under the resale registration statement will only be made by means of a prospectus. This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. The private placement was conducted in accordance with applicable Nasdaq rules and was priced to satisfy the "Minimum Price" requirement (as defined in the Nasdaq rules). About Leap Therapeutics Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's pipeline includes sirexatamab (DKN-01), a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein and FL-501, a humanized monoclonal antibody targeting the growth and differentiation factor 15 (GDF-15) protein. Leap is initiating a digital asset treasury strategy following a $58.88 million investment led by Winklevoss Capital. For more information about Leap Therapeutics, visit or view our public filings with the SEC that are available via EDGAR at or via . About Winklevoss Capital Winklevoss Capital is an investment firm founded in 2012 by Cameron and Tyler Winklevoss that invests in frontier technologies. Forward Looking Statements This press release includes forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements generally can be identified by the use of words such as "anticipate," "expect," "plan," "could," "may," "will," "believe," "estimate," "forecast," "goal," "project," and other words of similar meaning. These forward-looking statements address various matters including statements relating to the anticipated benefits and timing of the completion of the proposed offering and related transactions, the intended use of proceeds from the offering, the assets to be held by the Company, the expected future market, price and liquidity of the digital assets the Company acquires, the macro and political conditions surrounding digital assets, the Company's plan for value creation and strategic advantages, market size and growth opportunities, regulatory conditions, competitive position and the interest of other corporations in similar business strategies, technological and market trends, future financial condition and performance and the expected financial impacts of the proposed transactions described herein. Each forward-looking statement contained in this press release is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others, the risk that the proposed transactions described herein may not be completed in a timely manner or at all; failure to realize the anticipated benefits of the transactions and the proposed digital asset treasury strategy; changes in business, market, financial, political and regulatory conditions; risks relating to the Company's operations and business, including the highly volatile nature of the price of cryptocurrencies; the risk that the price of the Company's common stock may be highly correlated to the price of the digital assets that it holds; risks related to increased competition in the industries in which the Company does and will operate; risks relating to significant legal, commercial, regulatory, and technical uncertainty regarding digital assets generally; risks relating to the treatment of crypto assets for U.S. and foreign tax purposes, as well as those risks and uncertainties identified in the Company's filings with the Securities and Exchange Commission. The forward-looking statements in this press release speak only as of the date of this document, and the Company undertakes no obligation to update or revise any of these statements. Contacts Douglas E. Onsi President & Chief Executive Officer Leap Therapeutics, Inc. 617-714-0360 [email protected] Matthew DeYoung Investor Relations Argot Partners 212-600-1902 [email protected] SOURCE Leap Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2

07 Oct 2025

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Clinical Breakthroughs Converge as Immunotherapy Market Surges Past $136 Billion

