8-K: Celcuity Reports Encouraging Early Phase Clinical Data for Gedatolisib in Prostate and Breast Cancers

Celcuity Inc. announced preliminary positive clinical data from two early phase studies of gedatolisib for metastatic castration-resistant prostate cancer and HER2+ metastatic breast cancer, showing promising efficacy and tolerability.

Summary

• Celcuity Inc. reported preliminary clinical data for gedatolisib from two early phase studies.
• In a Phase 1 trial for metastatic castration-resistant prostate cancer (mCRPC) combining gedatolisib with darolutamide, the six-month radiographic progression-free survival (rPFS) rate was 66%.
• No patients discontinued treatment due to treatment-related adverse events (AEs) in this mCRPC trial.
• No Grade 3 hyperglycemia was reported in the mCRPC trial.
• Grade 2-3 stomatitis occurred in four (10.5%) mCRPC patients (7.9% Grade 2, 2.6% Grade 3).
• In an investigator-sponsored Phase 2 trial for HER2+ metastatic breast cancer (mBC) with gedatolisib plus trastuzumab-pkrb, the objective response rate (ORR) was 43% among all enrolled patients.
• Median progression-free survival (PFS) in the HER2+ mBC trial was 6.0 months (95% CI, 5.0-7.7).
• Median overall survival (OS) in the HER2+ mBC trial was 24.7 months (95% CI; 17.3-NA).
• No patients discontinued gedatolisib due to a treatment-related AE in the HER2+ mBC trial.
• One (2.3%) patient experienced Grade 3 hyperglycemia in the HER2+ mBC trial.
• The company amended the mCRPC clinical trial protocol to explore additional gedatolisib doses in Phase 1/1b to determine the recommended Phase 2 dose (RP2D).

Sentiment

Score: 8

Explanation: The clinical data presented for gedatolisib in both mCRPC and HER2+ mBC trials shows promising efficacy and a favorable safety profile, with results comparing favorably to existing therapies. The lack of treatment discontinuations due to adverse events is a significant positive. While further dose exploration is needed for mCRPC, the overall preliminary results are highly encouraging for a clinical-stage asset.

Positives

• Six-month radiographic progression-free survival (rPFS) rate of 66% in the Phase 1 mCRPC trial, which compares favorably to published data for androgen receptor inhibitors in this setting.
• No patients discontinued gedatolisib due to a treatment-related adverse event in either the mCRPC or HER2+ mBC clinical trials.
• No dose reductions were required with gedatolisib or darolutamide in the mCRPC trial.
• No Grade 3 hyperglycemia was reported in the mCRPC trial, and only one (2.3%) patient experienced Grade 3 hyperglycemia in the HER2+ mBC trial.
• Low incidence of Grade 3 stomatitis (2.6%) in the mCRPC trial, despite prophylactic treatment.
• Objective response rate (ORR) of 43% in the Phase 2 HER2+ mBC trial, which is encouraging for patients who had received at least three prior lines of anti-HER2 treatment.
• Median overall survival (OS) of 24.7 months in the HER2+ mBC trial.
• Gedatolisib was well tolerated in both studies.

Negatives

• Grade 2-3 stomatitis was reported in 10.5% of mCRPC patients (7.9% Grade 2, 2.6% Grade 3), despite prophylactic treatment.
• The preliminary data for mCRPC suggests the optimal gedatolisib dose may not yet have been reached, necessitating further dose exploration.

Risks

• Unforeseen delays in clinical trials.
• Ability to obtain and maintain regulatory approvals to commercialize products.
• Market acceptance of products.
• Development of therapies and tools competitive with products.
• Ability to access capital upon favorable terms or at all.
• Risks set forth in the Risk Factors section in the Annual Report on Form 10-K for the year ended December 31, 2024, filed on March 31, 2025.

Future Outlook

The company plans to explore additional dose options for gedatolisib in the mCRPC trial, with up to six patients in each of three arms in the amended Phase 1, followed by up to 40 patients in Phase 1b cohorts to determine the recommended Phase 2 dose (RP2D). The Phase 2 dose expansion study will enroll up to 18 additional subjects to reach approximately 30 subjects treated with RP2D. Additional preliminary results for the mCRPC Phase 1 trial will be presented at a medical conference later this year. The company is also enrolling patients in Phase 3 trials (VIKTORIA-1 and VIKTORIA-2) for HR+/HER2advanced breast cancer.

