Neuroendocrine Prostate CancerPhase 1DeLLpro-300NCT04702737
A Study of AMG 757 in Participants With Neuroendocrine Prostate Cancer
A Phase 1 study testing Tarlatamab in people with Neuroendocrine Prostate Cancer, run by Amgen at 21 sites in 9 countries.
Trial summary
To evaluate the safety and tolerability of Tarlatamab and will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Neuroendocrine Prostate Cancer
- What is being tested?
- Tarlatamab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 21 sitesin 9 countries
- Study dates
- 10 Jun 2021to 22 Jul 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria (Part 1: Dose Exploration and Part 2: Dose Expansion):
- Participant has provided informed consent prior to initiation of any study specific activities/procedures.
- Men aged ≥ 18 years at time of signing the informed consent.
- Metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC) defined by histology, immunohistochemistry, or genomic analyses of baseline tumor tissue (by local assessment) or circulating tumor DNA (ctDNA) (by local assessment) as per protocol
- At least 1 line of prior systemic treatment per protocol.
- Participants with treatment-emergent NEPC or de novo NEPC with histologic evidence of prostate cancer with neuroendocrine differentiation without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analogue therapy during the course of protocol therapy
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Prostate Cancer Working Group 3 (PCWG3) modifications
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- Participants with treated brain metastases are eligible provided they meet defined criteria
- Adequate organ function as defined in protocol
Exclusion Criteria (Part 1: Dose Exploration and Part 2: Dose Expansion):
- History of other malignancy within the past 2 years, with exceptions:
- Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before enrollment and felt to be at low risk for recurrence by the treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated non-muscle invasive urothelial carcinoma
- History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥ 2 years
- Untreated or symptomatic brain metastases and leptomeningeal disease
- Anti-tumor therapy within 28 days of study day 1; concurrent use of hormone deprivation therapy for hormone refractory prostate cancer is permitted; participants on a stable bisphosphonate or denosumab prior to study day 1 are eligible
Exceptions:
- Participants who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicities have resolved to Grade ≤ 1
- Prior palliative radiotherapy must have been completed at least 7 days before the first dose of tarlatamab
- Participants who received androgen signaling inhibitor are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to Grade ≤ 1
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior study day 1
- Active autoimmune disease requiring systemic treatment within the past 2 years
- Known positive test for human immunodeficiency virus (HIV) or hepatitis
- Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1 (with the exception of alopecia or toxicities that are stable and well-controlled)
- History of hypophysitis or pituitary dysfunction
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Participants on prior delta-like ligand 3 (DLL3)-targeted therapy may be eligible if discussed with Amgen Medical Monitor prior to enrollment
- Evidence of severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection unless agreed upon with Medical Monitor and with no acute symptoms of coronavirus disease 2019 (COVID19) disease within 14 days prior to first dose of investigational product (counted from day of positive test for asymptomatic participants).
Trial locations and contacts
21 sites in 9 countries.
21 sites in 9 countries
United States10 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
University of Chicago
Chicago, Illinois, 60637
The Ohio State University
Columbus, Ohio, 43210
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Community Health Network MD Anderson Cancer Center - North
Indianapolis, Indiana, 46250
Weill Cornell Medical College
New York, New York, 10021
Mayo Clinic Arizona
Phoenix, Arizona, 85054
University of California at San Francisco Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Washington University
St Louis, Missouri, 63110-1093
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27103
Austria3 sites
Medizinische Universitaet Graz
Graz, 8036
Ordensklinikum Linz Elisabethinen
Linz, 4020
Landeskrankenhaus Salzburg
Salzburg, 5020
Australia2 sites
Chris OBrien Lifehouse
Camperdown, New South Wales, 2050
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Spain1 site
Hospital Clinic i Provincial de Barcelona
Barcelona, Catalonia, 08036
About this study
Official title: A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of Delta-like Protein 3 Half-life Extended Bispecific T-cell Engager AMG 757 in Subjects With De Novo or Treatment Emergent Neuroendocrine Prostate Cancer
To evaluate the safety and tolerability of Tarlatamab and will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).
- Conditions
- Neuroendocrine Prostate Cancer
- Being tested
- Tarlatamab
- Keywords
- De novo or treatment emergent neuroendocrine prostate cancer, Non-canonical Notch ligand
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TarlatamabDrug
Also called AMG 757
Tarlatamab will be administered as an intravenous (IV) infusion.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Dose Exploration | Experimental | 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. Receives: Drug: Tarlatamab |
| Part 2: Dose Expansion | Experimental | Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study. Receives: Drug: Tarlatamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an AE starting on or after the first dose of tarlatamab, and up to and including 47 days after the last dose of tarlatamab excluding the events reported after End of Study date. Clinically significant changes from baseline in vital signs, 12-lead electrocardiograms (ECGs) and clinical laboratory tests were also reported as TEAEs.
