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)

Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Study ID
NCT07016230
Phase
PHASE2
Status
Recruiting
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Conditions

  • Metastatic/Locally Advanced High-grade MTC
  • Metastatic/Locally Advanced Poorly Differentiated NEC
  • Metastatic/Locally Advanced Small-Cell Lung Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Tarlatamab — DRUG
    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.

Study Details

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

Key Dates

Start date
Jul 2, 2025
Status verified
Nov 2025
Primary completion
Apr 15, 2027
Completion
Jan 15, 2030

Study Design

Enrollment
40 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 1
    patients with metastatic/locally advanced SCLC with any level of DLL3 expression
  • Experimental: Cohort 2
    patients with metastatic/locally advanced other poorly differentiated NECs whatever the primary or high grade medullary thyroid carcinoma (MTC, capped at 4 patients) DLL3 positive by immunohistochemistry (IHC).

Primary Outcome Measure

To estimate the objective response rate (ORR) [ Time Frame: Within the 4 months of treatment initiation ]

Central Contacts