On June 23, 2025 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported updated 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 (Press release, Leap Therapeutics, JUN 23, 2025, View Source [SID1234654056]). Due to the Company’s financial position, Leap’s Board of Directors is taking further steps to preserve capital and has initiated a process to explore strategic options to preserve and maximize shareholder value.
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"Sirexatamab demonstrated a statistically significant benefit in patients with high levels of DKK1, no prior exposure to anti-VEGF therapy, or liver metastasis, with a positive trend on ORR and PFS in the full second-line CRC population. With the additional patient follow-up, we believe that the objectives of the DeFianCe study have been achieved. On behalf of everyone at Leap, I thank all the patients and physicians who have participated in our sirexatamab clinical trials," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "However, due to current market conditions, we have decided to wind-down the DeFianCe clinical trial and further reduce internal expenses. In parallel, we have initiated a review of the full range of strategic alternatives to maximize shareholder value."
DeFianCe Study Update
In the updated analysis as of May 22, 2025, sirexatamab demonstrated a positive trend on overall response rate (ORR), by investigator assessment (IA) and blinded independent central review (BICR), and progression-free survival (PFS) in the full second-line CRC population, driven by the statistically significant benefit in patients with high levels of DKK1, no prior exposure to anti-VEGF therapy, or liver metastasis.
· Across the intent-to-treat population (n=188):
Sirexatamab Arm
(n=94) Control Arm
(n=94)
Median PFS 9.2 months 8.31 months HR 0.84
95% CI: 0.57, 1.22
p = 0.1749
ORR by IA 35.1% 26.6% p = 0.1009
ORR by BICR 33.0% 20.2% P = 0.0203
Remaining on study drug 21 15
· In patients with high DKK1 levels (upper quartile, n=44):
Sirexatamab Arm
(n=25) Control Arm
(n=19)
Median PFS 9.36 months 5.88 months HR 0.47
95% CI: 0.22, 1.01
p = 0.0237
ORR by IA 44.0% 15.8% p = 0.0149
ORR by BICR 40.0% 15.8% p = 0.0301
Median OS Not Yet Reached 9.66 months HR 0.19
95% CI: 0.05, 0.73
p = 0.0037
Remaining on study drug 7 1
· In patients with DKK1 levels above the median (upper median, n=88):
Sirexatamab Arm
(n=50) Control Arm
(n=38)
Median PFS 9.03 months 7.23 months HR 0.56
95% CI: 0.33, 0.94
p = 0.0146
ORR by IA 38.0% 23.7% p = 0.0706
ORR by BICR 40.0% 15.8% p = 0.0039
Median OS Not Yet Reached 14.39 months HR 0.48
95% CI: 0.2, 1.16
p = 0.0475
Remaining on study drug 12 3
· In patients who had not received prior anti-VEGF therapy (n=95):
Sirexatamab Arm
(n=49) Control Arm
(n=46)
Median PFS 11.2 months 8.34 months HR 0.61
95% CI: 0.35, 1.06
p = 0.0383
ORR by IA 55.1% 32.6% p = 0.0116
ORR by BICR 44.9% 26.1% p = 0.0252
Median OS Not Yet Reached Not Yet Reached HR 0.47
95% CI: 0.14, 1.6
p = 0.1069
Remaining on study drug 15 5
· In patients with liver metastases (n=138):
Sirexatamab Arm
(n=73) Control Arm
(n=65)
Median PFS 9.03 months 7.26 months HR 0.7
95% CI: 0.46, 1.06
p = 0.0443
ORR by IA 37.0% 27.7% p = 0.1203
ORR by BICR 30.1% 24.6% p = 0.233
Median OS Not Yet Reached 15.74 HR 0.69
95% CI: 0.33, 1.43
p = 0.1584
Remaining on study drug 14 6
Corporate Update
Leap is taking additional steps to reduce spending and preserve capital. Over the next two months as the DeFianCe study completes, the Company will implement a workforce reduction of approximately 75%. The total cash payments and costs related to this reduction in force, including severance payments, are estimated to be approximately $3.2 million. The majority of these costs will be recognized in the third quarter of 2025. The Company’s cash and cash equivalents totaled $32.7 million as of March 31, 2025.
Leap has initiated a process to explore strategic alternatives to preserve and maximize shareholder value, including leveraging its cash balance and exploring potential sale or partnership opportunities for sirexatamab and FL-501. The Company’s Board of Directors has approved the engagement of Raymond James & Associates, Inc. to serve as exclusive financial advisor to assist in the strategic evaluation process.