USA News Group News Commentary Issued on behalf of GT Biopharma, Inc. VANCOUVER, BC, Oct. 7, 2025 /PRNewswire/ -- USA News Group News Commentary – Major pharmaceutical companies are unveiling breakthrough cancer data at the European Society for Medical Oncology Congress taking place October 17-21 in Berlin[1], while the global cancer immunotherapy market reached $137.70 billion in 2024 and analysts project explosive growth toward $261.74 billion by 2033[2]. The timing reflects a critical inflection point as HHS doubled federal funding for its Childhood Cancer Data Initiative from $50 million to $100 million, while researchers discovered how cancer uses a hidden hormone to shield itself from immune attack[3]. Against this backdrop of scientific momentum and institutional capital deployment, clinical-stage immunotherapy developers including GT Biopharma, Inc. (NASDAQ: GTBP), Leap Therapeutics, Inc. (NASDAQ: LPTX), IO Biotech (NASDAQ: IOBT), Celcuity Inc. (NASDAQ: CELC), and MAIA Biotechnology, Inc. (NYSE-American: MAIA). With eight new oncology approvals issued from July through September[4] and regulatory agencies accelerating approval pathways through breakthrough therapy designations, institutional forecasters at Precedence Research project the market will expand at a 10.65% CAGR through 2034[5] as long-term survival data validates immunotherapy durability. The convergence of rising disease burden, proven efficacy across cancer types, and expanded federal research support creates favorable conditions for early-positioned companies with differentiated mechanisms advancing through clinical milestones before broader institutional recognition materializes. GT Biopharma, Inc. (NASDAQ: GTBP) is a clinical-stage immunotherapy company making significant progress in its fight against difficult-to-treat cancers. The San Francisco-based biotech has been advancing its lead drug candidate, GTB-3650, through a Phase 1 clinical trial targeting blood cancers that have stopped responding to other treatments. In August, the company successfully moved into Cohort 3 after formal safety reviews of the first two patient groups showed no safety or tolerability problems. The trial had treated five patients by mid-August, with encouraging early signals of immune system activation. "We are pleased with the enrollment momentum in our Phase 1 clinical trial evaluating GTB-3650 in cancer patients, which continues to advance on schedule," said Michael Breen, Executive Chairman and Chief Executive Officer of GT Biopharma. "Moving into the third dose cohort after a successful safety review and encouraging early evidence of immunological activity, mark important steps forward in the development of GTB-3650. We look forward to sharing more data later this year to reinforce the ability of our TriKE constructs to activate endogenous NK cells, and the potential for broader utility with other targets to treat solid tumors (GTB-5550) and autoimmune indications (GTB-7550)." The Phase 1 trial is testing GTB-3650 in patients with relapsed or refractory CD33-expressing blood cancers, including acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). These are patients whose cancers have come back or never responded to standard therapies. The drug works by activating the body's own natural killer cells to attack cancer cells. Patients receive the treatment through continuous infusions in two-week cycles, alternating two weeks on and two weeks off, for up to four months based on how well they're responding. What makes the early data particularly interesting is the biomarker evidence. Multiple blood tests from the first four patients showed measurable increases in natural killer cell activity and expansion. This suggests the drug is doing exactly what it was designed to do—wake up the immune system and direct it against cancer. GT Biopharma expects to release more detailed Phase 1 results later this year after completing additional dose cohorts. Beyond blood cancers, GT Biopharma has a second drug candidate moving toward the clinic. GTB-5550 targets a protein called B7H3 that appears in many different types of solid tumors, including breast, lung, ovarian, head and neck, pancreatic, bladder, and prostate cancers. The company expects to submit its application to start human testing of GTB-5550 during the fourth quarter of this year. Unlike many cancer immunotherapies that require lengthy hospital infusions, GTB-5550 is being developed as a simple injection that patients could potentially give themselves at home, similar to insulin shots. Both drug candidates are built on GT Biopharma's proprietary TriKE platform, which uses specialized antibody fragments originally discovered in camels and llamas. These molecules are smaller and more stable than traditional antibodies, allowing them to work more effectively. GT Biopharma holds an exclusive worldwide license from the University of Minnesota to develop and commercialize therapies using this technology. As of June 30, 2025, GT Biopharmareported cash and cash equivalents of approximately $5.3 million, which management expected would fund operations into the first quarter of 2026. CONTINUED… Read this and more news for GT Biopharma, Inc. at: Leap Therapeutics, Inc. (NASDAQ: LPTX) are set to present final clinical results from Part B of the DeFianCe study at the European Society for Medical Oncology (ESMO) Congress 2025, taking place October 17-21 in Berlin, Germany. The Phase 2 study evaluated sirexatamab (DKN-01), an anti-DKK1 monoclonal antibody, in combination with bevacizumab and chemotherapy compared to bevacizumab and chemotherapy alone in patients with advanced