Tarlatamab for Small Cell Lung Cancer

(DeLLphi-301 Trial)

Not currently recruiting at 110 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Amgen

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Brain metastases, Pneumonitis, Heart failure, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a drug called tarlatamab (also known as Imdelltra, tarlatamab-dlle, AMG757, or AMG-757) for individuals with small cell lung cancer that has returned or resisted treatment. The trial examines different doses to evaluate the drug's effectiveness and its impact on tumors. Individuals whose small cell lung cancer has worsened after receiving a platinum-based treatment and at least one other therapy might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had prior anti-cancer therapy within 28 days before starting the trial, and you should not be on systemic steroid therapy or other immunosuppressive treatments within 7 days before the first dose of tarlatamab.

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

Research has shown that tarlatamab holds promise for treating small cell lung cancer, with a generally manageable safety profile. While some side effects may occur, they are usually expected and controllable.

In earlier studies, patients experienced positive results with tarlatamab in terms of both safety and effectiveness. Specifically, a 10 mg dose every two weeks demonstrated strong anti-tumor effects with lasting benefits. The treatment has been tested in various doses, and findings suggest it is safe across different groups.

Although all treatments can have side effects, evidence so far indicates that tarlatamab's side effects are generally manageable. This makes it a potential option for those considering joining a clinical trial for small cell lung cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for small cell lung cancer?

Unlike the standard treatments for small cell lung cancer, which typically involve chemotherapy and radiation, Tarlatamab offers a novel approach by engaging the immune system to fight cancer. Tarlatamab is unique because it is a bispecific T-cell engager (BiTE) antibody construct that redirects T-cells to target and destroy cancer cells. Researchers are excited about Tarlatamab because its mechanism of action could offer a more targeted and potentially less toxic treatment option compared to traditional therapies. This innovative approach may lead to better outcomes and improved survival rates for patients with this challenging form of lung cancer.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

Research shows that tarlatamab may effectively treat small cell lung cancer (SCLC). Studies have found that administering tarlatamab every two weeks can significantly reduce tumor size for an extended period. Additionally, tarlatamab has helped patients live longer compared to traditional chemotherapy, particularly for those whose cancer has returned after initial treatments. In this trial, participants will receive different doses of tarlatamab to evaluate its effectiveness and safety. Tarlatamab is a type of medicine that helps the body's immune system target and attack cancer cells. These findings suggest tarlatamab could be a promising option for people with SCLC. ^{1 3 6 7 8}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed/refractory Small Cell Lung Cancer (SCLC) who have tried at least one platinum-based therapy and another treatment. They must have a life expectancy of at least 12 weeks, measurable cancer lesions, and be in fairly good health (ECOG status of 0 or 1). Participants with treated brain metastases may join if they meet certain criteria. Pregnant women, those planning to become pregnant, or breastfeeding are excluded, as well as anyone unwilling to use contraception.

Inclusion Criteria

My small cell lung cancer has come back or didn't respond to treatment.

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

My cancer returned or worsened after 1 platinum-based treatment and another therapy.

Exclusion Criteria

Other Medical Conditions

History or evidence of any other clinically significant disorder, condition or disease determined by the investigator or Amgen physician.

I cannot find someone to stay with me for 72 hours after my first two tarlatamab treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive either a low or high dose of Tarlatamab to evaluate safety and efficacy

8 weeks

Weekly visits for monitoring

Treatment Part 2

Participants receive the selected target dose of Tarlatamab based on findings in Part 1

8 weeks

Bi-weekly visits for monitoring

Treatment Part 3

Participants receive the selected target dose of Tarlatamab with reduced Cycle 1 monitoring requirements

4 weeks

Reduced monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Monthly visits

What Are the Treatments Tested in This Trial?

Interventions

• Tarlatamab

Trial Overview The study tests two dose levels of Tarlatamab for safety and effectiveness against SCLC tumors. It's divided into parts: the first evaluates safety/effectiveness per RECIST 1.1 standards; the second assesses tumor response rate by independent review; the third looks at safety regarding reduced monitoring after initial doses.

How Is the Trial Designed?

Group I: Part 3: Modified Monitoring Substudy Experimental Treatment 1 Intervention

Participants will receive the selected target dose of Tarlatamab based on findings in Part 1 with reduced Cycle 1 monitoring requirements.

