What side effects are associated with this type of intervention?

Common treatments for Small Cell Lung Cancer (SCLC) similar to Tarlatamab and AMG 404 include bispecific T-cell engagers and anti-PD-1 monoclonal antibodies. Bispecific T-cell engagers can cause cytokine release syndrome (CRS), leading to fever, fatigue, and hypotension, as well as neurotoxicity, such as confusion or seizures. Anti-PD-1 monoclonal antibodies are associated with immune-related adverse events, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. General side effects for these treatments also include fatigue, nausea, and decreased appetite.

What prior FDA approvals exist?

For the treatment of Small Cell Lung Cancer (SCLC), the FDA has approved several immunotherapy and chemotherapy combinations. Atezolizumab, an anti-PD-L1 antibody, in combination with carboplatin and etoposide, was a significant advancement, showing improved overall survival (OS) and progression-free survival (PFS) in patients with extensive-stage SCLC. Similarly, the anti-PD-L1 antibody durvalumab combined with platinum-etoposide has also demonstrated improved survival outcomes. These treatments are comparable to the investigational combination of Tarlatamab (a bispecific T-cell engager targeting DLL3) and AMG 404 (an anti-PD-1 monoclonal antibody), which aims to enhance the immune response against SCLC.

What other types of research exist?

Promising, novel alternatives to Tarlatamab in combination with AMG 404 for Small Cell Lung Cancer patients include: 1) Atezolizumab in combination with carboplatin and etoposide, which has shown improved overall survival and progression-free survival in clinical trials. 2) Durvalumab in combination with platinum-etoposide, which has also demonstrated improved survival outcomes in the CASPIAN trial. Both of these immunotherapy-based combinations have shown efficacy and safety in the treatment of extensive-stage SCLC.

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Tarlatamab + AMG 404 for Small Cell Lung Cancer

Phase 1

Waitlist Available

Research Sponsored by Amgen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age greater than or equal to 18 years old at the same time of signing the informed consent

Participants with histologically or cytologically confirmed Small Cell Lung Cancer (SCLC) who progressed or recurred following at least 1 platinum-based regimen

Must not have

History of solid organ transplantation

Participants who experienced recurrent grade 2 pneumonitis or severe or life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents

Timeline

Screening 3 weeks

Treatment Varies

Follow Up first dose of ip up to 47 days after the last dose of ip (safety follow-up 1 [sfu1]; median duration was 3.0 months); and from the end of sfu1 up to 145 days after the last dose of ip (ep; median duration was 1.7 months)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new combination of two drugs to see if they are safe and to determine the best dose. It likely targets patients who need new treatment options. The drugs are expected to work together to improve treatment outcomes.

Who is the study for?

Adults over 18 with Small Cell Lung Cancer (SCLC) that's worsened after platinum-based therapy can join. They must be fairly active (ECOG 0-1), have treated brain metastases meeting certain conditions, proper organ function, and no recent other cancers or major surgeries. Immune system issues, untreated brain problems, or prior similar treatments disqualify them.

What is being tested?

The trial is testing the safety and best dose of tarlatamab combined with AMG 404 in treating SCLC. It aims to find out how well patients tolerate this combination and establish a recommended dosage for further studies.

What are the potential side effects?

Possible side effects include reactions related to the immune system affecting various organs, potential lung issues like pneumonitis, infusion-related reactions which could range from mild discomfort to severe responses requiring treatment discontinuation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years or older and can sign the consent form.

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My small cell lung cancer returned after platinum-based treatment.

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I can carry out all my daily activities without help.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had an organ transplant.

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I had severe side effects from immune therapy that stopped my treatment.

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I have had issues with my pituitary gland.

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I have not received tarlatamab or DLL3 x CD3 bispecific therapy before.

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I have not taken steroids or immunosuppressants in the last 7 days.

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I finished chemotherapy over 2 weeks ago and have no major side effects.

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I have lung scarring or inflammation not caused by an infection.

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I have not had major surgery within the last 4 weeks.

