8-K: Relay Therapeutics Announces Positive Interim Data for RLY-2608 in Breast Cancer

Relay Therapeutics reports promising interim clinical data for RLY-2608, showing a median progression-free survival of 11.4 months in second-line breast cancer patients.

Summary

• Relay Therapeutics announced updated interim clinical data for RLY-2608, a novel PI3K inhibitor, from the ReDiscover study.
• The data, as of November 4, 2024, includes 118 patients with PI3K-mutated, HR+, HER2locally advanced or metastatic breast cancer.
• 64 patients received the recommended Phase 2 dose (RP2D) of 600mg twice daily of RLY-2608 in combination with fulvestrant.
• Among 52 patients at the RP2D without PTEN or AKT co-mutations, the median progression-free survival (PFS) was 9.2 months overall and 11.4 months for second-line patients.
• The clinical benefit rate (CBR) was 67% across all patients, and the confirmed objective response rate (ORR) was 39% in patients with measurable disease.
• For the 15 patients with measurable disease and a kinase mutation, the ORR was 67%.
• RLY-2608 in combination with fulvestrant was generally well-tolerated, with mostly low-grade treatment-related adverse events (TRAEs).
• The company is progressing two front-line triplet regimens with RLY-2608, one with ribociclib and another with atirmociclib.
• Relay Therapeutics plans to initiate a second-line pivotal study of RLY-2608 plus fulvestrant in 2025.

Sentiment

Score: 8

Explanation: The document presents very positive interim clinical data for RLY-2608, with strong efficacy and a favorable tolerability profile. The company is also well-funded and has clear plans for future development. The sentiment is very positive from an investment perspective.

Positives

• The median PFS of 11.4 months in second-line patients is a significant improvement over existing standards of care.
• The 67% clinical benefit rate indicates a substantial proportion of patients are experiencing disease control.
• The 39% objective response rate, and 67% in kinase mutation patients, suggests a strong anti-tumor effect.
• The tolerability profile is favorable, with a low rate of serious adverse events and treatment discontinuations.
• The high median dose intensity of 94% indicates that patients are able to stay on the treatment regimen.
• The company is progressing two front-line triplet regimens, expanding the potential use of RLY-2608.
• The company has a strong cash position of approximately $840 million as of the end of the third quarter of 2024.

Negatives

• Some patients experienced treatment-related adverse events, although most were low-grade and manageable.
• 31% of patients experienced a Grade 3 TRAE, although no Grade 4-5 TRAEs were reported.
• The study is still in the interim phase, and final results may differ.

Risks

• The clinical trial results are preliminary and may not be predictive of future or final results.
• The company's ability to successfully demonstrate the safety and efficacy of RLY-2608 is not guaranteed.
• There are risks associated with the timing and outcome of interactions with regulatory authorities.
• The company faces risks related to obtaining, maintaining, and protecting its intellectual property.
• Global economic uncertainty, geopolitical instability, and public health issues could impact the company's operations and clinical trials.

Future Outlook

The company plans to initiate a second-line pivotal study of RLY-2608 plus fulvestrant in 2025 and disclose complete Phase 1/2 data in 2025. They also plan to initiate a vascular malformations study in the first quarter of 2025. The company expects its cash balance to fund operations into the second half of 2027.

Management Comments

• Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics, stated that the updated data builds on previously reported results and shows a level of benefit not previously seen with non-selective PI3K inhibitors.
• Management is particularly encouraged to see even greater benefit observed in the patients in which they are working to start a pivotal study next year.

Industry Context

This announcement is significant as it presents a potential new treatment option for patients with PI3K-mutated breast cancer, a population with limited effective therapies. The results suggest that RLY-2608 may offer improved efficacy and tolerability compared to existing non-selective PI3K inhibitors. The company is also exploring triplet combinations, which could further enhance the drug's potential.

Comparison to Industry Standards

• The reported median PFS of 11.4 months in second-line patients compares favorably to existing treatments like capivasertib plus fulvestrant, which showed a 5.5 month mPFS in a similar patient population.
• Alpelisib plus fulvestrant has shown a mPFS of 5.6-8 months, and other treatments like CDK4/6 inhibitors plus fulvestrant have shown mPFS of 16-20 months in different patient populations.
• The 67% clinical benefit rate for RLY-2608 is higher than the 56% reported for capivasertib in a similar population.
• The tolerability profile of RLY-2608 appears better than other PI3K inhibitors, with a lower rate of Grade 3+ hyperglycemia and other adverse events.
• The company is also exploring triplet combinations, which could further enhance the drug's potential, and is in line with current industry trends.

Stakeholder Impact

• Shareholders: The positive clinical data and future plans are likely to be viewed favorably by investors.
• Patients: The results suggest a potential new treatment option for patients with PI3K-mutated breast cancer.
• Employees: The company's progress and financial stability are positive for employees.
• Partners: The collaboration with Pfizer on the atirmociclib triplet regimen is a positive development.

Next Steps

• Initiate a second-line pivotal study of RLY-2608 plus fulvestrant in 2025.
• Disclose complete Phase 1/2 data in 2025.
• Initiate a vascular malformations study in the first quarter of 2025.
• Continue dose escalation for the RLY-2608, fulvestrant and ribociclib triplet regimen.
• Continue enrollment in the RLY-2608, fulvestrant and atirmociclib arm of the ReDiscover study.

Key Dates

Keywords

RLY-2608, PI3K inhibitor, breast cancer, clinical trial, progression-free survival, objective response rate, metastatic breast cancer, targeted therapy, fulvestrant, kinase mutation, ReDiscover study, adverse events