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, received FDA accelerated approval in May 2024, and was granted full (traditional) FDA approval on November 19, 2025 for adults with extensive-stage small cell lung cancer (ES-SCLC) that has progressed on or after platinum-based chemotherapy, based on the Phase 3 DeLLphi-304 trial (median overall survival 13.6 vs 8.3 months versus chemotherapy, a 40% reduction in risk of death).

Tarlatamab Clinical Trials (June 2026, Post-ASCO 2026): 18 Recruiting Interventional Studies

Last updated: June 9, 2026 — refreshed post-ASCO 2026 (June 5–9, Chicago)

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 in May 2024 (based on the Phase 2 DeLLphi-301 trial) was converted to full (traditional) FDA approval on November 19, 2025 for adults with extensive-stage small cell lung cancer (ES-SCLC) that has progressed on or after platinum-based chemotherapy. The conversion was based on the Phase 3 DeLLphi-304 confirmatory trial, which showed median overall survival of 13.6 vs 8.3 months versus standard chemotherapy — a 40% reduction in the risk of death. The NCCN Small Cell Lung Cancer guidelines now list tarlatamab as the only Category 1 preferred option for second-line ES-SCLC after platinum chemotherapy.

What changed at ASCO 2026:

Tarlatamab matured at this year's meeting from "second-line salvage in SCLC" toward maintenance, frontline, and beyond SCLC. Key trials anchoring this expansion: DeLLphi-312 in untreated 1L ES-SCLC (NCT07005128, Phase 3), DeLLphi-308 subcutaneous formulation (NCT06598306, Phase 1), DeLLphi-311 + AB248 CD8-selective IL-2 (NCT07037758, Phase 1), a Phase 3 vs chemotherapy in pretreated extrapulmonary neuroendocrine carcinoma (NCT06937905), and the TARGID Phase 2 in recurrent IDH-mutant glioma (NCT06776250). See our ASCO 2026 wrap-up (takeaway #5) for the patient-facing summary.

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, large cell neuroendocrine carcinoma, and a subset of IDH-mutant astrocytic and oligodendroglial brain tumors (the population enrolled in the TARGID study).

Active Research Directions in 2026 (Post-ASCO Update)

SCLC frontline combinations (DeLLphi-312) — tarlatamab + durvalumab + carboplatin + etoposide vs durvalumab + chemo in untreated 1L ES-SCLC (NCT07005128, Phase 3)
SCLC post-chemoradiation maintenance — tarlatamab maintenance after chemo-radiotherapy in limited-stage SCLC (NCT07242547, Phase 2)
Subcutaneous formulation (DeLLphi-308) — Phase 1b SC tarlatamab in ES-SCLC; aims to eliminate the FDA-mandated 22–24h inpatient monitoring for the first two doses, the main operational bottleneck for tarlatamab adoption
Hospital-at-home administration (MATCHES-Novel) — telehealth/outpatient delivery model for the step-up dosing phase (NCT06957314)
Combination with CD8-selective IL-2 (DeLLphi-311) — tarlatamab + AB248 (etakafusp alfa) in ES-SCLC (NCT07037758, Phase 1)
Extrapulmonary NEC — first 2L standard candidate — Phase 3 of tarlatamab vs investigator-choice chemotherapy in pretreated pulmonary or gastroenteropancreatic NEC (NCT06937905). EP-NEC patients currently have no second-line standard.
EP-NEC Phase 2 (DeLLight) — tarlatamab in pancreatic and prostate NEC (NCT06893783)
Neuroendocrine / DLL3-positive prostate cancer (TIDAL) — Phase 2 in DLL3+ metastatic prostate cancer (NCT07111507)
IDH-mutant brain tumors (TARGID) — Phase 2 in recurrent/refractory IDH-mutant astrocytoma and oligodendroglioma (NCT06776250). Tests intracranial activity of the DLL3 BiTE.
Combination with radiation (RABBIT) — tarlatamab + concurrent RT in DLL3-expressing tumors (NCT06814496, Phase 1/2)
Pan-DLL3 basket — Phase 2 in advanced DLL3-expressing tumors including neuroendocrine neoplasms (NCT06788938)

Recruiting Trials by Indication

Small Cell Lung Cancer (10 trials)

The FDA-approved indication (full approval Nov 19, 2025; NCCN Category 1 preferred 2L). Trials span first-line combinations, maintenance after chemo-RT, pretreated disease, and administration optimization (SubQ formulation, hospital-at-home):

NCT07005128 — DeLLphi-312: tarlatamab + durvalumab + carboplatin + etoposide vs durvalumab + carboplatin + etoposide in untreated 1L ES-SCLC (Phase 3, the frontline combination question)
NCT07242547 — Tarlatamab maintenance after chemo-radiotherapy in limited-stage SCLC (Phase 2)
NCT07203053 — Tarlatamab in pretreated ES-SCLC, ECOG performance status 2 (Phase 2; the underrepresented frail-patient cohort)
NCT07423585 — Tarlatamab for ES-SCLC (Phase 2)
NCT06830694 — Tarlatamab + etoposide + carboplatin + atezolizumab in EGFR-TKI-treated adenocarcinoma transformed to SCLC (Phase 2)
NCT07531095 — Tarlatamab + ZL-1310 (DLL3-targeted ADC) ± anti-PD-L1 in SCLC (Phase 1)
NCT07037758 — DeLLphi-311: tarlatamab + AB248 (etakafusp alfa, CD8-selective IL-2) in ES-SCLC (Phase 1b)
NCT06598306 — DeLLphi-308: subcutaneous tarlatamab in ES-SCLC (Phase 1b; a SubQ formulation that could eliminate the inpatient observation for the first two doses)
NCT07016230 — UNLOCK TARLATAMAB: tarlatamab in metastatic/locally advanced SCLC and poorly differentiated NEC with biomarker response/resistance analysis (Phase 2)
NCT06957314 — MATCHES-Novel: hospital-at-home telehealth delivery model for tarlatamab patients (the operational pilot for outpatient administration)

