A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Tarlatamab in Combination With AB248 in Participants With Extensive Stage Small Cell Lung Cancer (DeLLphi-311)
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Amgen
- Enrollment
- 380
- Locations
- 28
- Primary Endpoint
- Dose Exploration: Number of Participants with Dose-limiting Toxicities (DLTs)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Dose Expansion
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.
Intervention: Tarlatamab (Drug)
Dose Exploration
Multiple dose levels of AB248 will be explored in combination with tarlatamab administered via intravenous (IV) infusion.
Intervention: Tarlatamab (Drug)
Dose Expansion
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.
Intervention: AB248 (Drug)
Dose Exploration
Multiple dose levels of AB248 will be explored in combination with tarlatamab administered via intravenous (IV) infusion.
Intervention: AB248 (Drug)
Outcomes
Primary Outcomes
Dose Exploration: Number of Participants with Dose-limiting Toxicities (DLTs)
Time Frame: Up to 35 days
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time Frame: Up to 2.5 years
Clinically significant changes in vital signs and clinical laboratory tests will be reported as adverse events.
Secondary Outcomes
- Duration of Response (DOR) per RECIST 1.1(Up to 2.5 years)
- Maximum Serum Concentration (Cmax) of Tarlatamab(Up to approximately 21 weeks)
- Minimum Serum Concentration (Cmin) of Tarlatamab(Up to approximately 21 weeks)
- 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)
- 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)
- Number of Participants with Anti-AB248 Antibody Formation(Up to 2.5 years)