A Study of Tarlatamab in Combination With AB248 in Participants With Extensive Stage Small Cell Lung Cancer (DeLLphi-311)
Phase 1
Not yet recruiting
- Conditions
- Extensive Stage Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT07037758
- Lead Sponsor
- Amgen
- Brief Summary
The primary objective for dose exploration and dose expansion is to evaluate the safety and tolerability of tarlatamab in combination with AB248.
The primary objective for dose exploration only is to determine the recommended dose for expansion and/or maximum tolerated combination dose (MTCD) of AB248 in combination with tarlatamab.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 380
Inclusion Criteria
- Participant has provided informed consent before initiation of any study-specific activities/procedures.
- Participants ≥ 18 years (or ≥ legal age within the country if it is older than 18 years) at the time of signing the informed consent.
- Participants with histologically or cytologically confirmed ES-SCLC that has progressed or recurred following at least 1 line of anti-cancer therapy for ES-SCLC.
- Participants must have at least 1 measurable lesion as defined by RECIST 1.1 within 21-day screening period, not previously irradiated.
- Participants must have adequate organ function (hematological, coagulation, cardiac, pulmonary, kidney, and liver).
- Participants must submit a fresh tumor biopsy at screening unless a new biopsy cannot be performed safely or is infeasible. Participants who cannot provide fresh tissue may provide archival tissue that was collected after last anticancer therapy.
Exclusion Criteria
- Symptomatic central nervous system (CNS) metastases.
- Participants with brain metastases may be eligible if criteria defined in the protocol are met.
- Prior therapy with any delta-like ligand 3 (DLL3)-directed therapy (including tarlatamab).
- Prior interleukin (IL)-2, IL-7 or IL-15 targeted therapy.
- Baseline (at rest) requirement of supplemental oxygen.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Exploration Tarlatamab Multiple dose levels of AB248 will be explored in combination with tarlatamab administered via intravenous (IV) infusion. Dose Exploration AB248 Multiple dose levels of AB248 will be explored in combination with tarlatamab administered via intravenous (IV) infusion. Dose Expansion Tarlatamab The dose expansion part will test tarlatamab in combination with the MTCD/recommended dose for expansion of AB248 identified in the dose exploration part. An optional cohort may be opened based on emerging data to study tarlatamab in combination with AB248 at a lower dose than the MTCD/recommended dose for expansion or with an alternative dose regimen at a AB248 dose lower than or equal to MTCD/recommended dose for expansion. Dose Expansion AB248 The dose expansion part will test tarlatamab in combination with the MTCD/recommended dose for expansion of AB248 identified in the dose exploration part. An optional cohort may be opened based on emerging data to study tarlatamab in combination with AB248 at a lower dose than the MTCD/recommended dose for expansion or with an alternative dose regimen at a AB248 dose lower than or equal to MTCD/recommended dose for expansion.
- Primary Outcome Measures
Name Time Method Dose Exploration: Number of Participants with Dose-limiting Toxicities (DLTs) Up to 35 days Number of Participants with Treatment-emergent Adverse Events (TEAEs) Up to 2.5 years Clinically significant changes in vital signs and clinical laboratory tests will be reported as adverse events.
- Secondary Outcome Measures
Name Time Method Time to Response (TTR) per RECIST 1.1 Up to 2.5 years Disease Control (DC) per RECIST 1.1 Up to 2.5 years Progression-free Survival (PFS) per RECIST 1.1 Up to 2.5 years Time to Progression (TTP) per RECIST 1.1 Up to 2.5 years Time to Subsequent Therapy Up to 2.5 years Overall Survival (OS) Up to 2.5 years Minimum Serum Concentration (Cmin) of Tarlatamab Up to approximately 21 weeks Area Under the Concentration-time Curve (AUC) of Tarlatamab Up to approximately 21 weeks Half-life (t1/2) of Tarlatamab Up to approximately 21 weeks Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Up to 2.5 years Duration of Response (DOR) per RECIST 1.1 Up to 2.5 years Maximum Serum Concentration (Cmax) of Tarlatamab Up to approximately 21 weeks Number of Participants with Anti-AB248 Antibody Formation Up to 2.5 years