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

Amgen

Status and phase: Active, not recruiting; Phase 1

Conditions: Extensive Stage Small Cell Lung Cancer

Treatments: Drug: Tarlatamab; Drug: Etoposide; Drug: Carboplatin; Drug: Atezolizumab; Drug: Durvalumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05361395

2024-511021-58 (EudraCT Number)

20200469

Details and patient eligibility

About

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.

Enrollment: 184 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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184 participants in 9 patient groups

Part 1: Dose Exploration Combination Regimen 1

Experimental group

Description:

Tarlatamab+Atezolizumab+Carboplatin+Etoposide

Treatment:

Drug: Atezolizumab

Drug: Carboplatin

Drug: Etoposide

Drug: Tarlatamab

Part 2: Dose Exploration Combination Regimen 2

Experimental group

Description:

Tarlatamab+Atezolizumab+Carboplatin+Etoposide

Treatment:

Drug: Atezolizumab

Drug: Carboplatin

Drug: Etoposide

Drug: Tarlatamab

Part 3: Dose Exploration Combination Regimen 3

Experimental group

Description:

Tarlatamab+Atezolizumab+Carboplatin+Etoposide

Treatment:

Drug: Atezolizumab

Drug: Carboplatin

Drug: Etoposide

Drug: Tarlatamab

Part 4: Dose Expansion

Experimental group

Description:

Expansion of Part 1, Part 2, or Part 3 with Atezolizumab

Treatment:

Drug: Atezolizumab

Drug: Carboplatin

Drug: Etoposide

Drug: Tarlatamab

Part 5: Dose Exploration Maintenance

Experimental group

Description:

Tarlatamab+Atezolizumab

Treatment:

Drug: Atezolizumab

Drug: Tarlatamab

Part 6: Dose Expansion Maintenance

Experimental group

Description:

Expansion of Part 5 with Atezolizumab

Treatment:

Drug: Atezolizumab

Drug: Tarlatamab

Part 7: Dose Expansion

Experimental group

Description:

Expansion of Part 1, 2, or 3 with Durvalumab

Treatment:

Drug: Durvalumab

Drug: Carboplatin

Drug: Etoposide

Drug: Tarlatamab

Part 8: Dose Expansion Maintenance

Experimental group

Description:

Expansion of Part 5 with Durvalumab

Treatment:

Drug: Durvalumab

Drug: Tarlatamab

Part 9: Dose Expansion Maintenance

Experimental group

Description:

Expansion with Tarlatamab+Durvalumab

Treatment:

Drug: Durvalumab

Drug: Tarlatamab