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) ((DeLLphi-310))

Amgen

Status and phase: Enrolling; Phase 1

Conditions: Small Cell Lung Cancer

Treatments: Drug: Tarlatamab; Drug: Durvalumab; Drug: YL201; Drug: Atezolizumab

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT06898957

20240124 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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200 participants in 3 patient groups

Dose Exploration (Part 1)

Experimental group

Description:

Multiple dose levels of YL201 will be explored in combination with tarlatamab administered intravenously (IV) at a fixed dose using one-step dosing.

Treatment:

Drug: YL201

Drug: Tarlatamab

Dose Expansion (Part 2)

Experimental group

Description:

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.

Treatment:

Drug: YL201

Drug: Tarlatamab

Triplet Combination (Part 3)

Experimental group

Description:

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.

Treatment:

Drug: Atezolizumab

Drug: YL201

Drug: Durvalumab

Drug: Tarlatamab