Tarlatamab (brand name Imdelltra, code AMG 757) is a bispecific T-cell engager (BiTE) that targets DLL3 on tumor cells and CD3 on T cells, bringing the patient's own T cells into contact with the cancer. It was developed by Amgen and received FDA accelerated approval in June 2024 for extensive-stage small cell lung cancer (ES-SCLC) after platinum-based chemotherapy.

Tarlatamab Clinical Trials (May 2026): 18 Recruiting Interventional Studies

Last updated: May 15, 2026

About Tarlatamab

Drug profile:

Tarlatamab (brand name Imdelltra, code AMG 757) is a bispecific T-cell engager (BiTE) developed by Amgen. One arm binds DLL3 (Delta-like 3, a tumor-cell surface protein highly expressed in neuroendocrine cancers) and the other binds CD3 on T cells, redirecting the patient's own immune effectors against the tumor.

Regulatory status:

FDA accelerated approval (May 2024) for adults with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy, based on the DeLLphi-301 Phase 2 trial. Confirmatory Phase 3 readouts and indication expansions are ongoing.

DLL3 biology:

DLL3 is expressed on the surface of roughly 85% of SCLC tumors and is generally minimal on normal tissues, making it a near-tumor-specific target. DLL3 is also expressed by some extrapulmonary neuroendocrine carcinomas, neuroendocrine prostate cancer (NEPC), Merkel cell carcinoma, and certain neuroendocrine-feature brain tumors.

Active Research Directions in 2026

SCLC frontline combinations — tarlatamab + standard chemo + immunotherapy in untreated ES-SCLC (Phase 3 confirmatory studies)
SCLC post-chemoradiation maintenance — testing whether tarlatamab maintenance after chemo-RT in limited-stage SCLC delays relapse
Subcutaneous formulation — Phase 1 SC tarlatamab to potentially eliminate the inpatient monitoring requirement
Hospital-at-home administration — outpatient delivery models for the step-up dosing phase
Extrapulmonary neuroendocrine carcinoma (NEC) — digestive, pancreatic, prostate NEC; Phase 2/3 trials in pretreated patients
Neuroendocrine prostate cancer (NEPC) — small lineage-defined subset of mCRPC after AR-pathway failure
DLL3-expressing brain tumors — astrocytic, oligodendroglial, glioma + temozolomide
Cross-tumor DLL3 basket — Phase 2 in advanced DLL3-expressing tumors including Merkel cell, large cell neuroendocrine carcinoma, and others
Combination with radiation — RABBIT study (tarlatamab + concurrent RT in DLL3+ tumors)

Recruiting Trials by Indication

Small Cell Lung Cancer (11 trials)

The FDA-approved indication. Trials span first-line combinations, maintenance, pretreated disease, and administration optimization:

NCT07005128 - Tarlatamab + durvalumab + carboplatin + etoposide vs standard chemo-IO in ES-SCLC (Phase 3 frontline)
NCT07242547 - Tarlatamab maintenance after chemo-radiotherapy in limited-stage SCLC (Phase 2)
NCT07203053 - Tarlatamab in pretreated ES-SCLC (Phase 2)
NCT07423585 - Tarlatamab for ES-SCLC (Phase 2)
NCT06830694 - Safety and effectiveness of tarlatamab (AMG 757) in SCLC (Phase 2)
NCT07531095 - Tarlatamab + ZL-1310 ± anti-PD-L1 in SCLC (Phase 1)
NCT07037758 - Tarlatamab + AB248 in ES-SCLC (Phase 1)
NCT06598306 - Subcutaneous tarlatamab in ES-SCLC (Phase 1, novel SC formulation)
NCT07016230 - Tarlatamab in metastatic/locally advanced SCLC and poorly differentiated NEC (Phase 2)
NCT06957314 - Hospital-at-home administration model for tarlatamab patients (outpatient delivery study)

Extrapulmonary Neuroendocrine Carcinoma (NEC)

Neuroendocrine carcinomas of digestive, pancreatic, and other extrapulmonary origin. DLL3 expression is variable; testing required:

NCT06937905 - Tarlatamab vs standard chemotherapy in pre-treated advanced NEC (Phase 3)
NCT07061080 - Tarlatamab in refractory advanced digestive NEC and NEC of unknown primary (Phase 2)
NCT06893783 - Tarlatamab in advanced extrapulmonary NEC (pancreatic, prostate; Phase 2)