Extrapulmonary Neuroendocrine Carcinoma (EP-NEC, 3 trials)

Poorly differentiated neuroendocrine carcinomas of digestive, pancreatic, prostate, and other extrapulmonary origin. EP-NEC patients currently have no second-line standard of care; the Phase 3 below is the most consequential indication expansion presented at ASCO 2026:

NCT06937905 — Tarlatamab vs investigator-choice chemotherapy in pretreated advanced pulmonary or gastroenteropancreatic poorly differentiated NEC (Phase 3; the first 2L EP-NEC standard candidate)
NCT07061080 — Tarlatamab in refractory advanced digestive NEC and NEC of unknown primary (Phase 2)
NCT06893783 — DeLLight: tarlatamab in advanced extrapulmonary NEC including pancreatic and prostate NEC (Phase 2)

DLL3-Positive / Neuroendocrine Prostate Cancer (1 trial)

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

NCT07111507 — TIDAL: tarlatamab in DLL3-positive metastatic prostate cancer (Phase 2)

Brain / CNS Tumors (2 trials)

DLL3-expressing brain tumors are the newest frontier. The TARGID study is the first to test the DLL3 BiTE's intracranial activity in a defined molecular glioma subset (IDH-mutant), where standard salvage options after recurrence are limited:

NCT06776250 — TARGID: tarlatamab in recurrent/refractory IDH-mutant astrocytoma and oligodendroglioma (Phase 2)
NCT07243470 — Tarlatamab + metronomic temozolomide in adolescent and adult high-grade brain tumors (Phase 1/2)

Combination with Radiation — RABBIT (1 trial)

Concurrent radiation + tarlatamab in DLL3-expressing solid tumors. The cohort spans large cell neuroendocrine carcinoma of the lung, Merkel cell carcinoma, medullary thyroid, sinonasal undifferentiated carcinoma, esthesioneuroblastoma, glioblastoma, and others:

NCT06814496 — RABBIT: tarlatamab + concurrent radiation therapy in tumors with high prevalence of DLL3 (Phase 1/2)

Pan-DLL3 Basket (1 trial)

Multi-tumor enrollment defined by DLL3 expression rather than histology:

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

Showing all 18 recruiting interventional trials, corpus-verified June 9, 2026 against the ClinTrialFinder corpus. 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; the TIDAL prostate study (NCT07111507) explicitly enrolls a DLL3-positive cohort. 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. Granted FDA accelerated approval in May 2024 and converted to full (traditional) FDA approval on November 19, 2025 for adults with extensive-stage small cell lung cancer (ES-SCLC) that has progressed on or after platinum-based chemotherapy. The conversion was based on the Phase 3 DeLLphi-304 confirmatory trial, which showed median overall survival of 13.6 vs 8.3 months versus standard chemotherapy — a 40% reduction in the risk of death.

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, large cell neuroendocrine carcinoma, and a subset of IDH-mutant astrocytic and oligodendroglial brain tumors (the population in the TARGID Phase 2 study, NCT06776250). 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 June 2026 (post-ASCO 2026). The largest cohort is small cell lung cancer, including: DeLLphi-312 frontline tarlatamab + durvalumab + chemo in 1L ES-SCLC (NCT07005128, Phase 3); DeLLphi-308 subcutaneous formulation (NCT06598306); DeLLphi-311 + AB248 CD8-selective IL-2 (NCT07037758); maintenance after chemo-RT in limited-stage SCLC (NCT07242547); and the MATCHES-Novel hospital-at-home delivery model (NCT06957314). Beyond SCLC: a Phase 3 vs chemotherapy in pretreated extrapulmonary NEC (NCT06937905, the first 2L EP-NEC standard candidate); the DeLLight Phase 2 in EP-NEC (NCT06893783); the RABBIT tarlatamab + radiation study (NCT06814496); the TARGID Phase 2 in IDH-mutant glioma (NCT06776250); and the TIDAL Phase 2 in DLL3-positive metastatic prostate cancer (NCT07111507).

What is NCCN's current recommendation for tarlatamab?

Following the November 19, 2025 FDA full approval based on DeLLphi-304, the NCCN Small Cell Lung Cancer guidelines list tarlatamab as the only Category 1 preferred treatment option for second-line extensive-stage SCLC after platinum-based chemotherapy. Category 1 means the recommendation is based on high-level evidence with uniform NCCN consensus.

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. The DeLLphi-308 subcutaneous formulation (NCT06598306) and the MATCHES-Novel hospital-at-home delivery study (NCT06957314) are testing whether this inpatient observation can be relaxed. Neurotoxicity (ICANS) and other immune-related adverse events can also occur.

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