Tarlatamab plus ZL-1310, with or without durvalumab, for small cell lung cancer

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Tarlatamab in Combination With ZL-1310 With or Without Anti-PD-L1 in Participants With Small Cell Lung Cancer

This trial will test whether combining tarlatamab with ZL-1310, with or without the PD-L1 drug durvalumab, is safe and tolerable for adults with small cell lung cancer who have received platinum chemotherapy or are newly diagnosed extensive-stage after one cycle of chemo.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Amgen (Industry-sponsored)
• Drugs / interventions: tarlatamab, chemotherapy, radiation, durvalumab
• Locations: 3 sites (New York, New York and 2 other locations)
• Trial ID: NCT07531095 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, dose-escalation trial that gives tarlatamab together with ZL-1310, and in some cohorts adds the anti–PD-L1 antibody durvalumab, to find the maximum tolerated combination dose and a recommended Phase 2 dose. Participants are enrolled in defined parts/cohorts based on prior therapies, with some cohorts limited to patients who have progressed after at least one line of platinum-based therapy and a part enrolling extensive-stage patients with minimal prior systemic treatment. Key eligibility includes histologically confirmed small cell lung cancer, ECOG 0–1, at least one measurable lesion per RECIST v1.1, and adequate organ function. Safety, tolerability, and dose-limiting toxicities are the primary focus, with imaging and clinical follow-up to monitor responses and adverse events.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed small cell lung cancer, ECOG performance status 0–1, at least one measurable lesion, and adequate organ function who meet the protocol-defined prior-therapy requirements for the assigned part are the intended participants.

Not a fit: Patients with poor performance status (ECOG ≥2), inadequate organ function, uncontrolled brain metastases, or those who received prior tarlatamab where excluded by cohort rules are unlikely to benefit from joining this Phase 1 dose-escalation study.

Why it matters

Potential benefit: If successful, the combination could offer a new treatment option that improves outcomes for some patients with small cell lung cancer.

How similar studies have performed: Early clinical work with tarlatamab has shown signs of activity in small cell lung cancer, but combining it with ZL-1310 (and with or without PD-L1 blockade) is a newer approach that has not yet been established.

Eligibility criteria

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.

Where this trial is running

New York, New York and 2 other locations

• New York University Cancer Institute — New York, New York, United States (Recruiting)
• Baptist Cancer Center — Memphis, Tennessee, United States (Recruiting)
• Next Virginia — Fairfax, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Amgen Call Center

Conditions Small Cell Lung Cancer; Tarlatamab; ZL-1310; Durvalumab; SCLC; Anti-PD-L1; Extensive Stage Small Cell Lung Cancer; Programmed death protein-1