Tarlatamab for Prostate Cancer

(DeLLpro-300 Trial)

Recruiting at 22 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Amgen

Must be taking: LHRH analogue

Must not be taking: Immunosuppressive therapy

Disqualifiers: Hematological malignancies, Brain metastases, Autoimmune disease, HIV, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

41 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called Tarlatamab to see if it is safe for people to use. The goal is to find out the best dose to give. The study will help determine if Tarlatamab can be a good treatment option for patients who need new therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must continue taking luteinizing hormone-releasing hormone (LHRH) analogue therapy if you have not had a bilateral orchiectomy. You can also continue hormone deprivation therapy and stable bisphosphonate or denosumab treatments.

Is Tarlatamab safe for humans?

Tarlatamab (also known as AMG 757) has been tested in clinical trials for small-cell neuroendocrine prostate cancer, showing significant antitumor activity. While the study highlights its effectiveness, it does not provide specific safety data, so it's important to discuss potential risks with your healthcare provider. ^{1 2 3 4 5}

What makes the drug Tarlatamab unique for prostate cancer treatment?

Tarlatamab is unique because it is a bispecific T-cell engager (BiTE) immunotherapy that targets DLL3, a protein found in aggressive forms of prostate cancer, and redirects T cells to kill cancer cells, offering a novel approach compared to traditional treatments. ^{1 2 3 6 7}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for men over 18 with advanced prostate cancer showing neuroendocrine features, who've had at least one prior systemic treatment. They must have measurable disease, be in fairly good health (ECOG ≤2), and have proper organ function. Men on hormone therapy must continue it during the study. Those with untreated brain metastases or certain other conditions are excluded.

Inclusion Criteria

Participant has provided informed consent prior to initiation of any study specific activities/procedures.

I have had treatment for brain metastases and meet specific criteria.

I have received at least one round of systemic treatment.

Exclusion Criteria

I haven't had cancer treatment in the last 28 days, but I may be on hormone therapy for prostate cancer or stable bone medication.

I have brain metastases or leptomeningeal disease that hasn't been treated or is causing symptoms.

My cancer was treated with the goal of cure, and I've been cancer-free for over 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

Participants receive varying doses to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)

Duration not specified

Dose Expansion

Participants receive the RP2D/MTD identified in the dose exploration phase

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Tarlatamab

Trial Overview The trial is testing Tarlatamab to find out how safe it is and what dose can be given without causing severe side effects. It aims to establish the maximum tolerated dose or a recommended dose for future Phase 2 trials.

Participant Groups

Group I: Part 2: Dose Expansion Experimental Treatment 1 Intervention

Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study.

Group II: Part 1: Dose Exploration Experimental Treatment 1 Intervention

The maximum tolerated dose (MTD) will be estimated using isotonic regression (Ji et al, 2010). The recommended phase 2 dose (RP2D) may be identified based on emerging safety data prior to reaching an MTD.

Tarlatamab is already approved in United States for the following indications:

Approved in United States as Imdelltra for:

• Extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Findings from Research

Neoadjuvant androgen deprivation therapy with abiraterone acetate plus prednisone and leuprolide (Neo-AAPL) did not increase PD-L1 expression in prostate cancer, showing a trend toward decreased PD-L1 positivity compared to untreated controls (7% vs. 21%).

Neo-AAPL treatment also resulted in significantly fewer tumor-infiltrating CD8+ cells, suggesting that combining this treatment with PD-L1/PD-1 blockade may not be effective in enhancing immune response in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of PD-L1 in Hormone-naïve and Treated Prostate Cancer Patients Receiving Neoadjuvant Abiraterone Acetate plus Prednisone and Leuprolide. Calagua, C., Russo, J., Sun, Y., et al.[2018]

Sipuleucel-T, an autologous immunotherapy, significantly reduced the risk of death by 22% in men with metastatic castration-resistant prostate cancer, leading to a median survival increase of 4.1 months compared to placebo (25.8 months vs. 21.7 months).

While sipuleucel-T improved overall survival, it did not affect the time to disease progression, and common side effects included chills, fever, and headache, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sipuleucel-T immunotherapy for castration-resistant prostate cancer. Kantoff, PW., Higano, CS., Shore, ND., et al.[2023]

The IMbassador250 trial involving 759 men with metastatic castration-resistant prostate cancer found that adding atezolizumab to enzalutamide did not improve overall survival, although it had an acceptable safety profile.

However, patients with high levels of PD-L1 expression and certain immune gene signatures showed longer progression-free survival, suggesting that careful patient selection could enhance the effectiveness of immune checkpoint inhibitors in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Powles, T., Yuen, KC., Gillessen, S., et al.[2023]

Cytokine-based therapies, such as those targeting IL-2, IL-15, and IL-12, offer a promising alternative to traditional T-cell focused immunotherapies for prostate cancer, as they can engage a broader range of immune cells in the tumor microenvironment.

Current strategies using immune checkpoint inhibitors have not improved outcomes in unselected prostate cancer patients, highlighting the need for new approaches that consider the complex interactions of various immune cell types, including natural killer cells and macrophages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signaling new therapeutic opportunities: cytokines in prostate cancer. Chandran, E., Meininger, L., Karzai, F., et al.[2022]

In a study of 32 men with bone-predominant metastatic castration-resistant prostate cancer, the combination of radium-223 and sipuleucel-T led to a significant increase in progression-free survival (39 weeks vs. 12 weeks) and overall survival (not reached vs. 2.6 years) compared to sipuleucel-T alone.

Despite the combination treatment showing lower immune responses (3.2-fold less T-cell response), it resulted in a higher rate of PSA decline (>50% in 31% of patients), suggesting that radium-223 may enhance the clinical effectiveness of sipuleucel-T.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer. Marshall, CH., Fu, W., Wang, H., et al.[2022]

Sipuleucel-T has shown to improve overall survival by 4 months in patients with castration-resistant prostate cancer, particularly benefiting those with favorable prognostic factors like minimal tumor burden and a Gleason score of ≤7.

New immunomodulatory treatments like ipilimumab and tasquinimod, along with antihormonal drugs such as abiraterone acetate, are emerging as promising options for managing castration-resistant prostate cancer, indicating a shift towards more effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for metastatic prostate cancer: do we really need this?]. Heidenreich, A.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Expression of PD-L1 in Hormone-naïve and Treated Prostate Cancer Patients Receiving Neoadjuvant Abiraterone Acetate plus Prednisone and Leuprolide. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Immunotherapeutic Targeting and PET Imaging of DLL3 in Small-Cell Neuroendocrine Prostate Cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Sipuleucel-T immunotherapy for castration-resistant prostate cancer. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Signaling new therapeutic opportunities: cytokines in prostate cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

[Immunotherapy for metastatic prostate cancer: do we really need this?]. [2021]