8-K: Leap Therapeutics Announces Positive Colorectal Cancer Data, Shifts Focus from Gastric Cancer

Leap Therapeutics reported a 35% objective response rate in second-line colorectal cancer patients treated with sirexatamab, while a gastric cancer study did not show sufficient benefit to advance to Phase 3.

Summary

• Leap Therapeutics announced initial clinical data from two studies: DeFianCe (colorectal cancer) and DisTinGuish (gastric cancer).
• The DeFianCe study showed a 35% objective response rate (ORR) in second-line colorectal cancer (CRC) patients treated with sirexatamab plus bevacizumab and chemotherapy, compared to 23% in the control arm.
• The DeFianCe study also showed that DKK1 levels are highly correlated with clinical activity in CRC patients, with higher ORRs observed in patients with elevated DKK1.
• The DisTinGuish study in gastric cancer demonstrated activity in biomarker populations, but did not show a clear positive signal to advance into Phase 3.
• Leap will now prioritize a Phase 3 registrational study in second-line CRC and explore strategic partnerships for gastric cancer.

Sentiment

Score: 7

Explanation: The sentiment is positive due to the promising results in colorectal cancer, but tempered by the decision not to proceed with Phase 3 in gastric cancer. The focus on a larger market opportunity and the potential for strategic partnerships are viewed favorably.

Positives

• The DeFianCe study demonstrated a significant improvement in ORR for second-line CRC patients with the addition of sirexatamab.
• The correlation between DKK1 levels and clinical activity in the DeFianCe study suggests a potential biomarker for patient selection.
• Sirexatamab was well-tolerated in both studies, without additive toxicity to the standard of care.
• The DisTinGuish study showed activity in biomarker populations, indicating potential for sirexatamab in gastric cancer with strategic partnerships.
• Leap is prioritizing the larger market opportunity in CRC with a clear path to Phase 3 development.

Negatives

• The DisTinGuish study in gastric cancer did not generate a clear positive signal to advance into Phase 3.
• There was a high level of discordance between investigator assessment and Blinded Independent Central Review (BICR) in the DisTinGuish study.
• The DisTinGuish study will be negative on the primary PFS endpoints when the study completes.
• The median PFS in the DisTinGuish study was not improved in the experimental arm compared to the control arm.

Risks

• The final data from the DeFianCe study may differ from the initial data reported.
• Leap's ability to successfully finance or enter into new strategic partnerships for sirexatamab is uncertain.
• Regulatory feedback from the FDA or equivalent agencies could impact the Phase 3 clinical trials.
• There is a risk that Leap products may not receive approval from the FDA or equivalent agencies.
• Exposure to inflation and interest rate fluctuations, as well as fluctuations in the market price of Leap's traded securities, could impact the company.

Future Outlook

Leap plans to begin preparations for a Phase 3 registrational study in second-line colorectal cancer patients 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.

Management Comments

• Cynthia Sirard, M.D., Chief Medical Officer of Leap, stated that the data from Part B of the DeFianCe study closely mirror the findings from Part A, demonstrating the potential of sirexatamab as a treatment option for second-line CRC patients.
• Zev Wainberg, M.D., Professor of Medicine at UCLA, noted that the findings from DeFianCe Part B are highly encouraging, as sirexatamab combination therapy is outperforming bevacizumab and chemotherapy alone in ORR.
• Dr. Sirard also mentioned that while the DisTinGuish study demonstrated activity in biomarker populations, it did not generate a clear positive signal, leading to the decision not to move forward with Phase 3 studies in gastric cancer.

Industry Context

The announcement is significant as it highlights the potential of sirexatamab in colorectal cancer, a disease with a high unmet need for new treatment options. The shift in focus from gastric cancer to colorectal cancer reflects a strategic decision based on the clinical data and market opportunity. The results are being compared to existing treatments such as bevacizumab and chemotherapy.

Comparison to Industry Standards

• The DeFianCe study's control arm, using bevacizumab and chemotherapy, achieved a 23% ORR, which is consistent with historical data for second-line colorectal cancer treatments.
• The experimental arm in the DeFianCe study, with sirexatamab added, achieved a 35% ORR, demonstrating a significant improvement over the standard of care.
• The DisTinGuish study's control arm, using tislelizumab and chemotherapy, had a median PFS of 11.99 months by BICR and 10.41 months by IA, which is higher than the 6.9 months reported in the Rationale-305 study for tislelizumab plus chemotherapy.
• The experimental arm in the DisTinGuish study did not show a significant improvement in PFS compared to the control arm, indicating that the addition of sirexatamab did not provide a clear benefit in this setting.

Stakeholder Impact

• Shareholders may react positively to the promising results in colorectal cancer and the strategic focus on a larger market opportunity.
• Employees may be impacted by the shift in focus from gastric cancer to colorectal cancer.
• Patients with colorectal cancer may benefit from the potential development of a new treatment option.
• Potential partners may be interested in collaborating with Leap on the development of sirexatamab in gastric cancer.

Next Steps

• Leap will begin preparations for a Phase 3 registrational study in second-line colorectal cancer.
• Leap will conduct global commercial and regulatory strategic analysis to select the optimal patient population for the Phase 3 trial.
• Leap will explore strategic partnership opportunities to advance sirexatamab plus anti-PD-1 antibodies in gastric cancer and other indications.

Key Dates

Keywords

sirexatamab, DKN-01, colorectal cancer, gastric cancer, objective response rate, clinical trial, biomarker, DKK1, Phase 3, bevacizumab, tislelizumab, chemotherapy