8-K: Relay Therapeutics' Zovegalisib Phase 1/2 Data Positive

Relay Therapeutics announced positive Phase 1/2 ReDiscover trial data for zovegalisib in PI3K-mutated metastatic breast cancer, supporting its Phase 3 advancement.

Summary

• Relay Therapeutics announced data from the Phase 1/2 ReDiscover trial of zovegalisib (RLY-2608) in combination with fulvestrant.
• The data pertains to the recommended Phase 3 dose of 400mg twice daily (BID) taken with food (fed) in patients with PI3K-mutated, HR+/HER2metastatic breast cancer.
• The efficacy population consisted of 57 patients who did not have a PTEN or AKT co-mutation, all of whom had previously received a CDK4/6 inhibitor and at least one prior endocrine therapy.
• Median follow-up for the efficacy-evaluable patients was 12.0 months.
• Median progression-free survival (PFS) was 11.1 months (95% confidence interval: 7.3-13.0 months).
• PFS was 11.2 months in patients with kinase mutations (n=33) and 11.0 months in patients with non-kinase mutations (n=24).
• Among 35 patients with measurable disease, the confirmed objective response rate (ORR) was 43% (15/35).
• In second-line only patients with measurable disease, the ORR was 52% (11/21).
• The 400mg BID fed dose was generally well tolerated in 60 treated patients, with a safety profile consistent with previously disclosed 600mg BID fasted data.
• The overall tolerability profile primarily consisted of low-grade, manageable, and reversible treatment-related adverse events (TRAEs).
• The majority of hyperglycemia events were Grade 1, with no Grade 4-5 hyperglycemia observed.
• Only four patients discontinued due to TRAEs.
• Zovegalisib in combination with fulvestrant has received FDA Breakthrough Therapy designation for the Phase 3 ReDiscover-2 trial population.

Sentiment

Score: 8

Explanation: StockSavvy.ai views this as a highly positive announcement, driven by strong efficacy data (PFS, ORR) and a differentiated, favorable tolerability profile for zovegalisib, further bolstered by FDA Breakthrough Therapy designation.

Positives

• Median progression-free survival (PFS) of 11.1 months in heavily pre-treated patients with PI3K-mutated, HR+/HER2metastatic breast cancer.
• Consistent efficacy observed across patients with kinase mutations (11.2 months PFS) and non-kinase mutations (11.0 months PFS).
• Objective response rate (ORR) of 43% in patients with measurable disease, increasing to 52% in second-line only patients.
• Generally well-tolerated safety profile, consistent with previous data, featuring primarily low-grade, manageable, and reversible treatment-related adverse events.
• Low incidence of severe hyperglycemia, with no Grade 4-5 events observed and most Grade 2/3 cases occurring in pre-diabetic patients.
• Only four patients discontinued due to TRAEs, indicating good overall tolerability.
• FDA Breakthrough Therapy designation received for the Phase 3 ReDiscover-2 trial population, highlighting the drug's potential to address an unmet medical need.
• The 400mg BID fed regimen achieved exposures comparable to the previously evaluated 600mg BID fasted dose while maintaining robust efficacy.

Risks

• The impact of global economic uncertainty, geopolitical instability, conflicts, or public health epidemics on operations, clinical trials, strategy, and profitability.
• Significant political, trade, or regulatory developments, such as tariffs, beyond the company's control.
• The delay or pause of any current or planned clinical trials or the development of drug candidates.
• The risk that preliminary or interim results of preclinical or clinical trials may not be predictive of future or final results in connection with future clinical trials.
• Interim and early clinical data may change as more patient data become available and are subject to audit and verification procedures.
• The ability to successfully demonstrate the safety and efficacy of drug candidates.
• The timing and outcome of planned interactions with regulatory authorities and any related approvals.
• Obtaining, maintaining, and protecting intellectual property.

