NCT05060016Active, not recruitingPhase 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).
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Amgen
- Enrollment
- 222
- Locations
- 146
- Primary Endpoint
- Part 1 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator
Study 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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
- •Presence of any indwelling line or drain.
- •History of hypophysitis or pituitary dysfunction.
- •Exclusion of hepatitis infection based on the results and/or criteria per protocol.
- •Major surgery within 28 days of first dose of tarlatamab.
- •History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Subject is eligible if no acute symptoms of coronavirus disease 2019 (COVID-19) within 14 days prior to first dose of tarlatamab (counted from day of positive test for asymptomatic subjects).
- •Prior/Concomitant Therapy
- •Participant received prior therapy with tarlatamab.
- •Prior anti-cancer therapy within 28 days prior to first dose of tarlatamab.
- •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.
- •The following vaccines (live and live-attenuated vaccines) are excluded during the following study periods:
- •Screening and during study treatment: Live and live-attenuated vaccines are prohibited within 28 days prior to the first dose of tarlatamab and for the duration of the study. Live viral non-replicating vaccine (e.g. Jynneos) for Monkeypox infection is allowed during the study (except during cycle 1) in accordance with local standard of care and institutional guidelines.
- •End of study treatment: Live and live-attenuated vaccines can be used when at least 42 days (5X half-life of tarlatamab) have passed after the last dose of tarlatamab.
- •Other Exclusions
- •Female participants of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 60 days after the last dose of tarlatamab.
- •Female participants who are breastfeeding or who plan to breastfeed while on study through 60 days after the last dose of tarlatamab.
- •Female participants planning to become pregnant while on study through 60 days after the last dose of tarlatamab.
- •Female participants of childbearing potential with a positive pregnancy test assessed at screening and/or day 1 by a highly sensitive urine or serum pregnancy test.
- •Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 60 days after the last dose of tarlatamab.
- •Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 60 days after the last dose of tarlatamab.
- •Male participants unwilling to abstain from donating sperm during treatment and for an additional 60 days after the last dose of tarlatamab.
- •Participant has known sensitivity to any of the products or components to be administered during dosing.
- •Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures.
- •History or evidence of any other clinically significant disorder, condition or disease determined by the investigator or Amgen physician.
- •Specific Exclusions to Part 3
- •Participants unable to remain within one hour of study site for 48 hours after infusion of tarlatamab on Cycle 1 Day 1 and Cycle 1 Day
- •Participants unable to remain within one hour of any hospital for 72 hours after infusion of tarlatamab on Cycle 1 Day 1 and Cycle 1 Day
- •Unable to identify home companion who will cohabitate with participant for 72 hours after infusion of tarlatamab on Cycle 1 Day 1 and Cycle 1 Day 8.
Arms & Interventions
Part 1: Tarlatamab Low Dose
Experimental
Participants will receive the low dose of Tarlatamab.
Intervention: Tarlatamab (Drug)
Part 1: Tarlatamab High Dose
Experimental
Participants will receive the high dose of Tarlatamab.
Intervention: Tarlatamab (Drug)
Part 2: Dose Expansion
Experimental
Participants will receive the selected target dose of Tarlatamab based on findings in Part 1.
Intervention: Tarlatamab (Drug)
Part 3: Modified Monitoring Substudy
Experimental
Participants will receive the selected target dose of Tarlatamab based on findings in Part 1 with reduced Cycle 1 monitoring requirements.
Intervention: Tarlatamab (Drug)
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
Part 1 Only: Serum Concentrations of Tarlatamab
Time Frame: Up to a maximum of 24 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)
- Serum Concentrations of Tarlatamab(Up to a maximum of 24 months)
Investigators
Study Sites (146)
Loading locations...
Similar Trials
Completed
Phase 2
A Study of 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic LeukemiaChronic Myelomonocytic LeukemiaNCT01350947University of Utah11
Completed
Phase 2
Efficacy and Safety Study of Idelalisib in Participants With Indolent B-Cell Non-Hodgkin LymphomasSmall Lymphocytic LymphomaLymphoplasmacytic LymphomaMarginal Zone LymphomaFollicular LymphomaNCT01282424Gilead Sciences125
Completed
Phase 1
AMG 757 and AMG 404 in Subjects With Small Cell Lung Cancer (SCLC)Small Cell Lung CancerNCT04885998Amgen23
Recruiting
Phase 2
A Study of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate ThrombocytopeniaModerate ThrombocytopeniaMyelofibrosisNCT05980806Karyopharm Therapeutics Inc58
Active, not recruiting
Phase 1
A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial CancerUrothelial CarcinomaNCT03473743Janssen Research & Development, LLC125
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.last yearMHRA 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.last yearFDA 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.last yearFDA 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.last yearSCLC 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.last year