Tarlatamab for Prostate Cancer

(DeLLpro-300 Trial)

No longer recruiting at 25 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies a new treatment called Tarlatamab, an experimental drug, to assess its safety and determine the optimal dose for treating metastatic prostate cancer. The trial consists of two parts: first, it explores different doses, and then it tests the best dose identified. Men with a specific type of prostate cancer that has neuroendocrine features—cancer cells that look and act differently—and who have already undergone other treatments might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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 there any evidence suggesting that Tarlatamab is likely to be safe for humans?

In earlier studies, tarlatamab has shown signs of safety for people. One study found that tarlatamab did not cause any new safety issues, meaning there were no unexpected side effects. Another study showed that tarlatamab was well-tolerated, with most patients handling the treatment without major problems.

These findings are encouraging, especially since this trial remains in the early stages. Researchers are still determining the safest dose, but current evidence suggests that tarlatamab is reasonably safe to try. ^{1 2 3 4 5}

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

Researchers are excited about Tarlatamab for prostate cancer because it offers a unique approach compared to traditional treatments like hormone therapy, chemotherapy, or surgery. Unlike these standard options, Tarlatamab is an investigational bispecific T-cell engager (BiTE) antibody construct. It is designed to redirect and activate the body's immune system specifically against prostate cancer cells by targeting a protein called DLL3, which is often overexpressed in these cancer cells. This targeted mechanism has the potential to improve treatment efficacy and minimize side effects, offering new hope for patients with prostate cancer.

What evidence suggests that Tarlatamab might be an effective treatment for prostate cancer?

Research has shown that Tarlatamab has promising effects in treating neuroendocrine prostate cancer (NEPC), particularly in tumors with DLL3 positivity. Specifically, Tarlatamab helped about 22.2% of patients with these tumors, with nearly a quarter experiencing a reduction in their cancer. Those who responded to the treatment saw benefits lasting between 5.5 and 25.8 months. The trial will explore Tarlatamab in two parts: Part 1 will focus on dose exploration to estimate the maximum tolerated dose (MTD), and Part 2 will expand on this by administering the recommended phase 2 dose (RP2D) identified in Part 1. These early results suggest that Tarlatamab could be effective for certain types of prostate cancer, but more research is needed to confirm these findings. ^{1 6 7 8 9}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

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.

My prostate cancer can be measured by specific medical criteria.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40689871/

Results from the Phase 1b DeLLpro-300 Study The DeLLpro-300 study provides preliminary evidence for the safety and antitumor activity of tarlatamab in DLL3+ NEPC.

2. onclive.com onclive.com/view/tarlatamab-demonstrates-early-safety-and-activity-in-dll3-neuroendocrine-prostate-cancer

Tarlatamab Demonstrates Early Safety and Activity in ... Tarlatamab showed a 10.5% objective response rate in NEPC, with better outcomes in DLL3-positive tumors, achieving a 22.2% response rate. Common ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-25-1211/763701/Safety-and-Efficacy-of-Tarlatamab-in-patients-with?searchresult=1

Safety and Efficacy of Tarlatamab in Patients with ... The DeLLpro-300 study provides preliminary evidence for the safety and antitumor activity of tarlatamab in DLL3+ NEPC. Translational Relevance.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04702737

NCT04702737 | A Study of AMG 757 in Participants With ... Safety and Efficacy of Tarlatamab in Patients with Neuroendocrine Prostate Cancer: Results from the Phase 1b DeLLpro-300 Study. Clin Cancer Res. 2025 Sep 15 ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5012

Phase 1b study of tarlatamab in de novo or treatment- ... As of 24 January 2024, ORR in DLL3+ pts was 22.2% (95% CI, 6.4, 47.6); durations of response in the 4 pts with response were 25.8 m, 9.2 m, 5.5 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12434391/

Results from the Phase 1b DeLLpro-300 Study - PMC In this phase 1b DeLLpro-300 study of NEPC, tarlatamab 100 mg administered intravenously every 2 weeks with one-step dosing demonstrated no new safety signals ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04702737

NCT04702737 | A Study of AMG 757 in Participants With ... To evaluate the safety and tolerability of Tarlatamab and will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).

8. clin.larvol.com clin.larvol.com/trial-detail/NCT04702737

A Study of AMG 757 in Participants With Neuroendocrine ... Clin Cancer Res 2025 - Safety and Efficacy of Tarlatamab in patients with Neuroendocrine Prostate Cancer: Results from the Phase 1b DeLLpro-300 Study.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.TPS197

Phase 1b study of tarlatamab, a half-life extended ... Tarlatamab is a DLL3-targeting HLE BiTE immune therapy designed to bind DLL3 on cancer cells and CD3 on T cells, resulting in T cell activation and expansion.