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New treatment option for Metastatic/Locally Advanced Small-Cell Lung Cancer
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)
ClinicalTrials.gov ID: NCT07016230
What this study is testing
What is Tarlatamab?
Tarlatamab is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for metastatic/locally advanced small-cell lung cancer.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Age ≥18 years
- Patients with histologically confirmed diagnosis of metastatic/locally advanced SCLC with any level of DLL3 expression (Cohort 1) or other poorly...
- For patients with poorly differentiated NECs whatever the primary, the biopsy of the disease diagnosis should be reviewed by an expert pathologist...
- High-grade MTC should be defined according to international medullary cancer grading system (IMCGS)
- Patients with metastatic/locally advanced SCLC and other poorly differentiated NECs must have been treated with at least 1 line of prior therapy...
You likely can't join if
- Patients unwilling to participate to the biological investigations and to perform blood and tissue sample collection as required in the protocol
- Patients with SCLC or other poorly differentiated NECs whatever the primary or high-grade MTC amenable for treatment with curative intent
- Patients with well differentiated neuroendocrine tumors, whatever the grade, pheocromocytoma, paraganglyoma, or low grade MTC
- Patients with evidence of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis) or is suspected to have such...
- Patients who experienced recurrent pneumonitis (grade 2 or higher) or severe, life-threatening immune-mediated AEs or infusion-related reactions...
- Patients with a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients of tarlatamab
See the full eligibility criteria
Who can join
- Age ≥18 years
- Patients with histologically confirmed diagnosis of metastatic/locally advanced SCLC with any level of DLL3 expression (Cohort 1) or other poorly differentiated NECs whatever the primary or high-grade MTC (Cohort 2)...
- For patients with poorly differentiated NECs whatever the primary, the biopsy of the disease diagnosis should be reviewed by an expert pathologist. Large cell, small cell or not otherwise specified are eligible. In...
- High-grade MTC should be defined according to international medullary cancer grading system (IMCGS)
- Patients with metastatic/locally advanced SCLC and other poorly differentiated NECs must have been treated with at least 1 line of prior therapy, including a platinum-based regimen (resistant or sensitive to platinum)...
- Patients with NEPC and without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analogue therapy during the course of protocol therapy
- Patients must have an ECOG performance status ≤2 at the time of screening
- Patients must have a minimum life expectancy of 3 months
- Patients must have at least one radiologically measurable lesion according to response evaluation criteria in solid tumors (RECIST) v1.1 criteria
- Patients must have a tumor site easily accessible to biopsy, avoiding bone biopsy when possible. Patient must have accepted to perform pre-treatment, on-treatment, and end-of-treatment tumor and blood biopsies
- Patients must have 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 or ≥100 × 109/L (platelet transfusions are not allowed up to 14 days prior to cycle 1 Day 1 to meet eligibility)
- Hemoglobin (Hgb) ≥9.0 g/dL (transfusion and/or growth factor support is allowed)
- Absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5 × 109/L (use of growth factors is not allowed in the 14 days prior cycle 1)
- Creatinine clearance (CrCl): 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
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and alkaline phosphatase (ALP) \<3 x ULN (or \<5 x ULN for patients with liver metastases)
- Total bilirubin (TBL) \<.5 x ULN (\<3 x ULN in the presence of documented Gilbert's Syndrome [unconjugated hyperbilirubinemia]) or \<2 X ULN for patients with liver metastases
- Serum albumin ≥2.5 g/dL
- Prothrombin time (PT) or Prothrombin time- international normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)/partial thromboplastin time (PTT)≤1.5 × (ULN), except for patients on...
- Patients must have baseline oxygen saturation \> 90% on room air
- Females of reproductive/childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the...
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- Oral
- Intravaginal
- Transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation:
- Oral
- Injectable
- Implantable
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner
- Complete sexual abstinence defined as refraining from heterosexual intercourse during and upon completion of the study and for at least 7 months for females after the last dose of study drug. Periodic abstinence...
- Female patients must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 60 days after the final study drug administration
- Male patients must be surgically sterile or must withhold heterosexual intercourse or must be willing to use a highly effective birth control upon enrollment, during the treatment period, and for at least 60 days...
- Male patients must not freeze or donate sperm starting at screening and throughout the study period, and at least 60 days after the final study drug administration
- Patients must understand, sign and date the written informed consent from prior to any protocol-specific procedures performed. Patients should be able and willing to comply with study visits and procedures as per...
