Gedatolisib + Darolutamide for Prostate Cancer

Recruiting at 13 trial locations

Overseen By Genelle Brower, RN

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Celcuity Inc

Must be taking: LHRH analogs

Must not be taking: PI3K inhibitors, AKT inhibitors

Disqualifiers: Other malignancies, Uncontrolled diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, gedatolisib (an experimental treatment) and darolutamide, to evaluate their safety and effectiveness in treating metastatic castration-resistant prostate cancer (mCRPC). This type of prostate cancer continues to grow despite treatments that lower testosterone. The study includes different groups to determine the best dose and understand how the drugs interact. Men with mCRPC who experience disease progression despite other treatments and can manage daily activities are potential candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any androgen receptor inhibitors at least 4 weeks before starting the study drug. You also need to be at least 2 weeks beyond treatment with targeted therapy or major surgery, and 3 weeks beyond any other systemic anticancer therapy or radiation therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of gedatolisib and darolutamide is under evaluation for safety and effectiveness in treating advanced prostate cancer resistant to hormone therapy. An earlier study with gedatolisib at doses of 120 mg and 180 mg found that no patients discontinued treatment due to side effects, suggesting the combination is generally well-tolerated. Furthermore, no serious side effects required stopping the treatment. While these results are promising, it's important to note that the treatment is still under investigation, and a complete understanding of its safety is still being developed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of gedatolisib and darolutamide for prostate cancer because this duo offers a novel approach compared to current treatments. Gedatolisib is a dual inhibitor, targeting both PI3K and mTOR pathways, which are crucial in cancer cell growth and survival, potentially providing a more comprehensive attack on cancer cells. Darolutamide, on the other hand, is already known for its effectiveness in inhibiting androgen receptors, which are often involved in prostate cancer progression. Together, these drugs might offer a more potent treatment by attacking the cancer through multiple pathways, which could lead to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that combining the drugs gedatolisib and darolutamide may help treat advanced prostate cancer that no longer responds to hormone therapy. Specifically, 66% of patients did not see their cancer worsen for six months. In this trial, participants in Phase 1 Arm 1 will receive 120 mg of gedatolisib. Previous studies showed this dosage increased the percentage to 74%, with the average time before cancer progressed being 9.5 months. These results suggest that this drug combination might effectively slow cancer growth in these patients. ^{2 3 4 6 7}

Who Is on the Research Team?

Nadene Zack, MS

Principal Investigator

Celcuity Inc

Are You a Good Fit for This Trial?

This trial is for men with metastatic castration-resistant prostate cancer (mCRPC). Specific eligibility details are not provided, but typically participants would need to meet certain health standards and have no conflicting conditions.

Inclusion Criteria

I am fully active and can carry on all my pre-disease activities without restriction.

My cancer progressed despite treatment with a specific prostate cancer medication.

My prostate cancer is mainly adenocarcinoma without significant neuroendocrine features.

Exclusion Criteria

I have had cancer before, but it was either skin cancer treated successfully or another type of cancer that has been gone for over 3 years.

My prostate cancer has a small cell component with at least 10% neuroendocrine cells.

I have been treated with a PI3K, AKT, or mTOR inhibitor before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose finding to evaluate safety and determine the recommended Phase 2 dose of gedatolisib in combination with darolutamide

1 year

Weekly visits for gedatolisib administration

Phase 2 Treatment

Assessment of safety and preliminary efficacy of the recommended Phase 2 dose of gedatolisib in combination with darolutamide

6 months

Weekly visits for gedatolisib administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days post last dose

Long-term Follow-up

Assessment of radiographic progression-free survival and overall survival

24 months post Cycle 1 Day 1

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide
• Gedatolisib

Trial Overview The study is testing the combination of two drugs, Gedatolisib and Darolutamide, in patients with mCRPC. It's an early-stage trial to find out the right doses and see how well these drugs work together.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 2 Interventions

The recommended Phase 2 dose (RP2D) of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)

Group II: Phase 1 Arm 2 Experimental Treatment 2 Interventions

Arm 2 - 180 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)

Group III: Phase 1 Arm 1 Experimental Treatment 2 Interventions

Arm 1 - 120 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)

Darolutamide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Nubeqa for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel

Approved in European Union as Nubeqa for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel

Approved in Canada as Nubeqa for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel

Who Is Running the Clinical Trial?

Celcuity Inc

Lead Sponsor

Trials

9

Recruited

1,600+

Published Research Related to This Trial

In the phase 3 ARAMIS trial, darolutamide significantly improved metastasis-free survival and overall survival in men with non-metastatic castration-resistant prostate cancer compared to placebo, indicating its efficacy when combined with ongoing androgen deprivation therapy.

Darolutamide was generally well tolerated, showing a low risk of central nervous system-related side effects, which is a common concern with other second-generation androgen receptor inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Scott, LJ.[2022]

Darolutamide is an effective treatment for nonmetastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer, with potential for broader use in other stages of prostate cancer due to its favorable pharmacokinetic properties.

One of the key advantages of darolutamide is its low distribution to the brain, which reduces the risk of seizures and central nervous system side effects, making it a safer option compared to other androgen receptor signaling inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics and Pharmacodynamics of the Next Generation Androgen Receptor Inhibitor-Darolutamide. Podgoršek, E., Mehra, N., van Oort, IM., et al.[2023]

In a study involving 249 men with metastatic castrate-resistant prostate cancer, patient preference between darolutamide and enzalutamide was balanced, with no significant preference for either treatment (p = 0.92).

Darolutamide was associated with less fatigue and a moderate improvement in episodic memory compared to enzalutamide, suggesting it may offer a better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. Colomba, E., Jonas, SF., Eymard, JC., et al.[2023]

Darolutamide has shown significant efficacy in improving metastasis-free survival in patients with non-metastatic castration-resistant prostate cancer, as demonstrated in the ARAMIS trial.

The treatment landscape for advanced prostate cancer is evolving, with darolutamide being evaluated in ongoing studies for its potential benefits in combination with docetaxel for metastatic castration-sensitive prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide For Castration-Resistant Prostate Cancer. Bastos, DA., Antonarakis, ES.[2020]

In a phase 3 trial involving 1509 men with nonmetastatic, castration-resistant prostate cancer, darolutamide significantly improved metastasis-free survival, with a median of 40.4 months compared to 18.4 months for placebo (hazard ratio 0.41).

The safety profile of darolutamide was comparable to placebo, with similar rates of adverse events and no increased risk of serious side effects like seizures or cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. Fizazi, K., Shore, N., Tammela, TL., et al.[2022]

Darolutamide, a new androgen receptor antagonist, was found to be well tolerated in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC), with most treatment-emergent adverse events being mild (Grade 1/2).

The pharmacokinetics of darolutamide showed a dose-dependent increase in drug levels, and while only 11% of patients showed a prostate-specific antigen response, the drug did not present any new safety concerns compared to Western populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of darolutamide (ODM-201): a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer. Matsubara, N., Mukai, H., Hosono, A., et al.[2023]

Darolutamide (NUBEQA™) is a new non-steroidal androgen receptor antagonist approved for treating non-metastatic castration-resistant prostate cancer in men, based on positive results from the phase III ARAMIS trial.

The approval of darolutamide marks a significant milestone in prostate cancer treatment, highlighting its efficacy and safety profile as demonstrated in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: First Approval. Markham, A., Duggan, S.[2020]

Darolutamide, an oral androgen receptor inhibitor, significantly improves overall survival in patients with metastatic hormone-sensitive prostate cancer when combined with androgen deprivation therapy and docetaxel, compared to placebo.

The treatment with darolutamide has a manageable safety profile, with adverse events aligning with those typically seen in androgen deprivation therapy and docetaxel, making it a viable option for patients with high-volume disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Metastatic Hormone-Sensitive Prostate Cancer. Lee, A.[2023]

Citations

1. urologytimes.com urologytimes.com/view/gedatolisib-plus-darolutamide-shows-encouraging-activity-in-mcrpc

Gedatolisib plus darolutamide shows encouraging activity ... Key Takeaways · Gedatolisib and darolutamide combination showed a 66% 6-month rPFS in mCRPC patients, indicating promising preliminary efficacy.

2. biospace.com biospace.com/press-releases/celcuity-presents-updated-data-at-the-2025-esmo-congress-from-phase-1-study-evaluating-gedatolisib-plus-darolutamide-in-men-with-metastatic-castration-resistant-prostate-cancer-mcrpc

Celcuity Presents Updated Data at the 2025 ESMO ... For patients treated with 120 mg gedatolisib, the six-month rPFS rate was 74% and median rPFS was 9.5 months. For patients treated with 180 mg ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06190899

Study Details | NCT06190899 | Gedatolisib in Combination ... This is a Phase 1/2, open-label, randomized, dose finding and dose expansion study to evaluate the safety, preliminary efficacy, and pharmacokinetics of ...

4. globenewswire.com globenewswire.com/news-release/2025/10/18/3168947/0/en/Celcuity-Presents-Updated-Data-at-the-2025-ESMO-Congress-from-Phase-1-Study-Evaluating-Gedatolisib-Plus-Darolutamide-in-Men-with-Metastatic-Castration-Resistant-Prostate-Cancer-mCR.html

Celcuity Presents Updated Data at the 2025 ESMO Congress For patients treated with 120 mg gedatolisib, the six-month rPFS rate was 74% and median rPFS was 9.5 months. For patients treated with 180 mg ...

5. cancernetwork.com cancernetwork.com/view/early-efficacy-seen-with-gedatolisib-based-therapies-prostate-breast-cancers

Early Efficacy Seen With Gedatolisib-Based Therapies in ... Gedatolisib-involving combinations demonstrated efficacy in metastatic castration-resistant prostate cancer (mCRPC) and HER2-positive metastatic breast cancer.

6. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-prostate-cancer/164103-esmo-2025-celc-g-201-phase-1-2-study-of-gedatolisib-in-combination-with-darolutamide-in-mcrpc.html

ESMO 2025: CELC-G-201: Phase 1/2 Study of Gedatolisib ... Alice Bernard-Tessier discussing a phase 1/2 study of gedatolisib in combination with darolutamide in metastatic castration-resistant prostate ...

7. onclive.com onclive.com/view/gedatolisib-displays-early-efficacy-in-mcrpc-and-pretreated-her2-breast-cancer

Gedatolisib Displays Early Efficacy in mCRPC and ... Gedatolisib combined with darolutamide in mCRPC showed a 66% 6-month rPFS rate, with no treatment discontinuations due to adverse effects. · In ...