Measured: Up to approximately 3 years
Number of Participants Who Experienced One or More Treatment-related Adverse Events (TRAE)
A TRAE was defined as a TEAE that per investigator review had a reasonable possibility of being caused by tarlatamab. Clinically significant changes from baseline in vital signs, 12-lead ECGs and clinical laboratory tests were also reported as TEAEs.
Measured: Up to approximately 3 years
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
A DLT was defined as any qualifying toxicity that was at least possibly related to tarlatamab with an onset within the first 28 days following first dose with either of the following criteria:
- Grade 3 adverse event lasting more than 3 days (with the exception of fatigue and Grade 3 non-febrile neutropenia that improved to ≤ Grade 1 within 3 weeks including the use of growth factor support per neutropenia management guidelines);
- ≥ Grade 4 adverse event regardless of duration (with the exception of grade 4 non-febrile neutropenia lasting less than or equal to 7 days including the use of growth factor support per neutropenia management guidelines).
Measured: Up to 28 days
Secondary outcomes (9)
Objective Response Rate (ORR)
OR was assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications. OR was defined as best overall response of partial response (PR) or complete response (CR) per RECIST 1.1, confirmed by an assessment at least 4 weeks later. Participants who did not experience a PR/CR or did not have any follow-up tumor assessments were regarded as non-responders. ORR was defined as the percentage of participants with a best overall response of confirmed CR or PR per RECIST 1.1. The percentage of participants with an OR was summarized along with the Clopper-Pearson (Clopper and Pearson, 1934) exact 95% confidence interval (CI). The result reported was evaluated by central reviewer assessment.
Measured: Up to approximately 3 years
Duration of Response (DOR)
DOR was defined as the time from the date of an initial objective response to the earlier of progressive disease or death for participants with an objective response per RECIST 1.1. DOR was assessed per RECIST 1.1 with PCWG3 modifications. The distribution of DOR was summarized using the Kaplan-Meier (KM) method with CI calculated using the Brookmeyer and Crowley (Brookmeyer and Crowley, 1982) method. The result reported was evaluated by central reviewer assessment.
Measured: Up to approximately 3 years
Radiographic Progression-free Survival (PFS)
Radiographic PFS was defined as the interval from the first dose of tarlatamab to the earlier of a radiographic progression or death from any cause. Radiographic PFS was assessed per RECIST 1.1 with PCWG3 modifications. The distribution of radiographic PFS was summarized using the KM method with CI calculated using the Brookmeyer and Crowley (Brookmeyer and Crowley, 1982) method. The result reported was evaluated by central reviewer assessment.
Measured: Up to approximately 3 years
Overall Survival (OS)
OS was defined as the time from the start of treatment until event of death due to any cause. The distribution of OS was summarized using the KM method with CI calculated using the Brookmeyer and Crowley (Brookmeyer and Crowley, 1982) method.
Measured: Up to approximately 3 years
Disease Control Rate (DCR)
DCR was defined as the percentage of participants with a best overall response of confirmed response (CR/PR) or stable disease (SD) as per RECIST 1.1. The DCR was assessed per RECIST 1.1. The percentage of participants with disease control with corresponding exact 95% CI was calculated using the Clopper-Pearson (Clopper and Pearson, 1934) method. The result reported was evaluated by central reviewer assessment.
Measured: Up to approximately 3 years
Maximum Serum Concentration (Cmax) of Tarlatamab
Pharmacokinetic (PK) parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.
Measured: Cycle 2 Day 1 and Day 15: Predose, end of infusion (EOI), 2, 6, 24, 48, 96 and 168 hours after EOI
Tarlatamab Concentration at the End of a Dosing Interval or Before Planned Next Dose (Ctrough)
PK parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. The result for this endpoint is given for cycle 2 only.
Measured: Cycle 2 Day 15: Predose
Area Under the Concentration-time Curve Over the Dosing Interval From Time 0 to 336 Hours (AUC336) of Tarlatamab
PK parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. The result for this endpoint is given for cycle 2 only.
Measured: Cycle 2 Day 1 and Day 15: Predose, EOI, 2, 6, 24, 48, 96, 168, and 336 hours after EOI
Terminal Phase Elimination Half-life (t1/2,z) of Tarlatamab
PK parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. The result for this endpoint is given for cycle 2 only.
