What is an AMG 757?: The T-cell Engager Imdelltra (Tarlatamab)

October 8, 2025 •

5 min read

In May 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the immunotherapy AMG 757, now known as tarlatamab, for treating extensive-stage small cell lung cancer (SCLC). This approval marked a significant milestone, as treatment options for SCLC that has relapsed after initial chemotherapy have historically been limited.

Quick Summary

AMG 757 is a bispecific T-cell engager immunotherapy, now called tarlatamab (Imdelltra). It targets the DLL3 protein on cancer cells to redirect and activate T-cells, enabling the immune system to kill tumors in extensive-stage small cell lung cancer.

Key Points

Drug Identity: AMG 757 is the former designation for tarlatamab, commercially known as Imdelltra, an FDA-approved immunotherapy for extensive-stage small cell lung cancer.
Mechanism of Action: The drug functions as a bispecific T-cell engager (BiTE), physically connecting immune T-cells (via CD3) with tumor cells (via DLL3) to trigger a targeted immune attack.
Specific Cancer Target: It targets Delta-like Ligand 3 (DLL3), a protein highly expressed on small cell lung cancer cells, enabling precise targeting and minimizing harm to healthy tissue.
Clinical Efficacy: Clinical trials, such as the DeLLphi-301 study, demonstrated promising antitumor activity and durable responses in patients with previously treated SCLC.
Managed Side Effects: Key side effects include Cytokine Release Syndrome (CRS) and neurologic toxicity, which are managed with specific protocols during treatment.
Addressing an Unmet Need: Tarlatamab provides a new treatment option for relapsed/refractory SCLC, an aggressive cancer with a high relapse rate and poor prognosis.

What Is a Bispecific T-cell Engager (BiTE)?

A bispecific T-cell engager, or BiTE, is a type of immunotherapy that acts as a bridge between the body's immune cells and cancer cells. BiTE molecules are engineered proteins with two binding sites: one that attaches to a specific marker on cancer cells and another that binds to the CD3 protein on a T-cell, a key component of the immune system. By linking these two cell types together, the BiTE effectively redirects and activates the T-cell to attack and destroy the tumor cell. This innovative approach offers a highly targeted way to leverage the body's own defense mechanisms against cancer.

The Journey from AMG 757 to Tarlatamab (Imdelltra)

AMG 757 is the investigational name given to the drug developed by the company Amgen. During its development and clinical testing phases, it was known by this designation. Upon receiving accelerated approval from the FDA, it was assigned the official generic name tarlatamab and the brand name Imdelltra. The successful clinical development of this first-in-class BiTE was a crucial step toward its commercialization, making it available as a treatment option for patients with limited alternatives.

The Role of DLL3 in Cancer Treatment

Delta-like Ligand 3 (DLL3) is the specific target of tarlatamab. Extensive research has shown that DLL3 is a highly expressed surface protein on most small cell lung cancer (SCLC) tumors, while its presence on normal tissues is minimal. This unique expression profile makes DLL3 an ideal target for a BiTE therapy, allowing for a precise attack on cancer cells with less harm to healthy cells. The high expression of DLL3 is what makes tarlatamab a particularly promising treatment for this specific, aggressive cancer.

Mechanism of Action: How Tarlatamab Fights Cancer

The dual-binding mechanism of tarlatamab is central to its therapeutic effect. The process can be summarized in three key steps:

Tumor Cell Engagement: The anti-DLL3 binding site on the tarlatamab molecule attaches to the DLL3 protein on the surface of SCLC tumor cells, identifying them as targets.
T-cell Recruitment: Simultaneously, the anti-CD3 binding site attaches to the CD3 receptor on nearby T-cells, recruiting them to the site of the tumor.
T-cell Activation and Tumor Cell Lysis: The physical linkage and cross-linking of the T-cell and the tumor cell activate the T-cell, causing it to release cytotoxic proteins and proinflammatory cytokines. This results in the T-cell-dependent killing of the cancer cell.

Preclinical studies confirmed that tarlatamab could effectively engage T-cells and promote significant tumor regression in mouse models of SCLC. This potent and specific activity paved the way for clinical investigation.

Clinical Trial Results and Efficacy

The FDA approval of tarlatamab was based on data from the Phase II DeLLphi-301 trial, which evaluated its effectiveness in patients with previously treated extensive-stage SCLC. Key findings from this and other studies included:

Significant Antitumor Activity: Clinical trials demonstrated that tarlatamab induced tumor shrinkage and partial responses in a portion of patients who had relapsed or progressed after receiving platinum-based chemotherapy.
Durable Responses: Many responders experienced sustained periods without disease progression, indicating the durability of the treatment effect.
Acceptable Safety Profile: The drug showed a manageable safety profile at doses tested, with common side effects being reversible with supportive care.

Side Effects and Management

As with any powerful immunotherapy, tarlatamab can cause significant side effects. The most frequently observed include:

Cytokine Release Syndrome (CRS): This is the most common side effect, often presenting with flu-like symptoms such as fever, fatigue, chills, and muscle aches. Severe cases can affect multiple organs. Step-up dosing and pre-medication are used to reduce severity.
Neurologic Toxicity: Side effects such as confusion, headache, and insomnia have been reported.
Hematologic Toxicities: Decreases in blood cell counts, including neutrophils, platelets, and red blood cells (leading to anemia), are possible.
Other Common Effects: Fatigue, loss of appetite, musculoskeletal pain, and constipation are also among the commonly reported side effects.

