Clinical trial NCT04885998: AMG 757 and AMG 404 in Subjects With Small Cell Lung Cancer (SCLC)
Official title: A Phase 1b Study Evaluating the Safety and Efficacy of AMG 757 in Combination With AMG 404 in Subjects With Small Cell Lung Cancer (SCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Small Cell Lung Cancer
Keywords: Small Cell Lung Cancer
SCLC
Lung Cancer
AMG 757
AMG 404
Tarlatamab
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2021-05-13
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety, tolerability, and recommended phase 2 target dose of tarlatamab in combination with AMG 404.


Eligibility criteria: Inclusion Criteria:

* Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures
* Age greater than or equal to 18 years old at the same time of signing the informed consent
* Participants with histologically or cytologically confirmed Small Cell Lung Cancer (SCLC) who progressed or recurred following at least 1 platinum-based regimen
* Eastern Cooperative Oncology Group (ECOG) 0 to 1
* Participants with treated brain metastases are eligible provided they meet defined criteria
* Adequate organ function as defined in protocol

Exclusion Criteria:

* History of other malignancy within the past 2 years with exceptions
* Major surgery within 28 days of first dose of tarlatamab
* Untreated or symptomatic brain metastases and leptomeningeal disease
* Prior anti-cancer therapy, including anti-PD1 or anti-PDL1 antibody therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and the first planned dose of tarlatamab

Exceptions:

* Participants who received prior chemotherapy must have completed at least 14 days before the first dose of tarlatamab and all treatment-related toxicity resolved to grade ≤ 1.
* Participants who received prior palliative radiotherapy must have completed at least 7 days before the first dose of tarlatamab

  * Participants who received prior tarlatamab therapy or prior delta-like ligand 3 (DLL3) x cluster of differentiation 3 (CD3) bispecific therapy are not eligible
  * Participants who experienced recurrent grade 2 pneumonitis or severe or life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents
  * History of any immune-related colitis. Infectious colitis is allowed if evidence of adequate treatment and clinical recovery exists and at least 3 months interval observed since diagnosis of colitis
  * Participants with evidence of interstitial lung disease or active, non-infectious pneumonitis
  * 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
  * History of solid organ transplantation
  * History of hypophysitis or pituitary dysfunction
  * Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study. Participants with Type I diabetes, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are permitted

Primary outcomes:
measure: Number of Participants Who Experienced Dose-limiting Toxicity (DLT)
timeFrame: First dose of tarlatamb or AMG 404 up to 28 days
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: First dose of IP up to 47 days after the last dose of IP (safety follow-up 1 [SFU1]; median duration was 3.0 months); and from the end of SFU1 up to 145 days after the last dose of IP (EP; median duration was 1.7 months)
Secondary outcomes:
measure: Objective Response Rate Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Cycle 1 day 1 up to 24 months
measure: Kaplan-Meier Estimate of Duration of Response Per Modified RECIST v1.1
timeFrame: Cycle day 1 up to 24 months
measure: Disease Control Rate Per Modified RECIST v1.1
timeFrame: Cycle day 1 up to 24 months
measure: Kaplan-Meier Estimate of Progression-free Survival Per Modified RECIST v1.1
timeFrame: Cycle day 1 up to 24 months
measure: Kaplan-Meier Estimate of Overall Survival
timeFrame: Cycle day 1 up to 24 months
measure: Maximum Observed Concentration (Cmax) of Tarlatamab in Combination With AMG 404
timeFrame: Cycles 1 and 2 day 1 pre-infusion; Cycles 3 and 4 day 1 pre- and post-infusion; and for Cycle 5 onwards, day 1 of each cycle at pre-infusion
measure: Minimum Observed Concentration (Cmin) of Tarlatamab in Combination With AMG 404
timeFrame: Cycles 1 and 2 day 1 pre-infusion; Cycles 3 and 4 day 1 pre- and post-infusion; and for Cycle 5 onwards, day 1 of each cycle at pre-infusion
measure: Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of Tarlatamab in Combination With AMG 404
timeFrame: Cycles 1 and 2 day 1 pre-infusion; Cycles 3 and 4 day 1 pre- and post-infusion; and for Cycle 5 onwards, day 1 of each cycle at pre-infusion
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University, Robert H Lurie Comprehensive Cancer Center
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Comprehensive Cancer Research Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck
city: Wien
country: Austria
facility: Universitaetsklinikum Allgemeines Krankenhaus Wien
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: