NCT04702737: DeLLpro-300

A Study of AMG 757 in Participants With Neuroendocrine Prostate Cancer

Completed Phase 1 Results posted Last updated 12 September 2025

What this trial tests

Phase 1 trial testing Tarlatamab in Neuroendocrine Prostate Cancer in 41 participants. Completed in 22 July 2024.

Timeline

10 June 2021

Primary endpoint
22 July 2024

22 July 2024

Quick facts

Lead sponsor	Amgen
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	41
Start date	10 June 2021
Primary completion	22 July 2024
Estimated completion	22 July 2024
Sites	21 locations across France, Japan, Netherlands, Belgium, Austria, United Kingdom, Australia, United States

Drugs / interventions tested

• Tarlatamab (TARLATAMAB) — full drug profile →

Conditions studied

• Neuroendocrine Prostate Cancer — all drugs for Neuroendocrine Prostate Cancer →

Sponsor

Amgen — full company profile →

Who can join

18 and older, male only, with Neuroendocrine Prostate Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs) Primary · 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.

Group	Value	95% CI
Tarlatamab Dose Expansion	40

Number of Participants Who Experienced One or More Treatment-related Adverse Events (TRAE) Primary · 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.

Group	Value	95% CI
Tarlatamab Dose Expansion	40

Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Primary · 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 g

Group	Value	95% CI
Tarlatamab Dose Expansion	1

Objective Response Rate (ORR) Secondary · Up to approximately 3 years

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

Group	Value	95% CI
Tarlatamab Dose Expansion	12.0	2.5 – 31.2

Duration of Response (DOR) Secondary · Up to approximately 3 years

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.

Group	Value	95% CI
Tarlatamab Dose Expansion	NA	NA – NA

Radiographic Progression-free Survival (PFS) Secondary · Up to approximately 3 years

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.

Group	Value	95% CI
Tarlatamab Dose Expansion	2.1	1.8 – 3.8

Overall Survival (OS) Secondary · Up to approximately 3 years

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.

Group	Value	95% CI
Tarlatamab Dose Expansion	7.9	4.4 – 13.2

Disease Control Rate (DCR) Secondary · Up to approximately 3 years

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.

Group	Value	95% CI
Tarlatamab Dose Expansion	36.0	18.0 – 57.5

Maximum Serum Concentration (Cmax) of Tarlatamab Secondary · Cycle 2 Day 1 and Day 15: Predose, end of infusion (EOI), 2, 6, 24, 48, 96 and 168 hours after EOI

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.

Cycle 2 Day 1

Group	Value	95% CI
Tarlatamab Dose Expansion	31.1	± 26

Cycle 2 Day 15

Group	Value	95% CI
Tarlatamab Dose Expansion	31.7	± 19

Tarlatamab Concentration at the End of a Dosing Interval or Before Planned Next Dose (Ctrough) Secondary · Cycle 2 Day 15: Predose

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.

Group	Value	95% CI
Tarlatamab Dose Expansion	5.36	± 36

Area Under the Concentration-time Curve Over the Dosing Interval From Time 0 to 336 Hours (AUC336) of Tarlatamab Secondary · Cycle 2 Day 1 and Day 15: Predose, EOI, 2, 6, 24, 48, 96, 168, and 336 hours after EOI

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.

Cycle 2 Day 1

Group	Value	95% CI
Tarlatamab Dose Expansion	4010	± 28

Cycle 2 Day 15

Group	Value	95% CI
Tarlatamab Dose Expansion	4260	± 26

Terminal Phase Elimination Half-life (t1/2,z) of Tarlatamab Secondary · Cycle 2 Day 15: Predose, EOI, 2, 6, 24, 48, 96 and 168 hours after EOI

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.

Group	Value	95% CI
Tarlatamab Dose Expansion	7.23	± 33

Adverse events — posted to ClinicalTrials.gov

Time frame: Death - From enrollment until End of Study (EOS); Median (min, max) was 6.7 (0.1, 37.4) months. TEAE - from 1st study drug until min(last dose + 65 days, EOS); Median (min, max) duration was 3.6 (1.1, 37.3) months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tarlatamab Dose Expansion

Serious: 27/40 (68%)

Deaths: 35/41

Serious adverse events (41 terms)