Measured: Cycle 2 Day 15: Predose, EOI, 2, 6, 24, 48, 96 and 168 hours after EOI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2021
- Study start10 Jun 2021
- Primary completion22 Jul 2024
- Study completion22 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuroendocrine Prostate CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04702737
- Sponsor's protocol ID
- 20200040
- Acronym
- DeLLpro-300
- Status last verified
- Aug 2025
- First submitted
- 7 Jan 2021
- Last updated
- 12 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
- Expanded access
- Available
Publications
Aggarwal R, Rottey S, Bernard-Tessier A, Mellado B, Kosaka T, Stadler WM, Horvath L, Greil R, O'Neil B, Siddiqui BA, Bauernhofer T, Bilen MA, Eskens F, Sandhu S, Shaw C, Ju CH, Decato BE, Yu B, Aparicio A. 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;31(18):3854-3863. doi: 10.1158/1078-0432.CCR-25-1211.
PubMed 40689871
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of Delta-like Protein 3 Half-life Extended Bispecific T-cell Engager AMG 757 in Subjects With De Novo or Treatment Emergent Neuroendocrine Prostate Cancer
- ClinicalTrials.gov ID
- NCT04702737
- Acronym / sponsor ID
- DeLLpro-300 / 20200040
- Conditions
- Neuroendocrine Prostate Cancer
- Keywords
- De novo or treatment emergent neuroendocrine prostate cancer, Non-canonical Notch ligand
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 10 Jun 2021 (actual)
- Primary completion
- 22 Jul 2024 (actual)
- Study completion
- 22 Jul 2024 (actual)
- First posted
- 11 Jan 2021 (actual)
- Results
- Posted 12 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety and tolerability of Tarlatamab and will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1: Dose Exploration | Experimental | Drug: TarlatamabThe 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. |
| Part 2: Dose Expansion | Experimental | Drug: TarlatamabParticipants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TarlatamabAlso: AMG 757Tarlatamab will be administered as an intravenous (IV) infusion. | Drug | Part 1: Dose Exploration, Part 2: Dose Expansion |
Primary outcome
Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to approximately 3 years
An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an AE starting on or after the first dose of tarlatamab, and up to and including 47 days after the last dose of tarlatamab excluding the events reported after End of Study date. Clinically significant changes from baseline in vital signs, 12-lead electrocardiograms (ECGs) and clinical laboratory tests were also reported as TEAEs.
Number of Participants Who Experienced One or More Treatment-related Adverse Events (TRAE)
Time frame: Up to approximately 3 years
A TRAE was defined as a TEAE that per investigator review had a reasonable possibility of being caused by tarlatamab. Clinically significant changes from baseline in vital signs, 12-lead ECGs and clinical laboratory tests were also reported as TEAEs.
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
Time frame: Up to 28 days
A DLT was defined as any qualifying toxicity that was at least possibly related to tarlatamab with an onset within the first 28 days following first dose with either of the following criteria: 1. Grade 3 adverse event lasting more than 3 days (with the exception of fatigue and Grade 3 non-febrile neutropenia that improved to ≤ Grade 1 within 3 weeks including the use of growth factor support per neutropenia management guidelines); 2. ≥ Grade 4 adverse event regardless of duration (with the exception of grade 4 non-febrile neutropenia lasting less than or equal to 7 days including the use of growth factor support per neutropenia management guidelines).
9 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to approximately 3 years
Duration of Response (DOR)
Time frame: Up to approximately 3 years
Radiographic Progression-free Survival (PFS)
Time frame: Up to approximately 3 years
Overall Survival (OS)
Time frame: Up to approximately 3 years
Disease Control Rate (DCR)
Time frame: Up to approximately 3 years
Maximum Serum Concentration (Cmax) of Tarlatamab
Time frame: Cycle 2 Day 1 and Day 15: Predose, end of infusion (EOI), 2, 6, 24, 48, 96 and 168 hours after EOI
Tarlatamab Concentration at the End of a Dosing Interval or Before Planned Next Dose (Ctrough)
Time frame: Cycle 2 Day 15: Predose
Area Under the Concentration-time Curve Over the Dosing Interval From Time 0 to 336 Hours (AUC336) of Tarlatamab
Time frame: Cycle 2 Day 1 and Day 15: Predose, EOI, 2, 6, 24, 48, 96, 168, and 336 hours after EOI
Terminal Phase Elimination Half-life (t1/2,z) of Tarlatamab
Time frame: Cycle 2 Day 15: Predose, EOI, 2, 6, 24, 48, 96 and 168 hours after EOI
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40689871Aggarwal R, Rottey S, Bernard-Tessier A, Mellado B, Kosaka T, Stadler WM, Horvath L, Greil R, O'Neil B, Siddiqui BA, Bauernhofer T, Bilen MA, Eskens F, Sandhu S, Shaw C, Ju CH, Decato BE, Yu B, Aparicio A. 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;31(18):3854-3863. doi: 10.1158/1078-0432.CCR-25-1211.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
21 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tarlatamab in people with Neuroendocrine Prostate Cancer, run by Amgen at 21 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Austria, Australia, Belgium, France and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) (time frame: Up to approximately 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04702737, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2025.