Close monitoring by healthcare professionals is essential, particularly during the initial treatment cycles, to identify and manage these potential adverse events promptly.

Comparison: Tarlatamab vs. Conventional SCLC Therapies


Feature	Tarlatamab (Imdelltra)	Traditional Chemotherapy	Immune Checkpoint Inhibitors (e.g., PD-1/PD-L1)
Mechanism	Bispecific T-cell engager; links T-cells to tumor cells expressing DLL3.	Non-specific cytotoxic agents that kill rapidly dividing cells.	Block negative regulatory pathways to unleash immune cells.
Targeting	Highly specific for tumor cells expressing the DLL3 protein.	Broad, systemic, and non-selective killing of both healthy and cancer cells.	Can be less specific, relying on the tumor microenvironment; may have modest effects in SCLC.
Therapeutic Target	Surface marker DLL3, often overexpressed in SCLC.	DNA or cellular machinery in all dividing cells.	Negative immune checkpoints (e.g., PD-1, PD-L1).
Main Side Effects	CRS, neurologic toxicities, cytopenias.	Nausea, hair loss, fatigue, myelosuppression.	Immune-related adverse events, often involving inflammation in various organs.
Treatment Scenario	Used in previously treated extensive-stage SCLC.	First-line treatment for extensive-stage SCLC.	Can be used alone or in combination, but have shown only modest efficacy in SCLC.

Conclusion: Advancing SCLC Treatment

AMG 757, now known as tarlatamab (Imdelltra), represents a significant step forward in treating extensive-stage SCLC that has progressed despite platinum-based chemotherapy. As a novel bispecific T-cell engager targeting DLL3, it offers a directed approach to mobilize the immune system against cancer cells. The accelerated FDA approval highlights its potential to provide a meaningful new option for patients with this aggressive disease. Ongoing research aims to further explore its utility, including in combination with other therapies and potentially in other DLL3-expressing cancers.

To learn more about the FDA approval, refer to Amgen's official press release.

Key Takeaways

AMG 757 is Tarlatamab (Imdelltra): The investigational name AMG 757 is now the FDA-approved drug tarlatamab, marketed as Imdelltra, for extensive-stage SCLC.
BiTE Mechanism: Tarlatamab is a bispecific T-cell engager (BiTE) that links a patient's T-cells to cancer cells.
DLL3 Target: It specifically targets the DLL3 protein, which is prevalent on SCLC tumor cells and minimally found on healthy tissues.
Immune Activation: By binding to DLL3 on tumor cells and CD3 on T-cells, tarlatamab activates T-cells to kill cancer cells.
Clinical Success: Studies, like DeLLphi-301, showed significant anti-tumor responses and durable benefits in previously treated SCLC patients.
Manageable Side Effects: Common side effects include CRS and neurologic toxicities, requiring careful monitoring and management.
Addresses Unmet Need: Tarlatamab provides a new and targeted therapeutic option for a patient population with limited treatment alternatives.

Frequently Asked Questions

The new name for the drug formerly known as AMG 757 is tarlatamab. It is sold under the brand name Imdelltra and was approved by the FDA in May 2024 for extensive-stage small cell lung cancer.

Tarlatamab works as a bispecific T-cell engager (BiTE). It has a dual-binding mechanism, connecting a T-cell to a tumor cell. One part of the drug binds to the DLL3 protein on the tumor, and the other part binds to the CD3 protein on the T-cell, activating the T-cell to destroy the cancer cell.

AMG 757 (tarlatamab) is indicated for the treatment of adults with extensive-stage small cell lung cancer (SCLC) that has progressed on or after platinum-based chemotherapy.

Common side effects include Cytokine Release Syndrome (CRS), fatigue, pyrexia (fever), decreased appetite, and musculoskeletal pain. CRS is a particular risk that requires close monitoring and specific management strategies.

CRS is an inflammatory condition that results from the activation of the immune system by the drug. Symptoms often include fever, hypotension, and fatigue, and it is most common following the first few doses. Management includes specific pre-medications and supportive care.

Delta-like Ligand 3 (DLL3) is a protein that is highly expressed on the surface of most SCLC tumor cells, but is minimally present on healthy cells. This differential expression makes DLL3 a very specific target for the BiTE technology, allowing the drug to attack cancer cells while sparing healthy tissue.

While primarily developed for SCLC, the potential use of AMG 757 (tarlatamab) in other DLL3-expressing tumors, such as neuroendocrine prostate cancer, is being explored in clinical trials.

Tarlatamab is administered intravenously. The half-life extended (HLE) technology of the bispecific molecule allows for less frequent dosing intervals compared to standard BiTE molecules, improving patient convenience.

Tarlatamab offers a different, more targeted approach than traditional, non-selective chemotherapy, using the patient's own immune system to specifically attack DLL3-expressing tumor cells. Chemotherapy is typically a first-line treatment, while tarlatamab is used for patients whose disease has progressed.