Tarlatamab for Neuroendocrine Tumors

Recruiting at 4 trial locations

Overseen By Ruth Gonzalez

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: SCLC, NEPC, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, tarlatamab, to evaluate its effectiveness against neuroendocrine tumors, a type of cancer originating in hormone-producing cells. Although already approved for certain lung cancers, researchers aim to determine its efficacy for other tumor types and monitor any side effects. This trial suits individuals with advanced neuroendocrine tumors who have not responded to other treatments. Participants must have a specific protein (DLL3) in their tumors, identified through a special test. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received any investigational anticancer therapy within 28 days, chemotherapy or immunotherapy within 21 days, or small molecular inhibitors within 7 days before starting the study treatment.

Is there any evidence suggesting that tarlatamab is likely to be safe for humans?

Research has shown that tarlatamab has been tested in patients with neuroendocrine tumors, and all patients experienced some side effects. These side effects, known as treatment-emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs), are common in new cancer treatments. Importantly, the FDA has already approved tarlatamab for a type of lung cancer, indicating that its safety is generally understood and manageable. However, since this study focuses on neuroendocrine tumors, tarlatamab remains experimental for this use. Researchers are still learning about its effects and safety in this specific context. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tarlatamab is unique because it targets neuroendocrine tumors through a novel mechanism of action. While most treatments for these tumors, such as somatostatin analogs and chemotherapy, work by slowing tumor growth or killing rapidly dividing cells, Tarlatamab is an investigational agent that engages the immune system to attack and destroy cancer cells. Researchers are excited about Tarlatamab because its targeted approach could offer a more effective and potentially less toxic alternative to existing therapies, which often come with significant side effects. Additionally, Tarlatamab is administered intravenously, which might enhance its ability to precisely target tumor cells.

What evidence suggests that tarlatamab might be an effective treatment for neuroendocrine tumors?

Research has shown that tarlatamab, which participants in this trial will receive, may help treat certain tumors. In studies, individuals with tumors containing a specific protein called DLL3 responded better to the treatment. Specifically, 22.2% of these patients experienced tumor shrinkage, which is encouraging. Overall, the drug appears promising for individuals with neuroendocrine tumors, especially when this protein is present. ^{1 2 5 6 7}

Who Is on the Research Team?

Jonathan Goldman, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced tumors expressing DLL3, including small cell lung cancer and neuroendocrine tumors. Participants must have stage IV disease or inoperable stage III, an ECOG performance status of 0-1, measurable disease per RECIST 1.1 criteria, and adequate organ function. They should have progressed after at least one therapy line if standard care exists for their tumor type.

Inclusion Criteria

My cancer is confirmed stage IV, or stage III and not suitable for surgery or radiotherapy.

I am fully active or can carry out light work.

Participant has provided informed consent prior to initiation of any study specific activities/procedures

Exclusion Criteria

I haven't taken steroids or immunosuppressants in the last week.

I haven't had any other cancer besides this one in the last 2 years.

I haven't received any live vaccines in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tarlatamab intravenously until disease progression, death, unacceptable adverse effects, or withdrawal of consent

18 months

Regular visits for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Tarlatamab

Trial Overview

The trial is testing the efficacy and safety of tarlatamab as a treatment for cancers that express the protein DLL3. Tarlatamab is an investigational anti-cancer drug approved for extensive-stage small cell lung cancer but being studied further in this trial.

How Is the Trial Designed?

Group I: Tarlatamab treatment Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

In a study involving 242 patients with advanced neuroendocrine tumors treated with surufatinib, the presence of treatment-related adverse events (TRAEs) like hypertension, proteinuria, and hemorrhage in the first 4 weeks was linked to a longer progression-free survival (PFS) of 11.1 months compared to 9.2 months for those without these events.

The findings suggest that TRAEs could serve as potential biomarkers for predicting the efficacy of surufatinib treatment, indicating that patients experiencing these side effects may have better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events as predictive biomarkers of efficacy in patients with advanced neuroendocrine tumors treated with surufatinib: results from two phase III studies. Li, J., Cheng, Y., Bai, C., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12434391/

Safety and Efficacy of Tarlatamab in Patients with ...

An analysis of tumor response by DLL3 expression (H-score) revealed a general trend associating greater tumor reduction with DLL3 expression (Fig. 2B). ...

2.

aacrjournals.org

aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-25-1211/763701

Safety and Efficacy of Tarlatamab in patients ... - AACR Journals

Patients with DLL3+ tumors (vs patients with DLL3-/DLL3 unknown tumors) acheived a higher ORR (22.2% [95% CI, 6.4–47.6] vs 0% [95% CI, 0–15.4]) ...

3.

onclive.com

onclive.com/view/tarlatamab-demonstrates-early-safety-and-activity-in-dll3-neuroendocrine-prostate-cancer

Tarlatamab Demonstrates Early Safety and Activity in ...

Tarlatamab showed a 10.5% objective response rate in NEPC, with better outcomes in DLL3-positive tumors, achieving a 22.2% response rate.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06788938

Study Details | NCT06788938 | Tarlatamab in Advanced ...

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 ...

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5012

Phase 1b study of tarlatamab in de novo or treatment ...

As of 24 January 2024, ORR in DLL3+ pts was 22.2% (95% CI, 6.4, 47.6); durations of response in the 4 pts with response were 25.8 m, 9.2 m, 5.5 ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S1556086425019987

P3.13.12 Multi-Institution Analysis Evaluating Safety ...

This novel therapy has demonstrated promising antitumor activity and durable objective responses in phase I/II clinical trials, however, is also associated with ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07061080

Study Details | NCT07061080 | Refractory Advanced ...

In addition, the protocol establishes an initial safety cohort composed of the first six patients included in the FOLFIRI + tarlatamab group to determine ...