microsatellite stable colorectal cancer who received one prior systemic therapy for advanced disease. The final results will be presented in a Mini Oral Session on October 19, 2025 at 4:05 p.m. CEST, with the presentation providing detailed efficacy and safety data from the second-line treatment cohort. Leap Therapeutics' pipeline also includes FL-501, a humanized monoclonal antibody targeting the growth and differentiation factor 15 protein, as the company continues developing targeted and immuno-oncology therapeutics for solid tumor indications. IO Biotech (NASDAQ: IOBT) announced that the U.S. Food and Drug Administration has recommended against submitting a Biologics License Application based on data from the IOB-013 clinical trial, in which Cylembio plus pembrolizumab improved progression free survival but narrowly missed statistical significance. The company is implementing a restructuring that includes an approximate 50 percent reduction in full-time employees and expects to incur a non-recurring charge of between $1.0 million and $1.5 million in the third quarter of 2025. "We had a productive meeting with FDA; while this is not the outcome we had hoped for, we respect FDA's feedback and remain confident in the therapeutic potential of Cylembio," said Mai-Britt Zocca, PhD, CEO of IO Biotech. "We look forward to continuing the dialogue with FDA to align on the design for a potential new registrational study. Additionally, we plan to discuss the data from our IOB-013 study with European regulators and determine a path to submission in the EU." The company plans to design a new registrational study for Cylembio for the treatment of first-line patients with advanced melanoma and currently has capital to run its operations into the first quarter of 2026. IO Biotech is pursuing a pathway to regulatory approval while working to complete ongoing studies of its immune-modulatory, off-the-shelf therapeutic cancer vaccine candidate. Celcuity Inc. (NASDAQ: CELC) will present detailed efficacy and safety data from the PIK3CA wild-type cohort of the pivotal Phase 3 VIKTORIA-1 trial at the European Society of Medical Oncology Congress 2025 in Berlin, Germany. The late breaking abstract has been selected for an oral presentation on October 18, 2025 at 10:15 a.m. CEST in a Proffered Paper Session, with the presentation covering results from gedatolisib plus fulvestrant with or without palbociclib versus fulvestrant in patients with HR+/HER2-/PIK3CA wildtype advanced breast cancer. The VIKTORIA-1 trial has completed enrollment and reported topline data for the PIK3CA wild-type cohort, while the company continues enrolling patients for the PIK3CA mutant cohort. Celcuity is also conducting its VIKTORIA-2 Phase 3 trial evaluating gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for HR+/HER2- advanced breast cancer, along with a Phase 1/2 trial combining gedatolisib with darolutamide in metastatic castration resistant prostate cancer patients. MAIA Biotechnology, Inc. (NYSE American: MAIA) has been awarded a $2.3 million grant by the National Institutes of Health for the expansion of its THIO-101 Phase 2 clinical trial evaluating ateganosine as a third-line treatment for patients with advanced non-small cell lung cancer. The grant, to be distributed over three years from 2025-2027, will support expenses related to enrollment of U.S. patients who are resistant to chemotherapy and immunotherapy, with Parts A and B of THIO-101 demonstrating median overall survival of 17.8 months for 22 patients in third-line treatment compared to 5 to 6 months for standard-of-care chemotherapy treatments. "We are thrilled to receive this prestigious NIH grant for the expansion of our Phase 2 trial," said Vlad Vitoc, M.D., CEO of MAIA Biotechnology. "It's a great honor to have the support of the National Institutes of Health as we seek to further validate the efficacy of our lead agent ateganosine and its potential to be a breakthrough treatment within the vastly underserved NSCLC market. With the clearance of FDA Investigational New Drug (IND) for THIO-101 in 2023, we can begin enrolling U.S. patients in the expansion phase of the trial immediately." The first patient in the expansion of the trial was dosed in July 2025 in Taiwan, with the NIH grant enabling MAIA to access a substantially larger patient pool across multiple continents. Ateganosine is a first-in-class investigational telomere-targeting agent that induces telomerase-dependent telomeric DNA modification and activates both innate and adaptive immune responses, currently being developed as a second or later line of treatment for NSCLC patients who have progressed beyond standard-of-care checkpoint inhibitor regimens. Article Sources: CONTACT: USA NEWS GROUP [email protected] (604) 265-2873 DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. This article is being distributed by USA News Group on behalf of Market IQ Media Group Inc. ("MIQ"). MIQ has been paid a fee for GT Biopharma, Inc. advertising and digital media from Creative Digital Media Group ("CDMG"). There may be 3rd parties who may have shares of GT Biopharma, Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ/BAY does not own any shares of GT Biopharma, Inc. but reserve the right to buy and sell, and will buy and sell shares of GT Biopharma, Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved on behalf of GT Biopharma, Inc. by CDMG; this is a paid advertisement, we currently own shares of GT Biopharma, Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. SOURCES: 1. 2. 3. 4. 5. Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultImmunotherapyPhase 3Phase 2Phase 1

