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First-Line Tarlatamab in Combination With Carboplatin, Etoposide, and PD-L1 Inhibitor in Subjects With Extensive Stage Small Cell Lung Cancer (ES-SCLC)

Phase 1
Recruiting
Conditions
Extensive Stage Small Cell Lung Cancer
Interventions
Registration Number
NCT05361395
Lead Sponsor
Amgen
Brief Summary

This is a phase 1b study to assess the safety and tolerability of tarlatamab in combination with programmed death ligand (PD-L1) inhibition with and without chemotherapy.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
340
Inclusion Criteria
  • Participant has provided informed consent prior to initiation of any study specific activities/procedures.
  • Age greater than or equal to 18 years old at the same time of signing the informed consent.
  • Histologically or cytologically confirmed Extensive Stage Small Cell Lung Cancer (ES-SCLC) and no prior systemic treatment for ES-SCLC.
  • Participants with prior treatment for limited-stage SCLC (LS-SCLC) are permitted.
  • Eastern Cooperative Oncology Group (ECOG) 0 to 1.
  • Participants with treated asymptomatic brain metastases are eligible provided they meet defined criteria.
  • Adequate organ function as defined in protocol.
Exclusion Criteria
  • History of other malignancy within the past 2 years with exceptions.
  • Major surgery within 28 days of study day 1.
  • Untreated or symptomatic brain metastases and leptomeningeal disease.
  • Participants who experienced recurrent grade 2 pneumonitis or severe or life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents.
  • History of immune-related colitis.
  • History or evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Participants 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
  • Participant has known active infection requiring parenteral antibiotic treatment. Upon completion of parenteral antibiotics and resolution of symptoms, the participant may be considered eligible for the study from an infection standpoint
  • NOTE: Simple urinary tract infections and uncomplicated bacterial pharyngitis are permitted if responding to an active treatment and after consultation with Medical Monitor. Participants requiring oral antibiotics who have been afebrile for >24 hours, have no leukocytosis, nor clinical signs of infection are eligible. Screening for chronic infectious conditions is not required.
  • History of hypophysitis or pituitary dysfunction.
  • History of solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
  • Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study. Participants with Type I diabetes, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are permitted.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part 4: Dose ExpansionAtezolizumabExpansion of Part 1, Part 2, or Part 3 with Atezolizumab
Part 5: Dose Exploration MaintenanceTarlatamabTarlatamab+Atezolizumab
Part 5: Dose Exploration MaintenanceAtezolizumabTarlatamab+Atezolizumab
Part 6: Dose Expansion MaintenanceAtezolizumabExpansion of Part 5 with Atezolizumab
Part 1: Dose Exploration Combination Regimen 1TarlatamabTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 7: Dose ExpansionTarlatamabExpansion of Part 1, 2, or 3 with Durvalumab
Part 7: Dose ExpansionDurvalumabExpansion of Part 1, 2, or 3 with Durvalumab
Part 1: Dose Exploration Combination Regimen 1CarboplatinTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 1: Dose Exploration Combination Regimen 1EtoposideTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 1: Dose Exploration Combination Regimen 1AtezolizumabTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 2: Dose Exploration Combination Regimen 2TarlatamabTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 2: Dose Exploration Combination Regimen 2CarboplatinTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 2: Dose Exploration Combination Regimen 2EtoposideTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 2: Dose Exploration Combination Regimen 2AtezolizumabTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 3: Dose Exploration Combination Regimen 3EtoposideTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 3: Dose Exploration Combination Regimen 3CarboplatinTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 3: Dose Exploration Combination Regimen 3AtezolizumabTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 4: Dose ExpansionEtoposideExpansion of Part 1, Part 2, or Part 3 with Atezolizumab
Part 4: Dose ExpansionCarboplatinExpansion of Part 1, Part 2, or Part 3 with Atezolizumab
Part 6: Dose Expansion MaintenanceTarlatamabExpansion of Part 5 with Atezolizumab
Part 7: Dose ExpansionCarboplatinExpansion of Part 1, 2, or 3 with Durvalumab
Part 7: Dose ExpansionEtoposideExpansion of Part 1, 2, or 3 with Durvalumab
Part 8: Dose Expansion MaintenanceTarlatamabExpansion of Part 5 with Durvalumab
Part 8: Dose Expansion MaintenanceDurvalumabExpansion of Part 5 with Durvalumab
Part 9: Dose Expansion MaintenanceTarlatamabExpansion with Tarlatamab+Durvalumab
Part 9: Dose Expansion MaintenanceDurvalumabExpansion with Tarlatamab+Durvalumab
Part 3: Dose Exploration Combination Regimen 3TarlatamabTarlatamab+Atezolizumab+Carboplatin+Etoposide
Part 4: Dose ExpansionTarlatamabExpansion of Part 1, Part 2, or Part 3 with Atezolizumab
Primary Outcome Measures
NameTimeMethod
Number of Participants with Clinically Significant Changes in Vital Signs24 months
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Measurements24 months
Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests24 months
Number of Participants with a Dose Limiting Toxicity (DLT)24 months
Number of Participants with Treatment-emergent Adverse Events (TEAE)24 months
Number of Participants with Treatment-related Adverse Events24 months
Secondary Outcome Measures
NameTimeMethod
6-month Progression-free Survival (PFS)24 months
Objective Response (OR)24 months

