OncoMatch/Clinical Trials/NCT07016230
Study Investigating Tarlatamab (AMG 757) in Patients With Metastatic/Locally Advanced Small-Cell Lung Cancer (SCLC) and Other Poorly Differentiated Neuroendocrine Carcinomas (NECs), With Biomarker Analysis to Characterize Response/Resistance (UNLOCK TARLATAMAB)
Is NCT07016230 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies Tarlatamab for metastatic/locally advanced small-cell lung cancer.
Treatment: Tarlatamab — UNLOCK TARLATAMAB is an open-label, single arm, multicenter, phase 2 platform study that aims to evaluate the mechanisms of action and resistance to tarlatamab in metastatic/locally advanced Small-Cell Lung Cancer (SCLC) with any level of DLL3 expression and in other poorly differentiated Neuroendocrine Carcinomas (NECs) DLL3 positive. The two cohorts of patients are the following: i. cohort 1: patients with SCLC with any level of DLL3 expression. ii. cohort 2: patients with other poorly differentiated NECs whatever the primary or high grade medullary thyroid carcinoma (MTC, capped at 4 patients) DLL3 positive by immunohistochemistry (IHC). Patients enrolled in both cohorts will receive treatment with tarlatamab at the dose of 1 mg on D1, 10 mg on D8 and D15 and Q2W thereafter in a 28-day cycle. Tarlatamab will be administrated in intravenous route until disease progression, unacceptable toxicity, or consent withdrawal. Tumor and blood samples will be collected at baseline, on-treatment and at progression in order to identify biomarkers of drug response
Check if I qualifyExtracted eligibility criteria
Cancer type
Non-Small Cell Lung Carcinoma
Biomarker criteria
Required: DLL3 any expression (any level)
SCLC with any level of DLL3 expression (Cohort 1)
Required: DLL3 positive (≥1% or H-score ≥1 by IHC) (≥1% or H-score ≥1)
Tumors from Cohort 2 must be DLL3 positive defined as DLL3 ≥1% or H-score ≥1 by IHC
Allowed: TP53 mutation
molecular alterations such as TP53, Rb1, and PTEN
Allowed: RB1 mutation
molecular alterations such as TP53, Rb1, and PTEN
Allowed: PTEN mutation
molecular alterations such as TP53, Rb1, and PTEN
Allowed: RET mutation
RET selective inhibitor if the presence of a RET mutation
Disease stage
Required: Stage IV, III
Metastatic disease required
Grade: high-grade (for MTC and NECs) (IMCGS (for MTC))
metastatic/locally advanced SCLC or other poorly differentiated NECs or high-grade MTC
Performance status
ECOG 0–2(Ambulatory, capable of self-care)
Prior therapy
Must have received: platinum-based chemotherapy
must have been treated with at least 1 line of prior therapy, including a platinum-based regimen (resistant or sensitive to platinum), have experienced progression on standard treatment
Must have received: androgen signaling inhibitor (abiraterone, enzalutamide, darolutamide, apalutamide) — treatment-emergent NEPC
an androgen signaling inhibitor (eg. abiraterone, enzalutamide, darolutamide and/or apalutamide) if treatment-emergent NEPC
Must have received: RET inhibitor — high-grade MTC with RET mutation
must have been treated with at least 1 prior therapy including a RET selective inhibitor if the presence of a RET mutation
Cannot have received: DLL3 inhibitor (tarlatamab)
Prior treatment with tarlatamab or any selective inhibitor of the DLL3 pathway
Lab requirements
Blood counts
Platelet count ≥100,000/mm3; Hemoglobin (Hgb) ≥9.0 g/dL; Absolute neutrophil count (ANC) ≥1500/mm3
Kidney function
Creatinine clearance (CrCl) ≥30 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl; confirmation of CrCl is only required when SCr is >1.5 × ULN
Liver function
AST/ALT and ALP <3 x ULN (or <5 x ULN for patients with liver metastases); Total bilirubin <.5 x ULN (<3 x ULN in the presence of documented Gilbert's Syndrome or <2 X ULN for patients with liver metastases)
Cardiac function
QTcF ≤470 ms for females and ≤450 ms for males; LVEF ≥50% by ECHO or MUGA; no myocardial infarction within 6 months; NYHA ≤ class II within 6 months; no clinically significant pericardial effusion
adequate bone marrow reserve and organ function, based on local laboratory data within 21 days prior to cycle 1, day 1 defined as: Platelet count ≥100 000/mm3...Hgb ≥9.0 g/dL...ANC ≥1500/mm3...CrCl ≥30 mL/min...AST/ALT and ALP <3 x ULN (or <5 x ULN for patients with liver metastases)...Total bilirubin <.5 x ULN (<3 x ULN in the presence of documented Gilbert's Syndrome or <2 X ULN for patients with liver metastases)...Serum albumin ≥2.5 g/dL...PT/INR/aPTT ≤1.5 × ULN except for patients on anticoagulants...QTcF, LVEF, MI, NYHA, pericardial effusion
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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