Clinical trial NCT05060016: A Phase 2 Study of Tarlatamab in Patients With Small Cell Lung Cancer (SCLC)
Official title: 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).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Relapsed/Refractory Small Cell Lung Cancer
Keywords: Small Cell Lung Cancer
SCLC
AMG 757
Tarlatamab
IMDELLTRA^TM
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2021-09-28
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


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 1.
* 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:

  1. 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.
  2. 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 8.
* 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 8.
* 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.

Primary outcomes:
measure: Part 1 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator
timeFrame: Up to a maximum of 24 months
measure: Part 1 and Part 3 Only: Number of Participants who Experience One or More Treatment-emergent Adverse Events
timeFrame: Up to a maximum of 24 months
measure: Part 1 Only: Serum Concentrations of Tarlatamab
timeFrame: Up to a maximum of 24 months
measure: 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)
timeFrame: Up to a maximum of 24 months
Secondary outcomes:
measure: Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)
timeFrame: Up to a maximum of 24 months
measure: Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)
timeFrame: Up to a maximum of 24 months
measure: Duration of Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)
timeFrame: Up to a maximum of 24 months
measure: Progression-free Survival (PFS) Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)
timeFrame: Up to a maximum of 24 months
measure: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator
timeFrame: Up to a maximum of 24 months
measure: Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator
timeFrame: Up to a maximum of 24 months
measure: Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator
timeFrame: Up to a maximum of 24 months
measure: Duration of Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator
timeFrame: Up to a maximum of 24 months
measure: Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator
timeFrame: Up to a maximum of 24 months
measure: Overall Survival (OS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator
timeFrame: Up to a maximum of 24 months
measure: Number of Participants who Experience One or More Treatment-emergent Adverse Events
timeFrame: Up to a maximum of 24 months
measure: Serum Concentrations of Tarlatamab
timeFrame: Up to a maximum of 24 months
measure: Number of Participants who Experience Anti-Tarlatamab Antibody Formation
timeFrame: Up to a maximum of 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Dana Farber - Harvard Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Hanover
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Comprehensive Cancer Research Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Cancer Pavillion
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Morgantown
country: United States
facility: West Virginia University Health Sciences Center
state: West Virginia
city: Krems
country: Austria
facility: Universitaetsklinikum Krems
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Gilly
country: Belgium
facility: Grand Hopital de Charleroi - Site Saint Joseph
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Marseille Cedex 20
country: France
facility: Centre Hospitalier Universitaire Nord
city: Paris Cedex 05
country: France
facility: Institut Curie
city: Pierre-Benite cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou
city: Strasbourg cedex
country: France
facility: Centre Hospitalier Universitaire de Strasbourg - Nouvel Hopital Civil
city: Toulouse cedex 9
country: France
facility: Centre Hospitalier Universitaire de Toulouse - Hopital Larrey
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Grosshansdorf
country: Germany
facility: LungenClinic Grosshansdorf GmbH
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Athens
country: Greece
facility: Henry Dunant Hospital Center
city: Athens
country: Greece
facility: Sotiria General Hospital
city: Athens
country: Greece
facility: Metropolitan Hospital
city: Heraklion - Crete
country: Greece
facility: University Hospital of Heraklion
city: Patra
country: Greece
facility: General Hospital of Patras Agios Andreas
city: Thessaloniki
country: Greece
facility: Theagenion Cancer Hospital
city: Thessaloniki
country: Greece
facility: Euromedica General Clinic of Thessaloniki
city: Thessaloniki
country: Greece
facility: Agios Loukas Clinic
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma
city: Rome
country: Italy
facility: Istituti Fisioterapici Ospitalieri Regina Elena San Gallicano
city: Varese
country: Italy
facility: Azienda Socio Sanitaria Territoriale dei Sette Laghi Ospedale di Circolo e Fondazione Macchi
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Okayama-shi
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Wakayama-shi
country: Japan
facility: Wakayama Medical University Hospital
state: Wakayama
city: Goyang-si Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung medical center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Centra Medyczne Medyceusz Sp zoo
city: Otwock
country: Poland
facility: Mazowieckie centrum leczenia
city: Lisboa
country: Portugal
facility: Hospital da Luz, SA
city: Lisboa
country: Portugal
facility: Hospital CUF Descobertas
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto EPE - Hospital de Santo Antonio
city: Porto
country: Portugal
facility: Hospital Cuf porto
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
state: Andalucía
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Cataluña
city: Hospitalet de Llobregat
country: Spain
facility: Instituto Catalan de Oncologia Hospital Duran i Reynals
state: Cataluña
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
state: Comunidad Valenciana
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Geneve 14
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: Manchester
country: United Kingdom
facility: Christie Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Bustamante Alvarez J, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L; DeLLphi-301 Investigators. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 30;389(22):2063-2075. doi: 10.1056/NEJMoa2307980. Epub 2023 Oct 20.
citation: Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Alvarez JB, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L. Plain language summary: tarlatamab for patients with previously treated small cell lung cancer. Future Oncol. 2024 Dec;20(40):3355-3364. doi: 10.1080/14796694.2024.2402152. Epub 2024 Nov 12.
citation: Hummel HD, Ahn MJ, Blackhall F, Reck M, Akamatsu H, Ramalingam SS, Borghaei H, Johnson M, Dirnberger F, Cocks K, Huang S, Mukherjee S, Paz-Ares L. Patient-Reported Outcomes for Patients with Previously Treated Small Cell Lung Cancer Receiving Tarlatamab: Results from the DeLLphi-301 Phase 2 Trial. Adv Ther. 2025 Apr;42(4):1950-1964. doi: 10.1007/s12325-025-03136-4. Epub 2025 Mar 3.