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DLL3-expressing TumorsPhase 2NCT06788938

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

A Phase 2 study testing Tarlatamab treatment in people with DLL3-expressing Tumors and Advanced Tumors, run by Jonsson Comprehensive Cancer Center at 5 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
DLL3-expressing Tumors, Advanced Tumors
What is being tested?
Tarlatamab treatment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
5 sitesUnited States
Study dates
21 Mar 2025to 24 Apr 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • Adequate organ function as defined in Table 3 below. System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1.0 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL Renal Estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) ≥ 30 mL/min/1.73 m2 Hepatic Serum total bilirubin ≤ 1.5 x ULN, with the exception of participants with Gilbert's disease AST (SGOT) and ALT (SGPT) ≤ 3 x ULN≤ 5 x ULN for patients with liver metastasis or primary liver cancer Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT), and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, and then only as long as PT or PTT is within therapeutic range of intended use of anticoagulants

Who cannot join

  • 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
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  • 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.
  • Other Medical Conditions
  • History of other malignancy within the past 2 years, with the following exceptions:
  • Malignancy treated with curative intent before enrollment, with no known active disease and felt to be at low risk for recurrence by the treating physician, after discussion with the medical monitor.
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Adequately treated cervical carcinoma in situ without evidence of disease.
  • Adequately treated breast ductal carcinoma in situ without evidence of disease.
  • Prostatic intraepithelial neoplasia without evidence of prostate cancer.
  • Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
  • History of myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association, class II) within 6 months prior to first dose of study treatment.
  • History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months prior to first dose of study treatment.
  • Human immunodeficiency virus (HIV) infection.
  • Participants with HIV infection on antiviral therapy and undetectable viral load are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on study per local or institutional guidelines
  • Active hepatitis C infection.
  • Defined as participants with detectable hepatitis C antibody [HCV Ab] and hepatitis C virus [HCV] RNA viral load above the limit of quantification
  • Participants with presence of HCV antibody (HCV Ab positive) and HCV RNA viral load below the limit of quantification (HCV RNA negative) with or without prior treatment are allowed
  • Active hepatitis B infection. • Defined as presence of hepatitis B surface antigen [HBsAg-positive] and hepatitis B virus [HBV] DNA viral load above the limit of quantification [HBV DNA positive] • Participants with resolved HBV infection defined as absence of HBV surface antigen (HBsAg-negative) and presence of HBV core antibody (anti-HBc positive) followed by an HBV DNA viral load below the limit of quantification (HBV DNA negative) are allowed, with a requirement for regular monitoring for reactivation for the duration of treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines.
  • Participants with chronic HBV infection inactive carriers state, defined as presence of HBV surface antigen (HBsAg-positive) and HBV DNA viral load below the limit of quantification (HBV DNA negative) are allowed, with a requirement for regular monitoring for reactivation for the duration of treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines.
  • Participants with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of study treatment.
  • Upon completion of antibiotics and resolution of symptoms, the participant may be considered eligible for the study from an infection standpoint.
  • Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment. Participants requiring oral antibiotics who have been afebrile > 24 hours, have no leukocytosis, nor clinical signs of infection are eligible. Screening for chronic infectious conditions is not required unless otherwise noted as exclusion criteria.
  • Other Exclusions
  • Female participants of childbearing potential unwilling to use protocol specified method of contraception (see Section 5.7.2) during treatment and for an additional 60 days after the last dose of study treatment.
  • Female participants who are breastfeeding or who plan to breastfeed while on study through 60 days after the last dose of study treatment.
  • Female participants planning to become pregnant or donate eggs while on study through 60 days after the last dose of study treatment.
  • Female participants of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive serum pregnancy test.
  • Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 60 days after the last dose.
  • Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 60 days after the last dose of study treatment.
  • Male participants unwilling to abstain from donating sperm during treatment and for an additional 60 days after the last dose of study treatment.
  • Participant has known sensitivity to any of the products or components to be administered during dosing.
  • Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (e.g., Clinical Outcome Assessments) to the best of the participant's and investigator's knowledge.
  • History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.
  • -

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • UC Davis Comprehensive Cancer Center

    Davis, California, 95817

  • UCI Health Chao Family Comprehensive Cancer Center

    Irvine, California, 92612

  • University of California at Los Angeles

    Los Angeles, California, 90095

  • UC San Diego Moores Cancer Center

    San Diego, California, 92093

  • University of California at San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: Tarlatamab in Advanced DLL3-Expressing Tumors Including Neuroendocrine Neoplasms

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.

Read the detailed description

This is a phase II, multicenter, basket trial to evaluate the safety, tolerability, and efficacy of tarlatamab in DLL3-expressing tumors. The study will enroll patients with advanced tumors, other than small cell lung cancer or neuroendocrine prostate cancer, that are confirmed to exhibit DLL3 expression. Patients will be treated with tarlatamab until disease progression, death, unacceptable adverse effects, or withdrawal of consent.

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.

Being tested
Tarlatamab treatment
Keywords
tumor
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tarlatamab treatmentDrug

    • 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
Study groups in NCT06788938
Study groupRoleWhat they receive
Tarlatamab treatmentExperimentalTarlatamab will be administered as a 60-minute intravenous (IV)
Receives: Drug: Tarlatamab treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 18 months

Secondary outcomes (4)

  1. Duration of response (DOR)

    Duration of response, defined as time from the first documentation of OR until the first documentation of disease progression or death due to any cause, whichever occurs first. Only participants who have achieved OR will be evaluated for DOR

    Measured: 18 months

  2. Progression free survival (PFS)

    Progression free survival (PFS) is defined as time from randomization until disease progression based on RECIST 1.1, or death from any cause, whichever occurs first.

    Measured: 18 months

  3. Overall Survival (OS)

    OS is defined as time from randomization until death from any cause.

    Measured: 18 months

  4. Safety and tolerability

    Safety and tolerability of tarlatamab as measured by adverse events defined by Common Terminology Criteria for Adverse Events V5.0 (CTCAE 5.0). CRS and ICANS will be graded per ASTCT Consensus Grading.

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2025
  2. Study start21 Mar 2025
  3. Primary completion24 Apr 2028 (estimated)
  4. Study completion24 Apr 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
29 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06788938
Sponsor's protocol ID
24-5504
Status last verified
May 2026
First submitted
15 Jan 2025
Last updated
1 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tarlatamab treatment in people with DLL3-expressing Tumors and Advanced Tumors, run by Jonsson Comprehensive Cancer Center at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06788938.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.

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