Tarlatamab in Advanced Delta-like 3 (DLL3)-Expressing Tumors Including Neuroendocrine Neoplasms

NCT06788938 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-5504
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 5

Brief Summary

This study is being done to learn more about the drug tarlatamab in people with your condition. The purpose of this study is to see the efficacy (how well something works) of study treatment (tarlatamab) and whether it causes any side effects. Tarlatamab is being developed as an anti-cancer drug for tumors and is FDA-approved for extensive-stage small cell lung cancer. Tarlatamab is investigational for the purpose of this study.

Conditions

DLL3-expressing Tumors; Advanced Tumors

Keywords

tumor

Outcome Measures

Primary Outcomes (1)

• 1. Primary efficacy endpoint is overall response rate (ORR) as defined as complete response (CR) or partial response (PR) by RECIST 1.1 criteria. This is evaluated in the response evaluable set of patients.

  18 months

Secondary Outcomes (4)

• Duration of response (DOR)

  18 months

• Progression free survival (PFS)

  18 months

• Overall Survival (OS)

  18 months

• Safety and tolerability

  18 months

Other Outcomes (2)

• Biomarker analysis

  18 months

• Evaluate radiologic correlates

  18 months

Study Arms (1)

Tarlatamab treatment

EXPERIMENTAL

Tarlatamab will be administered as a 60-minute intravenous (IV)

Drug: Tarlatamab treatment

Interventions

Tarlatamab treatment DRUG

* 1 mg step dose on cycle 1 day 1 (C1D1) * 10 mg target dose on cycle 1 day 8 (C1D8), and cycle 1 day 15 (C1D15) in a 28-day cycle. * 10 mg Q2W subsequently (i.e., C2 + D1/D15 dosing) in a 28-day cycle

Tarlatamab treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Participant has provided informed consent prior to initiation of any study specific activities/procedures.
• Male or female ≥ 18 years of age and willing and able to provide informed consent.
• Histologically or cytologically confirmed malignancy other than de novo (i.e., non-transformed) SCLC or NEPC. Must be stage IV (metastatic); participants with stage III disease are eligible provided that they are not candidates for surgery and/or radiotherapy with curative intent. Acceptable tumor types include the following:
• Low and intermediate grade neuroendocrine carcinoma (including carcinoid and atypical carcinoid)
• Gastroenteropancreatic NEN
• Large cell neuroendocrine carcinoma
• SCLC transformed from previously-treated NSCLC
• Extrapulmonary small cell carcinoma, with the exception of NEPC
• Any other tumor type that meets staging and DLL3 positivity criteria
• Positive DLL3 expression by immunohistochemistry on tumor biopsy.
• Positive DLL3 expression, for purposes of this study, defined as at least 25% for participants enrolling into Stage 1 or 1% for participants enrolling into Stage 2.
• Participants must have progressed on or following at least one line of therapy, if a standard of care therapy exists for the tumor type.
• Measurable disease, as per RECIST 1.1
• ECOG performance status of 0-1.

You may not qualify if:

• Disease Related
• Diagnosis of SCLC (with the exception of SCLC transformed from previously-treated NSCLC) or NEPC.
• Tumor specimen is not evaluable for DLL3 expression or tumor has DLL3 surface expression \< 1% by immunohistochemistry.
• Progressive or symptomatic brain metastases. Brain metastases that have been radiated, are asymptomatic, and on a stable or decreasing dose of steroids are allowed. Leptomeningeal disease is excluded.
• Evidence of interstitial lung disease or active, non-infectious pneumonitis. Exception: pneumonitis related to prior radiation therapy that is grade 1 and stable or improving without treatment.
• Prior/Concomitant Therapy
• Concurrent enrollment in another clinical study, unless enrolled only in the follow-up period or an observational study. Use of any investigational anticancer therapy must not have been received within 28 days prior to the first dose of study drugs.
• Any chemotherapy, antibody drug conjugate or immunotherapy for cancer treatment in the prior 21 days, or small molecular inhibitor in the prior 7 days.
• Stereotactic, palliative radiation for symptomatic bone metastases is acceptable without a washout.
• Stereotactic brain radiation for asymptomatic brain metastases is acceptable with a 7-day washout.
• Prior therapy with any selective inhibitor of the DLL3 pathway.
• Prior history of severe or life-threatening events from any immune-mediated therapy.
• Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment. Low-dose corticosteroids (prednisone ≤ 10 mg per day or equivalent is permitted)
• Major surgical procedures within 28 days prior to first dose of study treatment.
• Treatment with live virus, including live-attenuated vaccination, within 14 days prior to the first dose of study treatment. Inactive vaccines (e.g., non-live or non-replicating agent) and live viral non-replicating vaccines within 3 days prior to first dose of study treatment.

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Amgen: collaborator

Study Sites (5)

UC Davis Comprehensive Cancer Center

Davis, California, 95817, United States

RECRUITING

UCI Health Chao Family Comprehensive Cancer Center

Irvine, California, 92612, United States

RECRUITING

University of California at Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

UC San Diego Moores Cancer Center

San Diego, California, 92093, United States

RECRUITING

University of California at San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Neoplasms

Study Officials

• Jonathan Goldman, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CRU Hotline

CONTACT

888-798-0719; istteam@mednet.ucla.edu

CRU Direct line

CONTACT

310-206-2632

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A Simon's two-stage optimum design will be used \[1\]. The primary objective of this phase II trial is the overall response rate (ORR, as defined by confirmed complete and partial response) per RECIST v1.1 criteria. Our null hypothesis is an ORR of 10% or lower, based on the requirements for prior therapies, and our alternative hypothesis is an ORR of 30% or greater. We will utilize a Simon two-stage design, in which 10 patients will be entered into the first stage. If 2 or more patients show a response, then an additional 19 patients will be enrolled. If 6 or more patients out of 29 show a response, then the trial will reject the null hypothesis.

Study Record Dates

• First Submitted: January 15, 2025
• First Posted: January 23, 2025
• Study Start: March 21, 2025
• Primary Completion (Estimated): April 24, 2028
• Study Completion (Estimated): April 24, 2029
• Last Updated: March 20, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)