[Ac-225]-PSMA-62 for Prostate Cancer

(ACCEL Trial)

Recruiting at 9 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company

Must not be taking: PSMA-directed radioligands, Systemic radionuclides

Disqualifiers: Urinary obstruction, Liver metastases, others

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

Compensation: Varies

Number of Visits: Unknown

142 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called [Ac-225]-PSMA-62 for prostate cancer that shows a specific marker called PSMA. The goal is to evaluate the treatment's effectiveness for two groups: those whose cancer has returned after surgery or radiation but have not started hormone therapy, and those with more advanced cancer who have tried other treatments. A suitable candidate for this trial might have prostate cancer with PSMA markers and has experienced disease recurrence or progression despite prior treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received any investigational therapeutic agents within 4 weeks or 5 half-lives of starting the study treatment.

Is there any evidence suggesting that [Ac-225]-PSMA-62 is likely to be safe for humans?

Research shows that [Ac-225]-PSMA-62 holds promise for safety in prostate cancer patients. Previous studies have examined its safety and patient tolerance. For instance, one study identified the highest dose patients could take without serious side effects. Another study found that treatments with [Ac-225]-PSMA, a type of targeted therapy, are generally safe when used alone or with other treatments.

So far, many patients have tolerated [Ac-225]-PSMA-62 well, with no major safety issues reported in these studies. However, since the current trial is in an early stage, researchers continue to closely monitor the treatment to ensure it remains safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about [Ac-225]-PSMA-62 for prostate cancer because it offers a novel approach to targeting cancer cells. Unlike traditional treatments like hormone therapy or chemotherapy, which can affect both healthy and cancerous cells, [Ac-225]-PSMA-62 uses a radioactive isotope, Actinium-225, linked to a molecule that specifically targets the Prostate-Specific Membrane Antigen (PSMA) on cancer cells. This targeted delivery allows for a more precise attack on cancer cells while minimizing damage to surrounding healthy tissue. Additionally, this method is promising for patients with biochemical recurrence and those with metastatic castration-resistant prostate cancer (mCRPC), offering new hope where other treatments have limited success.

What evidence suggests that [Ac-225]-PSMA-62 could be an effective treatment for prostate cancer?

Research has shown that treatments targeting PSMA, a protein on prostate cancer cells, hold promise for prostate cancer. For instance, studies with treatments like [Ac-225]-PSMA-617 have effectively controlled cancer with manageable side effects in patients with advanced prostate cancer. This trial examines [Ac-225]-PSMA-62, a similar treatment, in different patient groups. It attaches a radioactive particle to PSMA, delivering radiation directly to cancer cells, which can shrink tumors and slow the disease. Early research suggests that [Ac-225]-PSMA-62 could be effective, particularly for patients with PSMA-positive prostate cancer. Although this approach remains under study, the results so far are encouraging for those with this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced prostate cancer that's resistant to hormone therapy and has come back after treatment. They must have good organ function, an ECOG performance status of 0-2, a life expectancy of at least 6 months, and agree to use two forms of contraception. People with HIV can join if they're healthy. Participants should be out of other treatment options.

Inclusion Criteria

Patients and their female partner(s) of childbearing potential must agree to use two acceptable forms of contraception, one of which must be a barrier method during the study and for 21 weeks after last study drug administration

The patient has read, understood, and signed the written informed consent form(s)

Criteria specific for patients with mCRPC:

Exclusion Criteria

My cancer has spread to my liver.

My prostate cancer is of the neuroendocrine or small cell type.

Inability to lie flat during or tolerate PET/CT or MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ia Treatment

Evaluation of safety and tolerability to determine the maximum tolerated dose (MTD) of [Ac-225]-PSMA-62

4 weeks

Multiple visits for dose administration and monitoring

Phase Ib Treatment

Randomized dose optimization to determine the recommended phase II doses (RP2D)

16-24 weeks

Regular visits for treatment and monitoring of adverse events

Phase II Treatment

Evaluation of efficacy of [Ac-225]-PSMA-62 in patients with mCRPC

16-24 weeks

Regular visits for treatment and efficacy assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Periodic visits for long-term monitoring

What Are the Treatments Tested in This Trial?

Interventions

• [Ac-225]-PSMA-62

Trial Overview [Ac-225]-PSMA-62 is being tested in this phase I/II study on patients whose prostate cancer cells have PSMA. The trial aims to see how safe it is and how well it works across multiple centers where everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: mCRPC Experimental Treatment 1 Intervention

Patients with PSMA-positive mCRPC who have prior treatment with at least one APRI and received taxane chemotherapy (or ineligible/refused); and received a maximum of 3 prior systemic therapy regimens in the mCRPC setting.

Group II: OmHSPC Experimental Treatment 1 Intervention

Patients with prostate cancer and biochemical recurrence after definitive surgery or radiation therapy, with 1-5 PSMA-positive lesions, who have not yet initiated lifelong hormone therapy.

