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

Relay Therapeutics reported positive interim clinical data for RLY-2608, showing a 9.2-month median progression-free survival in heavily pre-treated patients with PI3K-mutated, HR+/HER2metastatic breast cancer.

Summary

• Relay Therapeutics announced interim clinical data for RLY-2608, a PI3K inhibitor, in combination with fulvestrant for patients with PI3K-mutated, HR+, HER2metastatic breast cancer.
• The data is from the ReDiscover trial, with a data cut-off of August 12, 2024.
• 118 patients were enrolled in the RLY-2608 and fulvestrant combination arm, with 64 patients receiving the recommended Phase 2 dose (RP2D) of 600mg twice daily.
• Among the 52 patients at the RP2D without PTEN or AKT co-mutations, the median progression-free survival (PFS) was 9.2 months across all mutations and 10.3 months for those with kinase mutations.
• The clinical benefit rate (CBR) was 57% across all patients, and the objective response rate (ORR) was 33% in patients with measurable disease.
• In patients with kinase mutations and measurable disease, the ORR was 53%.
• RLY-2608 in combination with fulvestrant was generally well-tolerated, with mostly low-grade treatment-related adverse events (TRAEs).
• Only two patients discontinued treatment due to TRAEs at the RP2D.
• The company plans to initiate a 2L pivotal study in 2025 and is progressing two front-line triplet regimens.
• The company also met with the FDA regarding lirafugratinib, with the FDA suggesting an NDA filing in cholangiocarcinoma first, followed by a tumor agnostic supplemental NDA.
• Relay Therapeutics plans to seek a global commercialization partner for lirafugratinib.

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 also has a solid cash position and clear plans for future development. The sentiment is very positive, but not a perfect 10 due to the inherent risks in drug development and the need for regulatory approvals.

Positives

• RLY-2608 showed clinically meaningful progression-free survival in a heavily pre-treated patient population.
• The tolerability profile of RLY-2608 was favorable, with a low rate of treatment-related adverse events.
• The company is advancing multiple clinical programs, including triplet combinations and monotherapy studies.
• The company has a strong cash position, expected to fund operations into the second half of 2026.
• The company is planning a pivotal study for RLY-2608 in 2025.

Negatives

• The document notes that the data is interim and may change as more patient data becomes available.
• The company is seeking a commercialization partner for lirafugratinib, which may indicate a shift in focus or resource allocation.
• The company is reliant on regulatory approvals for the progression of its clinical programs.

Risks

• The company's clinical trials may be delayed or paused due to various factors.
• Preliminary results may not be predictive of future or final results.
• The company may not be able to successfully demonstrate the safety and efficacy of its drug candidates.
• The company's interactions with regulatory authorities may not result in approvals.
• The company may face challenges in 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 2L pivotal study of RLY-2608 in 2025, progress two front-line triplet regimens, and initiate monotherapy solid tumor and vascular malformation studies. They also plan to seek a global commercialization partner for lirafugratinib and advance other programs, including Fabry disease and NRAS.

Management Comments

• Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics, stated that the interim data suggests RLY-2608 has the potential to offer a level of benefit to patients that has not previously been possible with existing non-selective medicines, while also having significantly less toxicity.
• Management is very encouraged to see that RLY-2608 + fulvestrant led to clinically meaningful progression free survival in heavily pre-treated patients with PI3K-mutated, HR+, HER2metastatic breast cancer.
• Management will move quickly to share these data with regulators and align on the design of a pivotal study, which they anticipate starting in 2025.

Industry Context

This announcement is significant in the context of the ongoing development of targeted therapies for breast cancer, particularly for patients with PI3K mutations. The positive data for RLY-2608 suggests a potential new treatment option with improved efficacy and tolerability compared to existing non-selective PI3K inhibitors. The company's focus on mutant-selective inhibition is a key differentiator in the competitive landscape.

Comparison to Industry Standards

• The reported median PFS of 9.2 months for RLY-2608 in combination with fulvestrant compares favorably to the 5.5 months reported for capivasertib plus fulvestrant in the CAPItello-291 trial, particularly given the heavier pre-treatment of the patients in the Relay Therapeutics trial.
• The 33% ORR across all patients and 53% ORR in patients with kinase mutations is also competitive with other PI3K inhibitors in this setting.
• The tolerability profile of RLY-2608 appears to be better than that of other PI3K inhibitors, with a lower rate of Grade 3+ adverse events and fewer discontinuations due to TRAEs.
• The company is positioning RLY-2608 as a potential competitor to capivasertib in the 2L setting for PIK3CA-mutated breast cancer.
• The company is also exploring triplet combinations with ribociclib and atirmociclib, which could further enhance the efficacy of RLY-2608.

Stakeholder Impact

• Shareholders: The positive clinical data and strong cash position are likely to be viewed favorably by shareholders.
• Patients: The potential for a new, more effective and better-tolerated treatment option for breast cancer is a positive development for patients.
• Employees: The advancement of clinical programs and the company's financial stability are positive for employees.
• Partners: The company's plans to seek a commercialization partner for lirafugratinib may impact potential partners.

Next Steps

• Initiate a 2L pivotal study of RLY-2608 + fulvestrant in 2025.
• Report initial safety data for RLY-2608 + ribociclib + fulvestrant in the fourth quarter of 2024.
• Initiate RLY-2608 + ribociclib + fulvestrant triplet dose expansion cohort(s) in the first half of 2025.
• Initiate RLY-2608 + atirmociclib (CDK4) + fulvestrant triplet by the end of 2024.
• Initiate RLY-2608 monotherapy solid tumor dose expansion cohort(s) by the end of 2024.
• Initiate vascular malformations study in the first quarter of 2025.
• Seek a global commercialization partner for lirafugratinib.

Key Dates

Keywords

RLY-2608, PI3K inhibitor, breast cancer, clinical trial, progression-free survival, lirafugratinib, oncology, metastatic, drug development, precision medicine