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I have brain metastases or leptomeningeal disease that hasn't been treated or is causing symptoms.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ first dose of ip up to 47 days after the last dose of ip (safety follow-up 1 [sfu1]; median duration was 3.0 months); and from the end of sfu1 up to 145 days after the last dose of ip (ep; median duration was 1.7 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~first dose of ip up to 47 days after the last dose of ip (safety follow-up 1 [sfu1]; median duration was 3.0 months); and from the end of sfu1 up to 145 days after the last dose of ip (ep; median duration was 1.7 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and first dose of ip up to 47 days after the last dose of ip (safety follow-up 1 [sfu1]; median duration was 3.0 months); and from the end of sfu1 up to 145 days after the last dose of ip (ep; median duration was 1.7 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Participants Who Experienced Dose-limiting Toxicity (DLT)

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Secondary study objectives

Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of Tarlatamab in Combination With AMG 404

Disease Control Rate Per Modified RECIST v1.1

Kaplan-Meier Estimate of Duration of Response Per Modified RECIST v1.1

+5 more

Side effects data

From 2024 Phase 1 trial • 23 Patients • NCT04885998

71%

Cytokine release syndrome

43%

Anaemia

29%

Vomiting

29%

Fatigue

29%

Neutropenia

29%

Upper respiratory tract infection

29%

Nausea

29%

Thrombocytopenia

14%

Oral fungal infection

14%

Constipation

14%

Atrioventricular block first degree

14%

Dry mouth

14%

Hypokalaemia

14%

Diarrhoea

14%

Infusion related reaction

14%

Mouth ulceration

14%

Hypomagnesaemia

14%

Acute respiratory distress syndrome

14%

Decreased appetite

14%

Pyrexia

14%

COVID-19

14%

Hypoalbuminaemia

14%

Hyponatraemia

14%

Flank pain

14%

Myalgia

14%

Dry skin

14%

Hypertension

14%

Oropharyngeal pain

14%

Dysgeusia

14%

Abdominal distension

14%

Sinus arrhythmia

14%

Cough

14%

Dizziness

14%

Hyperglycaemia

14%

Vitamin D deficiency

100%

80%

60%

40%

20%

Study treatment Arm

Part 2 Dose Expansion Cohort: Tarlatamab Dose B + AMG 404 (SFU1)

Part 1 Cohort 3: Tarlatamab Dose A/ Dose D + AMG 404 (SFU1)

Part 2 Dose Expansion Cohort: Tarlatamab Dose B + AMG 404 (EP)

Part 1 Cohort 2: Tarlatamab Dose A/Dose C + AMG 404 (SFU1)

Part 1 Cohort 1: Tarlatamab Dose A/Dose B + AMG 404 (SFU1)

Part 1 Cohort 1: Tarlatamab Dose A/Dose B + AMG 404 (EP)

Part 1 Cohort 2: Tarlatamab Dose A/Dose C + AMG 404 (EP)

Part 1 Cohort 3: Tarlatamab Dose A/ Dose D + AMG 404 (EP)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Phase 2: Dose ExpansionExperimental Treatment2 Interventions

Participants will receive the RP2D of tarlatamab in combination with AMG 404 identified in Phase 1 (dose exploration) of the study.

Group II: Phase 1: Dose ExplorationExperimental Treatment2 Interventions

The recommended phase 2 target dose (RP2D) of tarlatamab in combination with AMG 404 will be estimated using a modified toxicity probability interval (mTPI-2) design. A combination RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an maximum tolerated dose (MTD).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tarlatamab

2021

Completed Phase 1

~70

AMG 404

2020

Completed Phase 1

~230

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Tarlatamab, a bispecific T-cell engager, targets DLL3, a protein commonly expressed on SCLC cells, and redirects T-cells to attack these cancer cells. AMG 404, an anti-PD-1 monoclonal antibody, blocks the PD-1 pathway, enhancing the immune system's ability to detect and destroy cancer cells. These mechanisms are crucial for SCLC patients as they leverage the body's immune system to specifically target and eliminate cancer cells, potentially improving treatment efficacy and patient outcomes.

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