Study of Tarlatamab + ZL-1310 +/- Anti-programmed Death Ligand 1 (Anti-PD-L1) in Small Cell Lung Cancer (SCLC) (DeLLphi-313)

Amgen

Status and phase: Enrolling; Phase 1

Conditions: Small Cell Lung Cancer

Treatments: Drug: ZL-1310; Drug: Durvalumab; Drug: Tarlatamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT07531095

20250114

2025-522888-15-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The primary objective of this trial is to evaluate the safety and tolerability of tarlatamab in combination with ZL-1310 with or without durvalumab and to determine the maximum tolerated combination dose (MTCD) and/or recommended phase 2 dose (RP2D) of ZL-1310 in combination with tarlatamab.

Enrollment: 160 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years) at the time of signing the informed consent.
• Participants with Histologically or cytologically confirmed SCLC:
• For Part 1, participants must have SCLC that has progressed or recurred following at least 1 line of platinum-based anti-cancer therapy.
• For Parts 1 and 2, participants must have progressed or recurred following at least 1 line of platinum-based therapy. No prior tarlatamab is allowed in Cohort 2-1.
• For Part 3, participants must have extensive-stage SCLC (ES-SCLC) with no prior systemic treatment other than 1 cycle of platinum-based chemotherapy.

Note: Participants with prior treatment for limited-stage SCLC (LS-SCLC) before diagnosis of ES SCLC are permitted.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• At least 1 measurable lesion as defined per RECIST v1.1 within 21-day screening period, not previously irradiated.
• Adequate organ function (hematological, coagulation, renal, hepatic, pulmonary, and cardiac function).

Exclusion criteria

• Symptomatic CNS metastases. Participants with treated brain metastases are eligible provided they meet the criteria specified in the protocol.
• History of interstitial lung disease (ILD)/pneumonitis.
• Received thoracic radiation therapy within 90 days prior to first dose of trial intervention.
• Prior therapy with any delta-like ligand 3 (DLL3)-directed therapy.
• Prior exposure to topoisomerase I inhibitors or antibody-drug conjugate (ADC) with topoisomerase I inhibitor payload.
• Receiving strong CYP3A4 or CPY2D6 inhibitors within 14 days or 5 half-lives (whichever is longer) before the first dose of trial treatment.
• Enrollment in any tarlatamab clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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160 participants in 3 patient groups

Dose Exploration (Part 1)

Experimental group

Description:

Multiple dose levels of ZL-1310 will be explored in combination with tarlatamab administered intravenously (IV).

Treatment:

Drug: Tarlatamab

Drug: ZL-1310

Dose Expansion (Part 2)

Experimental group

Description:

ZL-1310 will be administered IV at the selected maximum tolerated combination dose (MTCD) or recommended phase 2 dose (RP2D) in combination with tarlatamab administered IV.

Treatment:

Drug: Tarlatamab

Drug: ZL-1310

Triplet Combination (Part 3)

Experimental group

Description:

ZL-1310 will be administered at MTCD or RP2D in combination with tarlatamab and an anti-PD-L1 (durvalumab) each administered IV.

Treatment:

Drug: Tarlatamab

Drug: Durvalumab

Drug: ZL-1310