Reaction	System	Tarlatamab Dose Expansion
Cytokine release syndrome	Immune system disorders	—
Neuroendocrine carcinoma of prostate	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Fatigue	General disorders	—
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Acute kidney injury	Renal and urinary disorders	—
Sepsis	Infections and infestations	—
Neuroendocrine cancer of the prostate metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Atrial flutter	Cardiac disorders	—
Supraventricular tachycardia	Cardiac disorders	—
Tachycardia	Cardiac disorders	—
Dysphagia	Gastrointestinal disorders	—
Large intestine perforation	Gastrointestinal disorders	—
Rectal haemorrhage	Gastrointestinal disorders	—
Stomatitis	Gastrointestinal disorders	—
Pain	General disorders	—
Venoocclusive liver disease	Hepatobiliary disorders	—
Infection	Infections and infestations	—
Pneumonia	Infections and infestations	—
Pneumonia aspiration	Infections and infestations	—
Head injury	Injury, poisoning and procedural complications	—
Hyponatraemia	Metabolism and nutrition disorders	—
Bone pain	Musculoskeletal and connective tissue disorders	—
Immobilisation syndrome	Musculoskeletal and connective tissue disorders	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—

Other adverse events (74 terms — click to expand)

Reaction	System	Tarlatamab Dose Expansion
Cytokine release syndrome	Immune system disorders	—
Decreased appetite	Metabolism and nutrition disorders	—
Constipation	Gastrointestinal disorders	—
Dysgeusia	Nervous system disorders	—
Fatigue	General disorders	—
Pyrexia	General disorders	—
Anaemia	Blood and lymphatic system disorders	—
Nausea	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Headache	Nervous system disorders	—
Diarrhoea	Gastrointestinal disorders	—
Hyponatraemia	Metabolism and nutrition disorders	—
Back pain	Musculoskeletal and connective tissue disorders	—
Urinary retention	Renal and urinary disorders	—
Hypokalaemia	Metabolism and nutrition disorders	—
Abdominal pain	Gastrointestinal disorders	—
Chills	General disorders	—
Urinary tract infection	Infections and infestations	—
Aspartate aminotransferase increased	Investigations	—
Weight decreased	Investigations	—
Tremor	Nervous system disorders	—
Pollakiuria	Renal and urinary disorders	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—
Dyspepsia	Gastrointestinal disorders	—
Asthenia	General disorders	—
Fall	Injury, poisoning and procedural complications	—
Hypophosphataemia	Metabolism and nutrition disorders	—
Myalgia	Musculoskeletal and connective tissue disorders	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Anxiety	Psychiatric disorders	—
Confusional state	Psychiatric disorders	—
Dysuria	Renal and urinary disorders	—
Hypotension	Vascular disorders	—
Sinus tachycardia	Cardiac disorders	—
Tachycardia	Cardiac disorders	—
Oedema peripheral	General disorders	—
COVID-19	Infections and infestations	—
Alanine aminotransferase increased	Investigations	—
Blood creatinine increased	Investigations	—
Electrocardiogram QT prolonged	Investigations	—

Most-reported serious reactions: Cytokine release syndrome, Neuroendocrine carcinoma of prostate, Fatigue, Prostate cancer metastatic, Acute kidney injury, Sepsis, Neuroendocrine cancer of the prostate metastatic, Prostate cancer.

Data from ClinicalTrials.gov NCT04702737 adverse events section.

Sponsor's own description

To evaluate the safety and tolerability of Tarlatamab and will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Notch signaling pathway: architecture, disease, and therapeutics.
   Zhou B, Lin W, Long Y, Yang Y, et al · · 2022 · cited 752× · PMID 35332121 · DOI 10.1038/s41392-022-00934-y
2. Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study.
   Paz-Ares L, Champiat S, Lai WV, Izumi H, et al · · 2023 · cited 221× · PMID 36689692 · DOI 10.1200/jco.22.02823
3. How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer.
   Stultz J, Fong L. · · 2021 · cited 173× · PMID 33820953 · DOI 10.1038/s41391-021-00340-5
4. Molecular events in neuroendocrine prostate cancer development.
   Wang Y, Wang Y, Ci X, Choi SYC, et al · · 2021 · cited 154× · PMID 34290447 · DOI 10.1038/s41585-021-00490-0
5. Current landscape and future directions of bispecific antibodies in cancer immunotherapy.
   Wei J, Yang Y, Wang G, Liu M. · · 2022 · cited 127× · PMID 36389699 · DOI 10.3389/fimmu.2022.1035276
6. Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer.
   Rudin CM, Reck M, Johnson ML, Blackhall F, et al · · 2023 · cited 112× · PMID 37355629 · DOI 10.1186/s13045-023-01464-y
7. Therapy considerations in neuroendocrine prostate cancer: what next?
   Beltran H, Demichelis F. · · 2021 · cited 74× · PMID 34111024 · DOI 10.1530/erc-21-0140
8. DLL3 as an Emerging Target for the Treatment of Neuroendocrine Neoplasms.
   Yao J, Bergsland E, Aggarwal R, Aparicio A, et al · · 2022 · cited 67× · PMID 35983951 · DOI 10.1093/oncolo/oyac161