Actively Recruiting
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)
Led by Gustave Roussy, Cancer Campus, Grand Paris · Updated on 2025-11-26
40
Participants Needed
1
Research Sites
236 weeks
Total Duration
On this page
Sponsors
G
Gustave Roussy, Cancer Campus, Grand Paris
Lead Sponsor
A
Amgen
Collaborating Sponsor
AI-Summary
What this Trial Is About
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
CONDITIONS
Official Title
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)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older
- Diagnosed with metastatic/locally advanced Small-Cell Lung Cancer with any DLL3 expression or other poorly differentiated Neuroendocrine Carcinomas, including high-grade medullary thyroid carcinoma, that are DLL3 positive by immunohistochemistry
- For poorly differentiated NECs, biopsy reviewed by expert pathologist and tumor with Ki67 >20% or mitotic rate >20 per 10 high-power fields
- High-grade medullary thyroid carcinoma defined by international grading system
- Prior treatment with at least one therapy including a platinum-based regimen, with progression after standard treatment
- Patients with neuroendocrine prostate cancer must have prior platinum therapy or androgen signaling inhibitor depending on type
- Patients with high-grade medullary thyroid carcinoma must have prior therapy including RET selective inhibitor if RET mutation present
- Neuroendocrine prostate cancer patients without orchiectomy must remain on LHRH analogue therapy during study
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Minimum life expectancy of 3 months
- At least one measurable tumor lesion by RECIST v1.1
- Tumor site accessible to biopsy and agreement to pre-treatment, on-treatment, and end-of-treatment biopsies
- Adequate bone marrow and organ function by lab tests within 21 days before treatment start
- Baseline oxygen saturation above 90% on room air
- Females of childbearing potential must have negative pregnancy test and agree to effective contraception or abstinence during and 60 days after study
- Female patients must not donate or retrieve ova during and 60 days after treatment
- Male patients must be surgically sterile or use effective birth control during and 60 days after treatment
- Male patients must not donate or freeze sperm during and 60 days after treatment
- Ability to understand and sign informed consent and comply with study procedures
- Affiliation with a Social Security System or beneficiary status
You will not qualify if you...
- Unwilling to participate in biological investigations or provide blood/tissue samples
- Candidates for curative treatment of SCLC, poorly differentiated NECs, or high-grade medullary thyroid carcinoma
- Diagnosed with well-differentiated neuroendocrine tumors, pheochromocytoma, paraganglioma, or low-grade medullary thyroid carcinoma
- Evidence or suspicion of interstitial lung disease or pulmonary fibrosis
- History of recurrent pneumonitis grade 2 or higher or severe immune-related adverse events from immunotherapy
- History of severe allergic reactions to tarlatamab or its ingredients
- Inadequate washout periods from prior therapies or treatments before starting study drug
- Prior treatment with tarlatamab or DLL3 pathway inhibitors
- Active symptomatic brain metastases or spinal cord compression requiring treatment
- Evidence of leptomeningeal disease
- Unresolved toxicities from previous cancer therapies
- Other primary malignancies within 3 years except certain treated skin or in-situ cancers
- Severe or uncontrolled systemic diseases or infections
- Significant pleural effusion unless managed with indwelling catheter
- Uncontrolled cardiovascular diseases including abnormal QT interval, low heart function, recent heart attack, or severe heart failure
- History of arterial thrombosis within 12 months
- Active hepatitis B or C infection unless certain controlled conditions met
- Recent or active COVID-19 infection symptoms within 14 days
- Active or recent autoimmune or inflammatory disorders with exceptions
- Diagnosis of HIV unless on antiviral therapy with undetectable viral load and monitored
- Pregnant or breastfeeding females
- Psychological, social, or geographic conditions that impair study compliance
- Legal incapacity or inability to consent
- Prior severe immune-mediated therapy adverse events
- Participation in another clinical trial with experimental drugs within 30 days or 5 half-lives, whichever is longer
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Gustave Roussy
Villejuif, France
Actively Recruiting
Research Team
Y
Yohann Loriot, MD, PhD
CONTACT
C
Chloé Serhal, PhD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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