NCT05060016
Active, not recruiting
Phase 2
A Phase 2 Study Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of Tarlatamab in Subjects With Relapsed/Refractory Small Cell Lung Cancer After Two or More Prior Lines of Treatment (DeLLphi-301).
Overview
- Phase
- Phase 2
- Intervention
- Tarlatamab
- Conditions
- Relapsed/Refractory Small Cell Lung Cancer
- Sponsor
- Amgen
- Enrollment
- 222
- Locations
- 80
- Primary Endpoint
- Part 1 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator
- Status
- Active, not recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
The main aim of this study is to:
- evaluate safety and efficacy (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1] by investigator) of 2 dose levels of tarlatamab for Part 1 only
- evaluate anti-tumor activity of tarlatamab as determined by objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR) for Part 1 and 2
- evaluate safety of reduced mandatory monitoring period in Cycle 1 at selected dose of tarlatamab for Part 3
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures.
- •Male and female participants ≥ 18 years of age (or legal adult age within country) at the time of signing the informed consent.
- •Histologically or cytologically confirmed relapsed/refractory SCLC
- •Participants who progressed or recurred following 1 platinum-based regimen and at least 1 other prior line of therapy.
- •Participants willing to provide archived tumor tissue samples or willing to undergo pretreatment tumor biopsy.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0
- •Minimum life expectancy of 12 weeks.
- •Measurable lesions as defined per RECIST 1.1 within 21 days prior to the first dose of tarlatamab.
- •Participants with treated brain metastases are eligible provided they meet defined criteria.
Exclusion Criteria
- •Disease Related
- •Untreated or symptomatic brain metastases and leptomeningeal disease.
- •Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- •Participants who experienced recurrent pneumonitis (grade 2 or higher) or severe, life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents.
- •Unresolved toxicity from prior anti-tumor therapy, defined as per protocol.
- •Other Medical Conditions
- •History of other malignancy within the past 2 years, with exceptions
- •Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association \> class II) within 12 months of first dose of tarlatamab.
- •History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of first dose of tarlatamab.
- •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 tarlatamab.
Arms & Interventions
Part 1: Tarlatamab Low Dose
Participants will receive the low dose of Tarlatamab.
Intervention: Tarlatamab
Part 1: Tarlatamab High Dose
Participants will receive the high dose of Tarlatamab.
Intervention: Tarlatamab
Part 2: Dose Expansion
Participants will receive the selected target dose of Tarlatamab based on findings in Part 1.
Intervention: Tarlatamab
Part 3: Modified Monitoring Substudy
Participants will receive the selected target dose of Tarlatamab based on findings in Part 1 with reduced Cycle 1 monitoring requirements.
Intervention: Tarlatamab
Outcomes
Primary Outcomes
Part 1 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator
Time Frame: Up to a maximum of 61 months
Part 1 and Part 3 Only: Number of Participants who Experience One or More Treatment-emergent Adverse Events
Time Frame: Up to a maximum of 61 months
Part 1 Only: Serum Concentrations of Tarlatamab
Time Frame: Up to a maximum of 24 months
Part 1 and Part 2 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)
Time Frame: Up to a maximum of 61 months
Secondary Outcomes
- Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)(Up to a maximum of 73 months)
- Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)(Up to a maximum of 73 months)
- Duration of Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)(Up to a maximum of 73 months)
- Progression-free Survival (PFS) Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)(Up to a maximum of 73 months)
- Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator(Up to a maximum of 73 months)
- Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator(Up to a maximum of 73 months)
- Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator(Up to a maximum of 73 months)
- Duration of Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator(Up to a maximum of 73 months)
- Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator(Up to a maximum of 73 months)
- Overall Survival (OS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator(Up to a maximum of 73 months)
- Number of Participants who Experience One or More Treatment-emergent Adverse Events(Up to a maximum of 73 months)
- Serum Concentrations of Tarlatamab(Up to a maximum of 24 months)
- Number of Participants who Experience Anti-Tarlatamab Antibody Formation(Up to a maximum of 73 months)
Study Sites (80)
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Related News
Tarlatamab Approved in the UK for Previously Treated Extensive-Stage Small Cell Lung Cancer- The UK's MHRA has granted conditional marketing authorization to tarlatamab (Imdelltra) for extensive-stage small cell lung cancer (ES-SCLC) after two or more prior lines of therapy.
- The approval was based on the DeLLphi-301 phase 2 trial, which showed a 41% objective response rate in patients treated with tarlatamab 10 mg every 2 weeks.
- Tarlatamab demonstrated a median duration of response of 9.7 months and a median overall survival of 15.2 months in previously treated ES-SCLC patients.
- Common adverse events included cytokine release syndrome, pyrexia, and dysgeusia, but the drug offers a new treatment option for a cancer with poor outcomes.MHRA Approves Amgen's Imdylltra (Tarlatamab) for Advanced Small Cell Lung Cancer- The UK's MHRA has granted conditional marketing authorization to Amgen's Imdylltra (tarlatamab) for extensive-stage small cell lung cancer (ES-SCLC).
- The approval is for adult patients who have progressed after at least two prior lines of therapy, including platinum-based chemotherapy.
- Tarlatamab demonstrated a 41% objective response rate and a 9.7-month median duration of response in the Phase 2 DeLLphi-301 trial.
- Imdylltra, a bispecific T-cell engager targeting DLL3, offers a new treatment option for ES-SCLC patients with limited alternatives.FDA Approves Obecabtagene Autoleucel for R/R B-ALL; Advances in SCLC and Multiple Myeloma Highlighted- The FDA approved obecabtagene autoleucel (obe-cel) for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) based on the phase 1b/2 FELIX trial data.
- Tarlatamab and lurbinectedin are shifting the treatment landscape for small cell lung cancer (SCLC) due to their improved toxicity profiles.
- LBL-034, a bispecific antibody targeting GPRC5D and CD3, received orphan drug designation for multiple myeloma treatment and is being evaluated in a phase 1/2 trial.FDA Grants Accelerated Approval to Tarlatamab for Previously Treated Extensive-Stage Small Cell Lung Cancer- Tarlatamab (Imdelltra) receives accelerated FDA approval for extensive-stage small cell lung cancer (SCLC) post-platinum-based chemotherapy.
- The approval was based on the DeLLphi-301 study, which demonstrated a 40% objective response rate among evaluable patients.
- The median duration of response in the study was 9.7 months, with a significant proportion of responses lasting over 6 months.
- Common adverse events included cytokine-release syndrome, fatigue, and pyrexia, necessitating careful monitoring and management.SCLC Treatment Landscape Evolves with Tarlatamab Approval and Promising Trial Results- The FDA approved tarlatamab in May 2024 for SCLC that has progressed after platinum-based chemotherapy, marking a new treatment option in the second-line setting.
- The ADRIATIC trial demonstrated that consolidation durvalumab significantly improved PFS and OS in patients with limited-stage SCLC after chemoradiation.
- The IMforte trial showed that lurbinectedin combined with atezolizumab led to significant benefits in overall survival and progression-free survival as a maintenance therapy.
- Research is exploring novel agents like B7-H3 targeted antibody-drug conjugates and DLL3-targeted bispecific T-cell engagers to further improve SCLC treatment outcomes.