Study Evaluating Safety, Tolerability and Pharmacokinetics (PK) of Tarlatamab in Adults With Small Cell Lung Cancer (SCLC)

Amgen

Status and phase: Active, not recruiting; Phase 1

Conditions: Small Cell Lung Carcinoma

Treatments: Drug: CRS Mitigation Strategies; Drug: Tarlatamab; Drug: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03319940

20160323

Details and patient eligibility

About

A study to assess the safety, tolerability, and PK of tarlatamab in participants with SCLC

Full description

This is an open-label, ascending, multiple doses, phase 1 study evaluating tarlatamab monotherapy, in combination with anti-PD1 therapy and with additional cytokine release syndrome (CRS) mitigation strategies. Tarlatamab will be administered as a short term intravenous (IV) infusion in participants with SCLC. Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)

Enrollment: 269 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 time of signing the informed consent
• Histologically or cytologically confirmed SCLC. For parts A, C, D, E, F, and G: relapsed/refractory small cell lung cancer (R/R SCLC) who progressed or recurred following platinum-based regimen
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Participants with treated 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 prior to first dose of tarlatamab with exceptions
• Major surgery within 28 days of first dose tarlatamab
• Untreated (includes new lesions or progression in previously treated lesions) or symptomatic brain metastases and leptomeningeal disease (regardless of symptomatic or not).
• Prior anti-cancer therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and first dose of tarlatamab with the following exceptions: participants who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to Grade less than or equal to 1; and prior palliative radiotherapy must have been completed at least 7 days before the first dose of tarlatamab
• Participants who experienced severe, life-threatening or recurrent (Grade 2 or higher) immune-mediated AEs or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immune-oncology agents
• Has 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 tarlatamab
• Part C only: history of solid organ transplantation or active autoimmune disease that has required systemic treatment within the past 2 years
• Participant 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 investigational product administration

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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269 participants in 6 patient groups

Part A

Experimental group

Description:

Tarlatamab monotherapy

Treatment:

Drug: Tarlatamab

Part C

Experimental group

Description:

Tarlatamab with Pembrolizumab

Treatment:

Drug: Pembrolizumab

Drug: Tarlatamab

Part D

Experimental group

Description:

Tarlatamab with additional CRS mitigation strategies

Treatment:

Drug: Tarlatamab

Drug: CRS Mitigation Strategies

Part E

Experimental group

Description:

Tarlatamab administration with 24-hour monitoring

Treatment:

Drug: Tarlatamab

Part F

Experimental group

Description:

Tarlatamab administered in outpatient infusion centers with 8-hour monitoring Optional wearable digital device substudy (US sites only)

Treatment:

Drug: Tarlatamab

Part G

Experimental group

Description:

Tarlatamab additional dosing schedule Optional wearable digital device substudy (US sites only)

Treatment:

Drug: Tarlatamab