Leap Therapeutics has come crashing down to earth. The biotech axed plans to advance into phase 3 in gastric cancer on the basis of midstage data, sending its stock down 60% to below $1, but it is forging ahead in another indication.
Massachusetts-based Leap made the decisions after seeing data from two parts of a phase 2b trial of its anti-DKK1 antibody sirexatamab. The biotech reported a 35% response rate in colorectal cancer patients who received sirexatamab, bevacizumab and chemotherapy, compared to 23% in the active control arm.
After an average of six months of follow-up, Leap saw signs of improved progression-free survival (PFS) in some subgroups. The signs are yet to translate into a statistically significant improvement in PFS and 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.
That is as good as it got for Leap. 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,” Cynthia Sirard, M.D., chief medical officer at Leap, said in a statement. The trial will be negative on the PFS endpoints when it completes, Leap said.
Based on the results, Leap decided to focus on colorectal cancer and drop plans to run a gastric cancer phase 3. Sirard said Leap 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.”
Leap CEO Douglas Onsi compared the colorectal and gastric opportunities at a Piper Sandler event last month, where he said “every single pharmaceutical company know[s] it is a very substantial U. S. and European market, and stands on its own.”
“Gastric cancer is important to some companies and not to others,” Onsi added at the December event. “I think people look at the gastric opportunity as a PD-1 combination opportunity and the opportunity to take it beyond gastric to other PD-1 combinations.”