Per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Duration of Response (DOR)24 months
Disease Control Rate(DCR)24 months
Overall Survival (OS)24 months
Serum Concentration of Tarlatamab24 months

Trial Locations

Locations (44)

University of Southern California, Norris Comprehensive Cancer Center

🇺🇸

Los Angeles, California, United States

Christiana Care Health Services

🇺🇸

Newark, Delaware, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Rutgers Cancer Institute of New Jersey

🇺🇸

New Brunswick, New Jersey, United States

New York University Grossman School of Medicine and New York University Langone Hospitals

🇺🇸

New York, New York, United States

The University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Avera Cancer Institute

🇺🇸

Sioux Falls, South Dakota, United States

Swedish Cancer Institute Medical Oncology

🇺🇸

Seattle, Washington, United States

West Virginia University Health Sciences Center

🇺🇸

Morgantown, West Virginia, United States

Chris OBrien Lifehouse

🇦🇺

Camperdown, New South Wales, Australia

Universitair Ziekenhuis Antwerpen

🇧🇪

Edegem, Belgium

Algemeen Ziekenhuis Maria Middelares

🇧🇪

Gent, Belgium

Jessa Ziekenhuis - Campus Virga Jesse

🇧🇪

Hasselt, Belgium

AZ Delta Campus Rumbeke

🇧🇪

Roeselare, Belgium

Princess Margaret Cancer Centre

🇨🇦

Toronto, Ontario, Canada

CHU de Quebec Hopital de l Enfant Jesus

🇨🇦

Quebec, Canada

Rigshospitalet

🇩🇰

Kobenhavn, Denmark

Centre Leon Berard

🇫🇷

Lyon cedex 8, France

Centre Hospitalier Universitaire de Nantes, Hôpital Nord Laënnec

🇫🇷

Saint Herblain, France

Gustave Roussy

🇫🇷

Villejuif, France

Universitaetsklinikum Dresden

🇩🇪

Dresden, Germany

Universitaetsklinikum Essen

🇩🇪

Essen, Germany

Universitaetsklinikum Freiburg

🇩🇪

Freiburg, Germany

Rambam Medical Center

🇮🇱

Haifa, Israel

Hadassah Ein-Kerem Medical Center

🇮🇱

Jerusalem, Israel

Rabin Medical Center

🇮🇱

Petah Tikva, Israel

Sheba Medical Center

🇮🇱

Ramat Gan, Israel

Azienda Ospedaliera Universitaria Renato Dulbecco

🇮🇹

Catanzaro, Italy

Fondazione IRCCS San Gerardo dei Tintori

🇮🇹

Monza (MB), Italy

Istituto Nazionale Tumori Regina Elena

🇮🇹

Rome, Italy

National Cancer Center Hospital East

🇯🇵

Kashiwa-shi, Chiba, Japan

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

🇯🇵

Koto-ku, Tokyo, Japan

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Universitair Medisch Centrum Groningen

🇳🇱

Groningen, Netherlands

Institut Catala d Oncologia Badalona Hospital Universitari Germans Trias i Pujol

🇪🇸

Badalona, Cataluña, Spain

Hospital Universitari Vall d Hebron

🇪🇸

Barcelona, Cataluña, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Universitaetsspital Basel

🇨🇭

Basel, Switzerland

Inselspital Bern

🇨🇭

Bern, Switzerland

National Cheng Kung University Hospital

🇨🇳

Tainan, Taiwan

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

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