Neuroendocrine Prostate Cancer (NEPC)

Lineage-defined subset of metastatic prostate cancer, typically emerging after androgen-receptor pathway failure:

NCT07111507 - Tarlatamab in metastatic prostate cancer with neuroendocrine features (Phase 2)

Brain / CNS Tumors

Selected glioma subtypes and astrocytic/oligodendroglial tumors with DLL3 expression — early-phase exploration:

NCT07243470 - Tarlatamab + temozolomide in adult and childhood CNS tumors (Phase 1/2)
NCT06776250 - Tarlatamab in astrocytic and oligodendroglial brain tumors (Phase 2)

Merkel Cell Carcinoma + Combination with Radiation

Radiation + tarlatamab in DLL3-expressing solid tumors with Merkel cell carcinoma among the listed cohorts:

NCT06814496 - RABBIT study: tarlatamab + concurrent radiation in DLL3-expressing tumors including melanoma, MCC, medullary thyroid, large cell neuroendocrine, others (Phase 1/2)

Pan-DLL3 Basket

Multi-tumor enrollment by DLL3 expression rather than histology:

NCT06788938 - Tarlatamab in advanced DLL3-expressing tumors including neuroendocrine cancers (Phase 2)

Showing all 18 recruiting interventional trials. View the latest on ClinicalTrials.gov.

DLL3 as a Biomarker

Eligibility for most tarlatamab trials does not strictly require pre-confirmed DLL3 positivity for SCLC (DLL3 expression is presumed in ~85% of SCLC). For extrapulmonary indications — NEC, NEPC, MCC, brain tumors — protocols typically require DLL3 immunohistochemistry (IHC) confirmation on archival or fresh tumor tissue. Patients who have not been tested can ask their oncologist whether existing biopsy material can be sent for DLL3 IHC.

Side Effects and Practical Considerations

Cytokine release syndrome (CRS) — the most common notable toxicity, occurring in roughly half of patients. Most events are grade 1–2 and concentrated in the first two doses.
Step-up dosing — cycle 1 day 1 starts at 1 mg, day 8 and day 15 escalate. Designed to mitigate CRS.
Inpatient monitoring — the FDA label requires 22–24 hour inpatient observation after the first two doses. Several open trials (subcutaneous formulation, hospital-at-home) are testing whether this requirement can be relaxed.
Neurotoxicity — including immune effector cell-associated neurotoxicity syndrome (ICANS), generally reversible.
Other immune-related adverse events — less frequent than CRS but possible.

Frequently Asked Questions

What is tarlatamab?

Tarlatamab (brand name Imdelltra, code AMG 757) is a bispecific T-cell engager (BiTE) developed by Amgen. It binds DLL3 on tumor cells and CD3 on T cells, redirecting the patient's own T cells against DLL3-expressing cancers. FDA-approved in 2024 for extensive-stage small cell lung cancer after platinum-based chemotherapy.

Which cancers express DLL3?

DLL3 (Delta-like 3) is most highly expressed in neuroendocrine cancers — roughly 85% of small cell lung cancers, plus variable proportions of extrapulmonary neuroendocrine carcinomas (digestive, pancreatic, prostate), neuroendocrine prostate cancer, Merkel cell carcinoma, and certain neuroendocrine-feature brain tumors. DLL3 IHC testing is the typical eligibility criterion for non-SCLC indications.

What tarlatamab trials are currently recruiting?

There are 18 recruiting interventional tarlatamab trials as of May 2026. The largest cohort is small cell lung cancer (frontline combinations, post-chemoradiation maintenance, pretreated, subcutaneous formulation, hospital-at-home administration). Other indications include extrapulmonary neuroendocrine carcinomas, neuroendocrine prostate cancer, Merkel cell carcinoma, brain tumors, and a pan-DLL3 basket trial.

What are the main side effects of tarlatamab?

The most common notable side effect is cytokine release syndrome (CRS), occurring in roughly half of patients and most often during the first two doses. Tarlatamab is given with step-up dosing on day 1 (1 mg), day 8, and day 15 of cycle 1 to reduce CRS risk, and the FDA label requires 22–24 hour inpatient monitoring after the first two doses. Neurotoxicity (ICANS) and other immune-related adverse events can also occur.

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