Future Outlook

The company plans to advance zovegalisib into the ongoing Phase 3 ReDiscover-2 trial, which initiated in mid-2025 and is enrolling globally. Management expresses confidence in selectively targeting PI3K mutations as a potentially differentiated approach for CDK4/6-experienced patients. Zovegalisib has the potential, if approved, to address a significant patient population of approximately 140,000 patients with HR+/HER2breast cancer with a PI3K mutation and an estimated 170,000 patients with vascular anomalies driven by a PI3K mutation per year in the United States.

Management Comments

• "The 400mg BID fed regimen maintains robust efficacy with a safety profile consistent with mutant-selective PI3K inhibition." Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics.
• "These results further support our decision to advance this regimen into the ongoing Phase 3 ReDiscover-2 trial and reinforce our confidence in selectively targeting PI3K mutations as a potentially differentiated approach for CDK4/6-experienced patients." Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics.

Industry Context

StockSavvy.ai notes that the positive Phase 1/2 data for zovegalisib, particularly its efficacy and favorable tolerability profile in heavily pre-treated PI3K-mutated HR+/HER2metastatic breast cancer patients, positions Relay Therapeutics favorably in the competitive oncology landscape. The FDA Breakthrough Therapy designation underscores the potential for zovegalisib to address an unmet medical need, especially given the challenges associated with previous PI3K inhibitors' toxicity and lack of mutant selectivity. This development could strengthen Relay's position against other companies developing targeted therapies for breast cancer.

Comparison to Industry Standards

• The median PFS of 11.1 months for zovegalisib in heavily pre-treated patients with PI3K-mutated, HR+/HER2metastatic breast cancer compares favorably to some existing therapies or historical controls in this challenging patient population. For instance, alpelisib (Piqray), another PI3K inhibitor approved for PIK3CA-mutated HR+/HER2advanced breast cancer, showed a median PFS of 11.0 months in the PIK3CA-mutated cohort of the SOLAR-1 trial when combined with fulvestrant, compared to 5.7 months for fulvestrant alone. Zovegalisib's 11.1 months PFS is in a similar range, but importantly, it is presented with a differentiated tolerability profile and mutant-selective mechanism.
• The objective response rate (ORR) of 43% (52% in second-line only patients) is also competitive. In the SOLAR-1 trial, alpelisib + fulvestrant achieved an ORR of 36% in the PIK3CA-mutated cohort.
• The claim of a "favorable and differentiated tolerability profile" with primarily low-grade, manageable, and reversible TRAEs, and no Grade 4-5 hyperglycemia, suggests an improvement over previous PI3K inhibitors which have been associated with significant toxicities, particularly hyperglycemia and rash, often leading to dose reductions or discontinuations.

Stakeholder Impact

• Shareholders: Positive impact due to strong clinical data, potential for future market approval, and FDA Breakthrough Therapy designation, which could increase company valuation and stock price.
• Patients: Potential for a new, effective, and better-tolerated treatment option for PI3K-mutated, HR+/HER2metastatic breast cancer, and PI3K-driven vascular anomalies.
• Healthcare Providers: Provides a promising new therapeutic agent to consider for patients with specific breast cancer mutations.

Next Steps

• Continue the ongoing Phase 3 ReDiscover-2 trial (NCT06982521) globally.
• Further evaluate zovegalisib in multiple metastatic breast cancer studies.
• Continue the first-in-human study designed to treat patients with PIK3CA (PI3K) mutation driven vascular anomalies.

Key Dates

Recommendation

The strong Phase 1/2 clinical trial results for zovegalisib, demonstrating significant progression-free survival and objective response rates with a favorable and differentiated tolerability profile, are highly encouraging. The FDA Breakthrough Therapy designation further de-risks the development pathway and highlights the drug's potential to address a significant unmet medical need. These factors, combined with the advancement to a global Phase 3 trial, suggest a strong growth trajectory and potential for market success, making it a compelling investment opportunity.

Keywords

Relay Therapeutics, RLAY, Zovegalisib, RLY-2608, PI3K-mutated breast cancer, metastatic breast cancer, HR+/HER2-, ReDiscover trial, Phase 1/2, Phase 3, fulvestrant, oncology, precision medicine, Breakthrough Therapy designation, PFS, ORR, clinical trial data