- Patients must be affiliated to a Social Security System or beneficiary of the same
What rules you out
- Patients unwilling to participate to the biological investigations and to perform blood and tissue sample collection as required in the protocol
- Patients with SCLC or other poorly differentiated NECs whatever the primary or high-grade MTC amenable for treatment with curative intent
- Patients with well differentiated neuroendocrine tumors, whatever the grade, pheocromocytoma, paraganglyoma, or low grade MTC
- Patients with evidence of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis) or is suspected to have such disease by imaging during screening
- Patients who experienced recurrent pneumonitis (grade 2 or higher) or severe, life-threatening immune-mediated AEs or infusion-related reactions including those that lead to permanent discontinuation while on treatment...
- Patients with a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients of tarlatamab
- Inadequate washout period prior to cycle 1 day 1, defined as:
- Whole brain radiation therapy or stereotactic brain radiation therapy \<14 days
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation \<28 days or palliative radiation therapy \<7 days
- Any investigational agents or other anticancer drug(s) from a previous cancer treatment regimen or clinical study \<30 days or \< 5 half-lives, whichever is longer, prior to first dose of tarlatamab. Conventional...
- Major surgery (excluding placement of vascular access) \< 21 days
- Live virus and live-attenuated vaccination \<28 days
- Systemic steroid therapy or other immunosuppressive therapy \< 7 days
- Prior treatment with tarlatamab or any selective inhibitor of the DLL3 pathway
- Evidence of spinal cord compression or brain metastases, defined as being clinically active and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Patients with...
- Patients with evidence of any leptomeningeal disease
- Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to grade 1 or baseline according to the NCI-CTCAE v5.0
- Any evidence of primary malignancy other than metastatic/locally advanced SCLC, poorly differentiated NEC or high-grade MTC within 3 years prior to cycle 1 day 1, except adequately resected non-melanoma skin cancer...
- Any evidence of severe or uncontrolled systemic diseases including active bleeding diatheses, active infection, psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the...
- Patients with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of study treatment.
- Patients with clinically significant pleural effusion will be excluded. Pleural effusion managed with indwelling pleural catheter (eg, PleurX) are allowed
- Uncontrolled or significant cardiovascular disease prior to cycle 1 day 1, including:
- Corrected QT interval \>470 ms for females and \>450 ms for males according to Fridericia's formula (QTcF) and assessed based on triplicate ECGs, approximately 1 minute apart
- LVEF \<50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan
- Myocardial infarction within 6 months
- NYHA \> class II within 6 months
- Clinically significant pericardial effusion as determined by an ECHO or MUGA scan
- Patient with history of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of first dose of tarlatamab
- Active Hepatitis B and/or Hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of cycle 1, day 1. Patients with past or resolved Hepatitis B virus (HBV) infection are eligible...
- Hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive; OR
- HBsAg positive and HBV deoxyribonucleic acid (DNA) viral load is documented to be ≤ 2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with normal...
- HBsAg positive and HBV DNA viral load is documented to be ≤ 2000 IU/mL in the absence of anti-viral therapy and during the previous 12 weeks prior to the viral load evaluation with abnormal transaminases AST/ALT \< 3...
- Patients with history or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patient is eligible if no acute symptoms of coronavirus disease 2019 (COVID-19) within 14 days prior to first...
- Patient with active or prior documented autoimmune or inflammatory disorders, including but not limited to inflammatory bowel disease [e.g. colitis or Crohn's disease], diverticulitis with the exception of...
- Patient with auto-immune alopecia
- Patient with Grave's disease, vitiligo or psoriasis not requiring systemic treatment within the last 2 years
- Patient with hypothyroidism (e.g. following Hashimoto syndrome) stable on thyroid hormone replacement
- Patient with diagnosis of human immunodeficiency virus (HIV). Patients with HIV infection on antiviral therapy and undetectable viral load are allowed with a requirement for regular monitoring for reactivation for the...
- Female patients who are pregnant or breastfeeding or intend to become pregnant during the study
- Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient...
- Patients under guardianship or deprived of his/her liberty by a judicial or administrative decision or incapable of giving his/her consent
- Prior history of severe or life-threatening events from any immune-mediated therapy
- Participation in another clinical trial (\<30 days or \< 5 half-lives, whichever is longer) evaluating an experimental drug (except non-treatment research)
The study team makes the final eligibility decision.
Where it's taking place
- Villejuif, France
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Villejuif, France. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.