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

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

Detailed Description
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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)

Official Title
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A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of Tarlatamab in Subjects With Small Cell Lung Cancer (DeLLphi-300)

Conditions
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Small Cell Lung Carcinoma

Intervention / Treatment
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* Drug: Tarlatamab
* Drug: Pembrolizumab
* Drug: CRS Mitigation Strategies


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is an open-label, ascending, multiple doses, phase 1 study evaluating tarlatamab monotherapy, in combination with anti-PD1 therapy and with additional CRS mitigation strategies in participants with SCLC. The dose exploration phases of the study will estimate the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) of tarlatamab either as monotherapy or in combination with pembrolizumab. This will be followed by dose expansion phase to confirm RP2D and to obtain further safety and efficacy data.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>Tarlatamab monotherapy | Drug: Tarlatamab<br>* Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)<br>|
| Experimental: Part C<br>Tarlatamab with Pembrolizumab | Drug: Tarlatamab<br>* Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)<br>Drug: Pembrolizumab<br>* Pembrolizumab is a potent humanized IgG4 monoclonal antibody (mAb) with high specificity of binding to the PD-1 receptor, thus inhibiting its interaction with PD-L1 and PD-L2<br>|
| Experimental: Part D<br>Tarlatamab with additional CRS mitigation strategies | Drug: Tarlatamab<br>* Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)<br>Drug: CRS Mitigation Strategies<br>* Participants will be treated with one of the CRS mitigation strategies.<br>|
| Experimental: Part E<br>Tarlatamab administration with 24-hour monitoring | Drug: Tarlatamab<br>* Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)<br>|
| Experimental: Part F<br>Tarlatamab administered in outpatient infusion centers with 8-hour monitoring Optional wearable digital device substudy (US sites only) | Drug: Tarlatamab<br>* Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)<br>|
| Experimental: Part G<br>Tarlatamab additional dosing schedule Optional wearable digital device substudy (US sites only) | Drug: Tarlatamab<br>* Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicities (DLT) for all indications |  | 6 months | 
| Number of participants with treatment-emergent adverse events (AEs) for all indications |  | 4 years | 
| Number of participants with treatment-related AEs for all indications |  | 4 years | 
| Number of participants with clinically significant changes in vital signs for all indications |  | 4 years | 
| Number of participants with significant changes in electrocardiogram (ECG) for all indications |  | 4 years | 
| Number of participants with significant changes in physical examinations for all indications |  | 4 years | 
| Number of participants with significant changes in clinical laboratory tests for all indications |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) following intravenous administration for all indications |  | 4 years | 
| Minimum observed concentration (Cmin) following intravenous administration for all indications |  | 4 years | 
| Area under the concentration-time curve (AUC) over the 2 week dosing interval for all indications |  | 4 years | 
| Accumulation following multiple dosing for all indications |  | 4 years | 
| Half-life (t1/2) following intravenous administration for all indications |  | 4 years | 
| Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Only for parts A, D, E, F, and G | 4 years | 
| Duration of Response (DOR) for all indications |  | 4 years | 
| Time to Response (TTR) |  | 4 years | 
| 9-month Progression-Free Survival (PFS) for all indications |  | 9 months | 
| 9-month Overall Survival (OS) for all indications |  | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Half-Life Extended (HLE) Bispecific T cell engager (BiTE®), Delta-like protein 3 (DLL3), Tarlatamab, Oncology, Immunology