Full Press Release Details
Leap Therapeutics Reports Initial Clinical
Data from Part B of the DeFianCe Study and
Part C of the DisTinGuish Study
35% objective response rate (ORR) in second-line
colorectal cancer (CRC) patients treated with sirexatamab (DKN-01) plus bevacizumab and chemotherapy, compared to 23% ORR in the control
DKK1 levels highly correlated with clinical
activity in CRC population
ORR benefit with sirexatamab observed across
multiple potential Phase 3 CRC populations
Preparations will begin for a registrational
Phase 3 study in second-line CRC patients
DisTinGuish Part C study in gastric cancer
demonstrates activity in biomarker populations,
but not the signal necessary to advance into
Leap to host a conference call to present clinical
data today, January 28, 2025, at 8:00 a.m. ET
Cambridge, MA - January 28, 2025
- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics,
today announced positive initial data from Part B of the DeFianCe study evaluating sirexatamab (DKN-01) in combination with bevacizumab
and chemotherapy as a second-line treatment for patients with advanced colorectal cancer (CRC), and initial data from Part C of the DisTinGuish
study evaluating sirexatamab in combination with tislelizumab and chemotherapy in first-line patients with advanced gastroesophageal
junction (GEJ) and gastric cancer.
Key Findings from Part B of the
"Data from Part B of the DeFianCe study
closely mirror the findings from Part A, and together they demonstrate the potential of sirexatamab to provide a compelling treatment
option for second-line CRC patients who do not benefit from current standard of care," said Cynthia Sirard, M.D., Chief Medical
Officer of Leap. "Along with consistently achieving higher response rates than the control arm, the data also point to a favorable
safety profile. While not yet fully mature, we are encouraged by the progression-free survival data thus far across key subgroups in
the study. We look forward to reporting additional data from Part B as it matures over the coming months and beginning our planning for
Phase 3 registrational studies."
"The patient population in second-line
CRC is heterogeneous, and there is a true unmet need for new treatment options that are safe and effective. The latest findings from
DeFianCe Part B are highly encouraging, as sirexatamab combination therapy is outperforming bevacizumab and chemotherapy alone in ORR
in the intent-to-treat analysis and across key subgroups of interest," said Zev Wainberg, M.D., Professor of Medicine and Co-Director
of the GI Oncology Program at UCLA. "Initial results also show increased response rates in patients with high DKK1 levels, directly
correlating with sirexatamab's novel mechanism of action. These data support moving forward into Phase 3 registrational studies
to further explore a unique treatment option for patients in need."
The DeFianCe study (NCT05480306)
is a Phase 2, open-label, global study of sirexatamab in combination with bevacizumab and chemotherapy in patients with advanced microsatellite
stable (MSS) CRC who have received one prior systemic therapy for advanced disease. Part B of the study is a 188 patient randomized controlled
trial, with the primary objective being progression-free survival (PFS) in patients with left-sided cancers and in all patients. Key
secondary and exploratory objectives include objective response rate (ORR), duration of response, and overall survival across tumor,
treatment, and biomarker subgroups.
The strong signal in CRC from the DeFianCe study
supports Leap moving forward to plan a registrational Phase 3 clinical trial to evaluate sirexatamab plus bevacizumab and chemotherapy
in second-line MSS CRC patients with high unmet need, subject to regulatory discussions. Potential Phase 3 patient populations include:
DKK1 biomarker-selected, anti-VEGF na ve, anti-EGFR experienced, or RAS-wt patients. While the data matures, Leap intends to conduct
global commercial and regulatory strategic analysis to select the optimal population.
Key Findings from Part C of the DisTinGuish
Leap also reported data from Part C of the DisTinGuish
study evaluating sirexatamab in combination with tislelizumab, BeiGene's anti-PD-1 antibody, and chemotherapy in first-line patients
with advanced GEJ and gastric cancer. While demonstrating activity in biomarker populations, the study did not generate a clear positive
signal and will be negative on the primary PFS endpoints when the study completes, resulting in the decision not to move forward with
Phase 3 studies in gastric cancer.
"Sirexatamab plus tislelizumab and chemotherapy
demonstrated improved confirmed response rates compared to the control arm in the ITT, DKK1-high, and PD-L1 negative patients by Blinded
Independent Central Review (BICR). However, gastric cancer is a difficult tumor to assess radiologically, and unfortunately, there was
a high level of discordance between investigator assessment (IA) and BICR," said Dr. Sirard. "Therefore, we have decided
to focus our internal effort and resources on advancing sirexatamab in CRC and will explore strategic partnership opportunities to advance
sirexatamab plus anti-PD-1 antibodies in gastric cancer and other indications where there is high DKK1 expression."
Part C of the DisTinGuish study (NCT0436380)
is a Phase 2, randomized, open-label, multicenter study of sirexatamab in combination with tislelizumab and chemotherapy in first-line
patients with advanced GEJ and gastric cancer. Part C enrolled 170 first-line, HER2-negative patients. Patients were randomized 1:1 to
evaluate sirexatamab in combination with tislelizumab and chemotherapy, compared to tislelizumab and chemotherapy alone. The primary
objective is PFS by IA in all patients and in DKK1 TPS > 20 (DKK1-high) patients. Secondary objectives include ORR, duration
of response, and overall survival as measured by BICR and IA in all patients and in DKK1-high patients.
Leap's management team will host a conference
call today, January 28, 2025 at 8:00 a.m. Eastern Time to further discuss the data. The conference call will be broadcast live in listen-only
mode and can be accessed via the webcast URL: https://edge.media-server.com/mmc/p/t93pn2ke. A replay of the event will
be available for a limited time on the Investors page of the Company's website at https://investors.leaptx.com/.
About Leap Therapeutics
Leap Therapeutics (Nasdaq: LPTX) is focused
on developing targeted and immuno-oncology therapeutics. Leap's most advanced clinical candidate, sirexatamab (DKN-01), is a humanized
monoclonal antibody targeting the Dickkopf-1 (DKK1) protein. Sirexatamab is being studied in patients with colorectal, esophagogastric,
and gynecological cancers. Leap's pipeline also includes FL-501, a humanized monoclonal antibody targeting the growth and differentiation
factor 15 (GDF-15) protein, in preclinical development. For more information about Leap Therapeutics, visit http://www.leaptx.com or
view our public filings with the SEC that are available via EDGAR at http://www.sec.gov or via https://investors.leaptx.com/.
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; the
anticipated timing for initiation or completion of clinical trials and release of clinical trial data and the expectations surrounding
the outcomes thereof; Leap's future clinical or preclinical product development plans for any of Leap's product candidates; Leap's estimations
of projected cash runway; 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)
the results of Leap's clinical trials and pre-clinical studies, including whether the final data from Part B of the DeFianCe study or
Part C of the DisTinGuish study are the same as the initial data reported, (ii) Leap's ability to successfully finance or enter into
new strategic partnerships for sirexatamab or any of its other programs; (iii) any regulatory feedback that Leap may receive from U.S.
Food and Drug Administration (FDA) or equivalent foreign regulatory agency with respect to the registrational Phase III clinical
trials that Leap proposes to conduct using sirexatamab for the treatment of patients with second-line CRC or with respect to any other
pre-clinical or clinical development activities that Leap will be required to conduct in order to obtain regulatory approval of sirexatamab
for the treatment of second-line CRC; (iv) whether any Leap products will receive approval from the FDA or equivalent foreign