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)

Phase 1

Recruiting

• Conditions: Small Cell Lung Cancer
• Interventions: Drug: YL201; Drug: Tarlatamab; Drug: Atezolizumab; Drug: Durvalumab

• Registration Number: NCT06898957
• Lead Sponsor: Amgen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-21
• Study First Submitted QC: 2025-03-21
• Study First Posted: 2025-03-27
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-11
• Last Update Posted: 2025-05-14
• Study Start: 2025-05-30
• Primary Completion: 2031-04-13
• Study Completion: 2031-04-13

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Exploration (Part 1)	YL201	Multiple dose levels of YL201 will be explored in combination with tarlatamab administered intravenously (IV) at a fixed dose using one-step dosing.
Dose Exploration (Part 1)	Tarlatamab	Multiple dose levels of YL201 will be explored in combination with tarlatamab administered intravenously (IV) at a fixed dose using one-step dosing.
Dose Expansion (Part 2)	YL201	YL201 will be administered at the selected maximum tolerated combination dose (MTCD) or recommended phase 2 dose (RP2D) in combination with tarlatamab administered IV at a fixed dose.
Dose Expansion (Part 2)	Tarlatamab	YL201 will be administered at the selected maximum tolerated combination dose (MTCD) or recommended phase 2 dose (RP2D) in combination with tarlatamab administered IV at a fixed dose.
Triplet Combination (Part 3)	YL201	YL201 will be administered at MTCD or RP2D in combination with tarlatamab and an anti-PD-L1 (atezolizumab or durvalumab) administered IV at a fixed dose.
Triplet Combination (Part 3)	Tarlatamab	YL201 will be administered at MTCD or RP2D in combination with tarlatamab and an anti-PD-L1 (atezolizumab or durvalumab) administered IV at a fixed dose.
Triplet Combination (Part 3)	Atezolizumab	YL201 will be administered at MTCD or RP2D in combination with tarlatamab and an anti-PD-L1 (atezolizumab or durvalumab) administered IV at a fixed dose.
Triplet Combination (Part 3)	Durvalumab	YL201 will be administered at MTCD or RP2D in combination with tarlatamab and an anti-PD-L1 (atezolizumab or durvalumab) administered IV at a fixed dose.

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Dose-limiting toxicities (DLTs)	Up to Day 21
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)	Up to 3.5 Years

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Up to 3.5 Years
Time to Response (TTR) per RECIST 1.1	Up to 3.5 Years
Progression-free Survival (PFS) per RECIST 1.1	Up to 3.5 Years
Overall Survival (OS)	Up to 3.5 Years
Maximum Serum Concentration (Cmax) of Tarlatamab	Up to Week 36
Minimum Serum Concentration (Cmin) of Tarlatamab	Up to Week 36
Disease Control Rate (DCR) per RECIST 1.1	Up to 3.5 Years
Duration of Response (DOR) per RECIST 1.1	Up to 3.5 Years
Time to Progression (TTP) per RECIST 1.1	Up to 3.5 Years
Time to Subsequent Therapy	Up to 3.5 Years
Area Under the Concentration-time Curve (AUC) Over the Dosing Interval for Tarlatamab	Up to Week 36
Half-life (t1/2) of Tarlatamab	Up to Week 36

Trial Locations

Locations (2)

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Shandong Cancer Hospital; 🇨🇳 Jinan, Shandong, China