Who Is Running the Clinical Trial?

POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company

Lead Sponsor

Trials

5

Recruited

670+

POINT Biopharma

Lead Sponsor

Trials

6

Recruited

720+

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

The LUNAR trial is investigating the efficacy of 177 Lu-PNT2002, a radiolabelled small molecule targeting prostate-specific membrane antigen (PSMA), in combination with stereotactic body radiotherapy (SBRT) for men with oligorecurrent metastatic hormone-sensitive prostate cancer, with 100 patients expected to be enrolled.

This Phase 2 trial aims to determine if adding 177 Lu-PNT2002 to SBRT can improve progression-free survival and other outcomes compared to SBRT alone, potentially offering a new treatment strategy for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LUNAR: a randomized Phase 2 study of 177 Lutetium-PSMA Neoadjuvant to Ablative Radiotherapy for Oligorecurrent Prostate Cancer (clinical trial protocol). Ma, TM., Czernin, J., Felix, C., et al.[2023]

The newly designed PSMA-NAT-DA1 (PNT-DA1) shows significantly improved affinity for prostate-specific membrane antigen (PSMA) and higher tumor accumulation compared to the previous PSMA-DA1, indicating enhanced effectiveness for targeting metastatic castration-resistant prostate cancer.

Administration of [225Ac]Ac-PNT-DA1 resulted in tumor shrinkage with minimal toxicity, outperforming existing PSMA-targeting therapies, suggesting that PNT-DA1 could be a superior option for radiotheranostic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Novel 111In/225Ac-Labeled Agent Targeting PSMA for Highly Efficient Cancer Radiotheranostics. Tsuchihashi, S., Nakashima, K., Tarumizu, Y., et al.[2023]

Radionuclide therapy (RNT) using beta and alpha particles, specifically lutetium-177 (177Lu) and actinium-225 (225Ac) labeled PSMA, shows promise as a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), targeting prostate-specific membrane antigen (PSMA) which is highly expressed in cancer cells.

Clinical studies indicate that these therapies may provide a survival benefit for mCRPC patients, although the field is still developing and further research is needed to fully establish their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in 177Lu-PSMA and 225Ac-PSMA Radionuclide Therapy for Metastatic Castration-Resistant Prostate Cancer. Ling, SW., de Blois, E., Hooijman, E., et al.[2022]

In a study of 56 patients with metastatic castration-resistant prostate cancer (mCRPC) who had exhausted standard treatments, [225Ac]Ac-PSMA-617 targeted alpha therapy showed promising efficacy, with 91% of patients experiencing a decline in prostate-specific antigen (PSA) levels, and a median overall survival of 15 months.

The treatment was well-tolerated, with most adverse events being mild to moderate, such as transient fatigue in 70% of patients and xerostomia in about one-third, indicating that [225Ac]Ac-PSMA-617 could be a viable option for patients with advanced mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival outcomes of salvage [225Ac]Ac-PSMA-617 targeted alpha therapy in patients with PSMA-expressing end-stage metastatic castration-resistant prostate cancer: a real-world study. Ballal, S., Yadav, MP., Satapathy, S., et al.[2023]

The FDA has approved 177Lu-PSMA-617 for treating advanced metastatic castrate-resistant prostate cancer (mCRPC), marking a significant advancement in PSMA-targeted therapies.

Various PSMA-targeted radiopharmaceuticals, including both beta and alpha emitters, are in development, with promising results for alpha therapies like 225Ac-PSMA-617, although there are concerns about potential toxicity to salivary and renal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts. Sartor, O., Baghian, A.[2022]

In a study of 11 heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with Actinium-225 (225Ac) labeled PSMA-617 led to a significant improvement in quality of life, as measured by the NCCN-FACT-FPSI-17 questionnaire, particularly in physical and emotional symptoms.

The therapy resulted in a notable biochemical response, with 46% of patients experiencing a significant decline in Prostate Specific Antigen (PSA) levels, while the treatment was associated with manageable side effects, including some Grade 3 toxicities in a small number of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality-of-Life Outcomes with Actinium-225-Prostate-Specific Membrane Antigen-617 Therapy in Patients with Heavily Pretreated Metastatic Castration-Resistant Prostate Cancer. Satapathy, S., Mittal, BR., Sood, A., et al.[2022]

In a study of 13 patients with advanced metastatic castration-resistant prostate cancer (mCRPC), treatment with 225Ac-PSMA targeted alpha-radiation therapy resulted in a median overall survival of 8.5 months, with even better outcomes (12.6 months) for patients who had not previously received PSMA therapy.

Patients experienced significant improvements in quality of life and pain relief, although xerostomia (dry mouth) was a persistent side effect; high baseline PSMA expression and DNA damage repair alterations were identified as potential biomarkers for predicting better survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes and molecular profiling of advanced metastatic castration-resistant prostate cancer patients treated with 225Ac-PSMA-617 targeted alpha-radiation therapy. van der Doelen, MJ., Mehra, N., van Oort, IM., et al.[2022]

In a first-in-human trial, two patients with advanced prostate cancer showed a complete response to treatment with 225Ac-PSMA-617, indicating its potential efficacy as a targeted therapy.

The treatment resulted in a significant decline in prostate-specific antigen levels without relevant hematologic toxicity, suggesting a favorable safety profile, with xerostomia being the only notable side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer. Kratochwil, C., Bruchertseifer, F., Giesel, FL., et al.[2022]

The new 211At-labeled radiotracer, 211At-3-Lu, effectively targets prostate-specific membrane antigen (PSMA) in prostate cancer cells, showing significant uptake in PSMA+ tumors with minimal uptake in non-target cells, indicating its potential for targeted therapy.

In a long-term toxicity study, 211At-3-Lu demonstrated low off-target toxicity and favorable safety profiles, including stable hematopoietic function and positive histopathological outcomes, suggesting it could be a safe and effective treatment option for patients with prostate cancer resistant to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Improved 211At-Labeled Agent for PSMA-Targeted α-Therapy. Mease, RC., Kang, CM., Kumar, V., et al.[2022]

PSMA-targeted thorium-227 conjugate (PSMA-TTC) effectively targets and induces DNA damage in prostate cancer cells, leading to cell death, particularly in cells with high PSMA expression.

In preclinical models, PSMA-TTC demonstrated strong antitumor efficacy, significantly reducing tumor growth and abnormal bone growth associated with metastatic prostate cancer, supporting its potential for clinical evaluation in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Efficacy of a PSMA-Targeted Thorium-227 Conjugate (PSMA-TTC), a Targeted Alpha Therapy for Prostate Cancer. Hammer, S., Hagemann, UB., Zitzmann-Kolbe, S., et al.[2021]

177Lu-PSMA is an effective treatment for advanced prostate cancer, lowering PSA levels and improving quality of life, but about one-third of patients may not respond well to this therapy, highlighting the need for better personalization of treatment.

225Ac-PSMA shows promise for tumors resistant to standard treatments, offering a better response than 177Lu-PSMA, but it poses risks of significant damage to healthy tissues, necessitating careful dosimetry and potential use of nano-carriers for safer delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of 177Lutetium-PSMA and 225Actinium-PSMA as Emerging Theranostic Agents in Prostate Cancer. Alam, MR., Singh, SB., Thapaliya, S., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS282

ACCEL: [Ac-225]-PSMA-62 phase Ia/Ib/II clinical trial to ... A multi-center, open-label, multiple-arm, Phase Ia/Ib/II study evaluating the safety, tolerability, and efficacy of [Ac-225]-PSMA-62 in patients with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06229366

Study Details | NCT06229366 | [Ac-225]-PSMA-62 Trial in ... The primary aim of the phase Ia study is to evaluate the safety and tolerability of [Ac-225]-PSMA-62 to determine the maximum tolerated dose (MTD).

3. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158157-asco-gu-2025-accel-ac-225-psma-62-phase-ia-ib-ii-clinical-trial-to-characterize-efficacy-safety-tolerability-and-dosimetry-in-oligometastatic-hormone-sensitive-and-metastatic-castration-resistant-prostate-cancer.html

ASCO GU 2025: ACCEL: [Ac-225]-PSMA-62 Phase Ia/Ib/II ... A phase Ia Ia/Ib/II clinical trial to characterize the efficacy, safety, tolerability, and dosimetry of [Ac-225]-PSMA-62 in oligometastatic hormone-sensitive ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39552586

[225Ac]Ac-PSMA for the treatment of metastatic castration ... Overall, the main results of our study showed that [ 225 Ac]Ac-PSMA-617 had a significant therapeutic effect on mCRPC with an acceptable toxicity level.

5. trialx.com trialx.com/clinical-trials/listings/289317/ac-225-psma-62-trial-in-biochemically-recurrent-and-metastatic-castration-resistant-prostate-cancer/

[Ac-225]-PSMA-62 Trial in Biochemically Recurrent and ... The primary aim of the phase I study is to evaluate the safety and tolerability of [Ac-225]-PSMA-62 to determine recommended phase II doses for ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39941774/

Long-Term Safety and Survival Outcomes of [225Ac]Ac- ... This study demonstrates that [ 225 Ac]Ac-PSMA PRLT, both as monotherapy and combined with [ 177 Lu]Lu-PSMA as TANDEM PRLT, is generally safe.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11816130/

Long-Term Safety and Survival Outcomes of [225Ac]Ac- ... This study investigates the safety of Radioligand Therapy with [225Ac]Ac-PSMA in patients with metastatic castration-resistant prostate cancer ...