Management Comments

• "We are very encouraged by this preliminary efficacy and safety data."
• "The 66% six-month rPFS rate for this novel combination therapy compares favorably to published data for androgen receptor inhibitors in this setting."
• "With no treatment-related discontinuations and less than 3% of patients experiencing Grade 3 stomatitis, we believe it is important to explore additional dose options for gedatolisib."
• The company amended the clinical trial protocol to enable exploration of additional doses in the Phase 1/1b portion of this clinical trial to determine the recommended Phase 2 dose, as preliminary data indicates the optimal gedatolisib dose for mCRPC patients may not yet have been reached.
• "The 43% ORR reported in patients who received at least three prior lines of anti-HER2 treatment for their disease is very encouraging and compares favorably to published data for other available therapies in this group of patients."
• "The regimen was well tolerated, and no patients discontinued gedatolisib due to treatment-related AEs."
• "While additional clinical studies are needed, this data suggests gedatolisib in combination with HER2 targeted therapy may be an effective and well tolerated therapeutic option for patients with HER2+ mBC."

Industry Context

Celcuity is a clinical-stage biotechnology company focused on oncology, specifically developing targeted therapies for solid tumors. Gedatolisib, a multi-target inhibitor of the PI3K/AKT/mTOR pathway, is being evaluated in areas with significant unmet medical needs like metastatic castration-resistant prostate cancer (mCRPC) and HER2+ metastatic breast cancer (mBC). The positive early-phase data, particularly the favorable comparison to existing therapies (androgen receptor inhibitors for mCRPC and other anti-HER2 treatments for mBC), positions gedatolisib as a potentially differentiated therapeutic option in these competitive oncology landscapes. The company's strategy to explore optimal dosing and advance to later-stage trials aligns with typical drug development pathways in the biotech industry.

Comparison to Industry Standards

• The 66% six-month rPFS rate for gedatolisib plus darolutamide in mCRPC compares favorably to published data for androgen receptor inhibitors in this setting.
• The 43% ORR in HER2+ mBC patients who received at least three prior lines of anti-HER2 treatment is very encouraging and compares favorably to published data for other available therapies in this group of patients.

Stakeholder Impact

• Shareholders: Positive clinical data could lead to increased investor confidence and potential share price appreciation, especially given the favorable comparison to existing therapies and the advancement of the drug in the pipeline.
• Patients: The promising efficacy and tolerability data suggest gedatolisib could offer a new, effective, and well-tolerated therapeutic option for patients with metastatic castration-resistant prostate cancer and HER2+ metastatic breast cancer, particularly those who have exhausted other treatment options.
• Medical Community: The data provides new insights into the potential of PI3K/AKT/mTOR pathway inhibition in these cancer types, potentially influencing future treatment paradigms and research directions.

Next Steps

• Present additional preliminary results for the Phase 1 portion of the mCRPC clinical trial at a medical conference later this year.
• Enroll up to six patients in each of three arms with different doses in the amended Phase 1 portion of the mCRPC clinical trial.
• Upon completion of Phase 1, randomly assign up to an additional 40 patients to up to four Phase 1b cohorts to determine the recommended Phase 2 dose (RP2D) for mCRPC.
• Enroll up to 18 additional subjects in the Phase 2 dose expansion study for mCRPC to achieve a total of approximately 30 subjects treated with the RP2D.
• Continue enrolling patients in the Phase 3 clinical trial, VIKTORIA-1, evaluating gedatolisib in combination with fulvestrant with or without palbociclib in patients with HR+/HER2advanced breast cancer.
• Continue recruiting patients for the Phase 3 clinical trial, VIKTORIA-2, evaluating gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR+/HER2advanced breast cancer.

Key Dates

Recommendation

Keywords

Celcuity, CELC, gedatolisib, clinical trial, oncology, metastatic castration resistant prostate cancer, mCRPC, HER2+ metastatic breast cancer, mBC, PI3K/AKT/mTOR pathway, targeted therapy, darolutamide, Nubeqa, trastuzumab-pkrb, rPFS, ORR, adverse events, biotechnology, pharmaceutical, drug development, Phase 1, Phase 2, FDA approval