Leap Therapeutics Halts Sirexatamab Combo Therapy for Gastric Cancer Amid Unclear Positive Signal, Stock Crashes

Leap Therapeutics, Inc. (LPTX) has announced its decision to halt the development of sirexatamab in combination with tislelizumab for gastric cancer, despite initial positive signals. The biotech company's stock price has crashed, falling by 78.80% to $0.66 at last check on Tuesday, January 28, 2025. The move comes after Leap reviewed midstage data from a phase 2b trial of its anti-DKK1 antibody sirexatamab.

Leap reported a 35% response rate in colorectal cancer patients who received sirexatamab, bevacizumab, and chemotherapy, compared to 23% in the active control arm. However, the company saw signs of improved progression-free survival (PFS) in some subgroups, but these signs have not yet translated into a statistically significant improvement in PFS. The number of PFS events is evenly balanced between the experimental and control arms, with 37 and 38, respectively. More people, 46, are still on the study drug than the control, 36.



Leap said the "strong signal" supports taking the drug combination into a registrational phase 3 trial in second-line patients. The biotech saw higher response rates in some subgroups and will decide on the optimal population for the phase 3 as the data mature. However, the company decided to focus on colorectal cancer and drop plans to run a gastric cancer phase 3 trial after reviewing the data from the other part of the study.

The other part of the study assessed the effect of adding sirexatamab to tislelizumab, BeiGene's anti-PD-1 antibody, and chemotherapy in first-line advanced gastroesophageal junction and gastric cancer patients. The combination improved confirmed response rates in the intent-to-treat population and subgroups of PD-L1 negative patients by blinded independent central review (BICR). However, there was a high level of discordance between investigator assessment and BICR, leading Leap to decide not to move forward with Phase 3 studies in gastric cancer.



Leap Therapeutics' decision to focus on colorectal cancer and drop plans for a gastric cancer phase 3 trial has significant implications for the company's financial outlook and market position in the biotech sector. The company's stock price has been volatile, with a 78.80% decrease to $0.66 at last check on Tuesday, January 28, 2025. The company's focus shift and the potential for a successful Phase 3 trial in CRC could lead to improved investor confidence and a potential rebound in stock price.

Leap's ability to successfully complete the Phase 3 trial in CRC and obtain regulatory approval for sirexatamab will be crucial for the company's financial outlook and market position. Positive clinical data and regulatory approval could lead to increased revenue and market share, while setbacks could negatively impact the company's financial outlook and market position.