25 Sep 2025

·www.prnewswire.com

Leap Therapeutics to Present Final Clinical Data from Part B of the DeFianCe Study at the ESMO Congress 2025

CAMBRIDGE, Mass., Sept. 25, 2025 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today announced it will present the final clinical results from Part B of the DeFianCe study (NCT05480306), a Phase 2 study of sirexatamab (DKN-01), an anti-DKK1 monoclonal antibody, in combination with bevacizumab and chemotherapy (Sirexatamab Arm) compared to bevacizumab and chemotherapy (Control Arm) in patients with advanced microsatellite stable (MSS) colorectal cancer (CRC) who have received one prior systemic therapy for advanced disease. The final results will be presented in a Mini Oral Session at the European Society for Medical Oncology (ESMO) Congress 2025, taking place October 17-21 in Berlin, Germany. Mini Oral Session Details: Title: DeFianCe Trial: A randomized phase 2 trial of sirexatamab (DKN-01) plus bevacizumab and chemotherapy versus bevacizumab and chemotherapy as second-line therapy in advanced microsatellite stable (MSS) colorectal cancer (CRC) Presenter: Zev A. Wainberg, M.D., Professor of Medicine and Co-Director of the GI Oncology Program at UCLA Session Type: Mini Oral Session Session Category: GI Tumours, Lower Digestive Date and Time: Sunday, October 19, 2025, 4:05 p.m. CEST Location: Cologne Auditorium – CityCube A Abstract Number: LBA34 About Leap Therapeutics Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's pipeline includes sirexatamab (DKN-01), a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein, and FL-501, a humanized monoclonal antibody targeting the growth and differentiation factor 15 (GDF-15) protein. For more information about Leap Therapeutics, visit or view our public filings with the SEC that are available via EDGAR at or via . FORWARD-LOOKING STATEMENTS This press release contains forward-looking statements within the meaning of the federal securities laws. Such statements are based upon current plans, estimates and expectations of the management of Leap that are subject to various risks and uncertainties that could cause actual results to differ materially from such statements. The inclusion of forward-looking statements should not be regarded as a representation that such plans, estimates and expectations will be achieved. Words such as "anticipate," "expect," "project," "intend," "believe," "may," "will," "should," "plan," "could," "continue," "target," "contemplate," "estimate," "forecast," "guidance," "predict," "possible," "potential," "pursue," "likely," and words and terms of similar substance used in connection with any discussion of future plans, actions or events identify forward-looking statements. All statements, other than historical facts, including statements regarding the potential safety, efficacy, and regulatory and clinical progress of Leap's product candidates, including sirexatamab and FL-501; Leap's plan to reduce clinical and operational activities, reduce spending and conserve cash, explore strategic alternatives to preserve and maximize shareholder value, including by leveraging its cash balance and potentially selling or partnering sirexatamab or FL-501; and any assumptions underlying any of the foregoing, are forward-looking statements. Important factors that could cause actual results to differ materially from Leap's plans, estimates or expectations could include, but are not limited to: (i) Leap's ability to successfully sell or enter into partnerships for sirexatamab or FL-501; (ii) the cost and timeline to complete the DeFianCe Study and wind-down operations; (iii) any regulatory feedback that Leap may receive from U.S. Food and Drug Administration (FDA) or equivalent foreign regulatory agency or from site institutional review boards; and (iv) the availability of strategic alternatives that would preserve or generate any shareholder value. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Leap may not actually achieve the forecasts disclosed in such forward-looking statements, and you should not place undue reliance on such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Leap's most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in its subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither Leap, nor any of its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing Leap's views as of any date subsequent to the date hereof. CONTACT: Douglas E. Onsi President & Chief Executive Officer Leap Therapeutics, Inc. 617-714-0360 [email protected] Matthew DeYoung Investor Relations Argot Partners 212-600-1902 [email protected] SOURCE Leap Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Clinical ResultImmunotherapy

100 Deals associated with Sirexatamab

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Adenocarcinoma of large intestine	Phase 2	United States	Leap Therapeutics, Inc.	30 Aug 2022
Adenocarcinoma of large intestine	Phase 2	Germany	Leap Therapeutics, Inc.	30 Aug 2022
Adenocarcinoma of large intestine	Phase 2	South Korea	Leap Therapeutics, Inc.	30 Aug 2022
Advanced Colorectal Adenocarcinoma	Phase 2	United States	Leap Therapeutics, Inc.	30 Aug 2022
Advanced Colorectal Adenocarcinoma	Phase 2	Germany	Leap Therapeutics, Inc.	30 Aug 2022
Advanced Colorectal Adenocarcinoma	Phase 2	South Korea	Leap Therapeutics, Inc.	30 Aug 2022
Gastroesophageal junction adenocarcinoma	Phase 2	United States	BeOne Medicines Ltd.	29 Jul 2020
Gastroesophageal junction adenocarcinoma	Phase 2	United States	Leap Therapeutics, Inc.	29 Jul 2020
Gastroesophageal junction adenocarcinoma	Phase 2	Germany	BeOne Medicines Ltd.	29 Jul 2020
Gastroesophageal junction adenocarcinoma	Phase 2	Germany	Leap Therapeutics, Inc.	29 Jul 2020

