Clinical trial NCT06898957: Study of Tarlatamab in Combination With YL201 With or Without Anti-programmed Death Ligand 1 (PD-L1) in Participants With Extensive Stage (ES) Small Cell Lung Cancer (SCLC)
Official title: A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Tarlatamab in Combination With YL201 With or Without Anti-PD-L1 in Subjects With Extensive Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Small Cell Lung Cancer
Keywords: Small cell lung cancer
SCLC
Tarlatamab
YL201
Anti-PD-L1
Atezolizumab
Durvalumab
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: MediLink
First posted: 2025-03-27
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and tolerability of tarlatamab in combination with YL201 with or without anti-PD-L1.


Eligibility criteria: Inclusion Criteria:

* Participants ≥ 18 years of age (or legal adult age within country) at time of signing informed consent.
* Participants with histologically or cytologically confirmed ES-SCLC.
* For Parts 1 and 2, participant must have ES-SCLC that has progressed or recurred following at least 1 line of platinum-based anti-cancer therapy.
* For Part 3, participants must have ES-SCLC and no prior systemic treatment for ES SCLC other than 1 cycle of platinum-based chemotherapy, etoposide, and PD-(L)1 inhibitor in the first-line setting.
* At least 1 measurable lesion as defined by RECIST 1.1.
* Participants must have adequate organ function (cardiac, pulmonary, kidney, bone marrow, and liver).

Exclusion Criteria:

* Prior delta-like ligand 3 (DLL3) or B7 homolog 3 (B7-H3) targeted therapy.
* Prior exposure to topoisomerase I inhibitors or antibody-drug conjugate (ADC) with topoisomerase I inhibitor payload.
* Symptomatic central nervous system (CNS) metastases. Note: Participants with asymptomatic brain metastases are eligible as defined in the protocol.
* History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
* Baseline requirement of supplemental oxygen.

Primary outcomes:
measure: Number of Participants Experiencing Dose-limiting toxicities (DLTs)
timeFrame: Up to Day 21
measure: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 3.5 Years
Secondary outcomes:
measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Up to 3.5 Years
measure: Duration of Response (DOR) per RECIST 1.1
timeFrame: Up to 3.5 Years
measure: Time to Response (TTR) per RECIST 1.1
timeFrame: Up to 3.5 Years
measure: Disease Control Rate (DCR) per RECIST 1.1
timeFrame: Up to 3.5 Years
measure: Progression-free Survival (PFS) per RECIST 1.1
timeFrame: Up to 3.5 Years
measure: Time to Progression (TTP) per RECIST 1.1
timeFrame: Up to 3.5 Years
measure: Time to Subsequent Therapy
timeFrame: Up to 3.5 Years
measure: Overall Survival (OS)
timeFrame: Up to 3.5 Years
measure: Maximum Serum Concentration (Cmax) of Tarlatamab
timeFrame: Up to Week 36
measure: Minimum Serum Concentration (Cmin) of Tarlatamab
timeFrame: Up to Week 36
measure: Area Under the Concentration-time Curve (AUC) Over the Dosing Interval for Tarlatamab
timeFrame: Up to Week 36
measure: Half-life (t1/2) of Tarlatamab
timeFrame: Up to Week 36
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: