Leap Therapeutics Shifts Focus to Colorectal Cancer as Gastric Cancer Program Falters

Leap Therapeutics, a Massachusetts-based biotech company, has announced significant changes to its clinical development strategy following mixed results from its phase 2b trial of sirexatamab, an anti-DKK1 antibody. The company's stock plummeted by 60% to below $1 as it revealed plans to discontinue its gastric cancer program while advancing efforts in colorectal cancer.

Promising Results in Colorectal Cancer

In the colorectal cancer arm of the study, sirexatamab demonstrated encouraging efficacy when combined with bevacizumab and chemotherapy. The experimental arm showed a 35% response rate, compared to 23% in the active control group. While progression-free survival (PFS) data are still maturing, Leap reported early signs of improvement in certain subgroups.

Dr. Cynthia Sirard, Chief Medical Officer at Leap, stated that these results support moving forward with a registrational phase 3 trial in second-line colorectal cancer patients. The company is currently analyzing subgroup data to determine the optimal patient population for the upcoming study.

Setback in Gastric Cancer Program

Contrary to the positive outcomes in colorectal cancer, the gastric cancer arm of the trial yielded disappointing results. The study evaluated sirexatamab in combination with BeiGene's anti-PD-1 antibody tislelizumab and chemotherapy in first-line advanced gastroesophageal junction and gastric cancer patients.

Despite improvements in confirmed response rates in the intent-to-treat population and PD-L1 negative subgroups, as assessed by blinded independent central review (BICR), Dr. Sirard noted a "high level of discordance between investigator assessment and BICR." Leap anticipates that the trial will fail to meet its PFS endpoints upon completion, leading to the decision to abandon plans for a phase 3 gastric cancer study.

Strategic Pivot and Future Directions

Leap Therapeutics CEO Douglas Onsi emphasized the company's strategic shift during a recent Piper Sandler event. He highlighted the substantial market opportunity for colorectal cancer treatments in the United States and Europe, contrasting it with the more niche appeal of gastric cancer therapies.

While discontinuing its own gastric cancer program, Leap remains open to potential partnerships to advance sirexatamab in combination with anti-PD-1 antibodies for gastric cancer and other indications with high DKK1 expression. This approach allows the company to maintain a presence in the gastric cancer space while focusing its internal resources on the more promising colorectal cancer opportunity.

As Leap Therapeutics navigates this pivotal moment, the biopharmaceutical industry will be watching closely to see how the company's renewed focus on colorectal cancer unfolds and whether strategic partnerships materialize to keep its gastric cancer research alive.