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04363801 (DisTinGuish, Pubmed) Manual	Phase 2	Gastroesophageal junction adenocarcinoma Second line DKK1 Expression	52	DKN-01+tislelizumab	brsbvdmjxk(ioucizvewb) = dyhuztvjni oxrbnvhdgl (kvbsnffdvz ) Met View more	Positive	10 Jul 2025
NCT05480306 (DeFianCe, Company_Website) Manual	Phase 2	Colorectal Cancer Second line DKK1 Expression \| Microsatellite Stable (MSS)	188	Sirexatamab + bevacizumab + chemotherapy (high DKK1 levels)	prpbwmyzsc(ahpfptcqpm) = vtjrkxrgri zliwfgclbv (jijsdxmdop ) View more	Positive	26 Mar 2025
				bevacizumab + chemotherapy (high DKK1 levels)	prpbwmyzsc(ahpfptcqpm) = opmywpnlzc zliwfgclbv (jijsdxmdop ) View more
NCT05480306 (DeFianCe, PRNewswire) Manual	Phase 2	Microsatellite Stable Colorectal Carcinoma Second line Microsatellite Stable (MSS)	188	Sirexatamab + bevacizumab + chemotherapy	iupdccnftb(qlzfrfqrhe) = qohsjdbkkv icmxoldedp (fnneszizry ) View more	Positive	28 Jan 2025
				bevacizumab + chemotherapy	iupdccnftb(qlzfrfqrhe) = sidzdfours icmxoldedp (fnneszizry ) View more
NCT04363801 (DisTinGuish, PRNewswire) Manual	Phase 2	Gastrooesophageal junction cancer \| Advanced gastric carcinoma First line HER2 Negative	170	Sirexatamab + tislelizumab + chemotherapy	rfmhqwtlig(rdiorlqwck) = olecyfstmk jmgabifbun (kfceycoqal ) View more	Positive	28 Jan 2025
				Tislelizumab + chemotherapy	rfmhqwtlig(rdiorlqwck) = ssaaexmmcg jmgabifbun (kfceycoqal ) View more
NCT04363801 (DisTinGuish, Pubmed \| J Clin Oncol)	Phase 2	Advanced Gastroesophageal Junction Adenocarcinoma First line DKK1-high tumor \| DKK1-low tumor	25	DKN-01	smtbabrfxp(uymvzhvvvo) = xyhxbrbfak cwgpewvqrs (xzvdrnmlkg, 49.8 - 89.3) View more	Positive	21 Oct 2024
NCT05480306 (DeFianCe, NEWS) Manual	Phase 2	Microsatellite Stable Colorectal Carcinoma	33	DKN-01	xrrjnprnon(fbllambsdd) = dubxqwoqcr voxrandljd (hbwolesgga ) View more	Positive	03 Jun 2024
				DKN-01 (左结肠肿瘤)	xrrjnprnon(fbllambsdd) = edtjgxbjsc voxrandljd (hbwolesgga ) View more
NCT04057365 (CTgov)	Phase 2	Advanced Bile Duct Carcinoma	15	Nivolumab+DKN-01 (DKN 01 and Nivolumab Safety Run in)	ibqiedolga = tdsqaydisq vscfycfyms (moldkqdeoa, mdkupulpjw - yodzcgzzfy) View more	-	10 Apr 2024
				Nivolumab+DKN-01 (DKN 01 and Nivolumab)	lnoujownzg(kweekmofxo) = soxxkupmhg rbgkwxknfj (abxnpbwjzi, muyugakmxu - elgobndfgf) View more
NCT05480306 (DeFianCe, ASCO_GI2024) Manual	Phase 2	Microsatellite Stable Colorectal Carcinoma Second line Microsatellite Stable (MSS)	33	DKN-01 + FOLFIRI/FOLFOX + bevacizumab	ghcsibnrff(dhqvyolorg) = ywxvctovfg gaxzxvahhi (ydpmoyoopl ) View more	Positive	18 Jan 2024
NCT03837353 (CTgov)	Phase 1/2	Advanced Prostate Carcinoma	18	DKN-01+Docetaxel (Cohort 1A.1 (DKN-01 300mg, Docetaxel 75 mg/m2))	njwxmbnwfl(tsuyriigso) = wabcevsrbw qmazruuftj (taoyugqdzx, 0) View more	-	18 Dec 2023
				DKN-01+Docetaxel (Cohort 1A.2 (DKN-01 600mg, Docetaxel 75 mg/m2))	njwxmbnwfl(tsuyriigso) = hkidjepsln qmazruuftj (taoyugqdzx, 0) View more
NCT04363801 (DisTinGuish, ASCO 12023 \| ASCO 22023) Manual	Phase 2	Advanced Gastroesophageal Junction Adenocarcinoma First line	22	CAPOX+Tislelizumab+DKN 01 (ITT population)	lkaaybxfvv(rwcvhbdpbz) = hznhzgkkmn mhloeactti (ltyomgkeqc ) View more	Positive	26 May 2023
				CAPOX+Tislelizumab+DKN 01 (low tumor PD-L1 expression)	lkaaybxfvv(rwcvhbdpbz) = slradpubwx mhloeactti (ltyomgkeqc ) View more

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