Leap Therapeutics to Present Updated Data from the DisTinGuish Study of DKN-01 Plus Tislelizumab and Preclinical Data in Colorectal Cancer Models at the SITC Annual Meeting
55% ORR, 73% DCR, and 7.7 month PFS in
DKN-01 also demonstrated preclinical tumor regression data in CRC models supporting ongoing clinical trial
Leap is also presenting preclinical DKN-01 data supporting the DeFianCe study, a Phase 2 study of DKN-01 in combination with bevacizumab and standard of care chemotherapy in patients with advanced colorectal cancer (CRC) who have received one prior systemic therapy.
"The combination of DKN-01 plus tislelizumab continues to demonstrate a well-tolerated and active combination in previously treated,
"The preclinical results in CRC models showed impressive monotherapy and chemotherapy combination activity in multiple xenograft models, including those that are resistant to 5-FU treatment, which is commonly used to treat metastatic disease," said
Key Findings DisTinGuish
- DKN-01 and tislelizumab administered in
DKK1 -high (H-score > 35), PD-1 naïve patients were well tolerated at both 300mg and 600mg DKN-01 doses - Higher DKN-01 dose at 600mg was not associated with higher frequency of adverse events (AEs)
- There were no Grade 5 treatment-emergent AEs (TEAE) and no TEAEs leading to study drug discontinuation or dose reduction
- High and durable 27% overall response rate (ORR) in evaluable anti-PD-1/PD-L1 naïve mITT population (n=43)
- 55% ORR, 73% disease control rate, and 7.7 months median progression-free survival in
DKK1 -high/PD-L1-high vCPS ≥ 10 patients (n=12: 6 PR, 2 SD, 3 PD, 1 NE) - 27% ORR in
DKK1 -high/PD-L1-negative vCPS < 1 patients (n=11: 3 PR, 1 SD, 7 PD) - Overall, 7 of 10 responders remain on therapy
Key Findings Preclinical CRC
- DKN-01 showed additive activity with 5-fluorouracil (5-FU) and can overcome 5-FU-resistance in
two CRC xenograft models, resulting in tumor regressions - 5-FU-resistant models are reflective of a second-line CRC population currently being recruited in the DeFianCe study (NCT05480306)
- DKN-01 as monotherapy or in combination with anti-PD-1 resulted in tumor regression in a CT26 syngeneic CRC model
- Treatment increased PD-L1 immunoreactivity
- Promoted substantial tumor necrosis which was associated with a robust immune cell infiltrate
- Tumor immune infiltrate contained a substantial number of CD3+ and CD8+ cells, implying the presence of an adaptive immune response to tumor antigen
Leap Poster Details:
Title: DKN-01 and Tislelizumab as a Second-line (2L) Investigational Therapy in Advanced
First Author: Samuel
Session Category: Poster Session
Session title: Immune-stimulants and immune modulators
Date and time:
Poster Number: 553
Title: DKN-01 Demonstrates Immune Modulatory Activity and Robust Efficacy in Colorectal Cancer Models
First Author:
Session Category: Poster Session
Session title: Immune-stimulants and immune modulators
Date and time:
Poster Number: 1141
About the DisTinGuish Study
The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab, an anti-PD-1 antibody, with or without chemotherapy as first-line or second-line therapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. The study is being conducted in three parts in
About the DeFianCe Study
The DeFianCe study (NCT05480306) is a Phase 2, randomized, open-label, multicenter study of DKN-01 in combination with standard of care bevacizumab and chemotherapy in patients with advanced CRC who have received one prior systemic therapy. The study is designed with an initial 20 patient cohort and to then expand into a 130-patient randomized controlled trial against bevacizumab and standard of care chemotherapy.
About
FORWARD-LOOKING STATEMENTS
This press release contains 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, and the Private Securities Litigation Reform Act of 1995, which involve risks and uncertainties. These statements include Leap's expectations with respect to the development and advancement of DKN-01, including the initiation, timing and design of future studies, enrollment in clinical studies, potential for the receipt of future option exercise, milestone, or royalty payments from BeiGene, and other future expectations, plans and prospects. Although Leap believes that the expectations reflected in such forward-looking statements are reasonable as of the date made, forward-looking statements are subject to known and unknown risks, uncertainties and other factors that could cause actual results to differ materially from our expectations. Such risks and uncertainties include, but are not limited to: that the initiation, conduct, and completion of clinical trials, laboratory operations, manufacturing campaigns, and other studies may be delayed, adversely affected, or impacted by COVID-19, global conflict or supply chain related issues; unstable global market and economic conditions; the accuracy of our estimates regarding expenses, future revenues, capital requirements and needs for financing; the outcome, cost, and timing of our product development activities and clinical trials; the uncertain clinical development process, including the risk that clinical trials may not have an effective design or generate positive results; our ability to obtain and maintain regulatory approval of our drug product candidates; the size and growth potential of the markets for our drug product candidates; our ability to continue obtaining and maintaining intellectual property protection for our drug product candidates; and other risks. Detailed information regarding factors that may cause actual results to differ materially is included in
CONTACT:
President & Chief Executive Officer
617-714-0360
donsi@leaptx.com
Investor Relations
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