Group II: Part 2: Dose Expansion Experimental Treatment 1 Intervention

Participants will receive the selected target dose of Tarlatamab based on findings in Part 1.

Group III: Part 1: Tarlatamab Low Dose Experimental Treatment 1 Intervention

Participants will receive the low dose of Tarlatamab.

Group IV: Part 1: Tarlatamab High Dose Experimental Treatment 1 Intervention

Participants will receive the high dose of Tarlatamab.

Tarlatamab is already approved in United States for the following indications:

Approved in United States as Imdelltra for:

• Extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy

Who Is Running the Clinical Trial?

Amgen

Lead 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 phase 2 trial involving 220 patients with previously treated small-cell lung cancer, tarlatamab demonstrated significant antitumor activity, with an objective response rate of 40% in the 10-mg group and 32% in the 100-mg group, indicating its potential as an effective treatment option.

The treatment was generally well-tolerated, with the most common side effects being cytokine-release syndrome, which was mostly mild (grade 1 or 2), and only 3% of patients discontinued due to treatment-related adverse events, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. Ahn, MJ., Cho, BC., Felip, E., et al.[2023]

Delta-like ligand 3 (DLL3) is a promising therapeutic target in small cell lung cancer (SCLC) due to its high expression in SCLC tumors and low expression in normal tissues, which may reduce treatment-related toxicities.

Several DLL3-targeted therapies, including the antibody-drug conjugate rovalpituzumab tesirine and bispecific T cell engager AMG 757, are being developed and show potential for improving treatment outcomes in patients with recurrent or refractory SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DLL3: an emerging target in small cell lung cancer. Owen, DH., Giffin, MJ., Bailis, JM., et al.[2020]

AMG 757 demonstrated strong antitumor activity against small-cell lung cancer (SCLC) by effectively targeting DLL3, leading to significant tumor regression and complete responses in mouse models, even in cases with low DLL3 expression.

The treatment was well tolerated in nonhuman primates, showing no adverse effects at the highest tested dose, and its extended half-life suggests it could allow for less frequent dosing in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer. Giffin, MJ., Cooke, K., Lobenhofer, EK., et al.[2023]

DLL3 is a promising target for treating small cell lung cancer (SCLC) due to its overexpression on cancer cells and minimal presence on normal cells, making it a potential avenue for targeted therapies.

While the DLL3-targeting antibody-drug conjugate Rova-T was halted in phase 3 trials due to lack of efficacy, ongoing development of other DLL3-targeting therapies, such as T-cell engagers and CAR T-cell therapies, shows potential for improving treatment outcomes in SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer. Rudin, CM., Reck, M., Johnson, ML., et al.[2023]

Tarlatamab is a promising investigational treatment for small cell lung cancer, specifically targeting the delta-like ligand 3 protein, and has shown effectiveness in patients whose cancer progressed after previous therapies.

Despite its potential benefits, there are concerns regarding the administration challenges of tarlatamab, which may affect its acceptance by clinicians and patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tarlatamab Shows Promise in SCLC. [2023]

Tarlatamab, a bispecific T-cell engager targeting DLL3 in small-cell lung cancer (SCLC), showed a manageable safety profile with 90.7% of patients experiencing treatment-related adverse events, including cytokine release syndrome in 52% of patients.

The treatment demonstrated an objective response rate of 23.4% and a median duration of response of 12.3 months, indicating promising antitumor activity in heavily pretreated SCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study. Paz-Ares, L., Champiat, S., Lai, WV., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40280845/

Real-World Outcomes of Tarlatamab in Small Cell Lung ... Tarlatamab is a promising treatment option for heavily pretreated small cell lung cancer patients. We observed higher rates of CRS and ICANS during the first ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2307980

Tarlatamab for Patients with Previously Treated Small-Cell ... Tarlatamab, administered as a 10-mg dose every 2 weeks, showed antitumor activity with durable objective responses and promising survival outcomes

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04885998

AMG 757 and AMG 404 in Subjects With Small Cell Lung ... A combination RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an maximum tolerated dose (MTD).

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40454646/

Tarlatamab in Small-Cell Lung Cancer after Platinum- ... Treatment with tarlatamab led to longer overall survival than chemotherapy among patients with small-cell lung cancer whose disease had progressed during or ...

5. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-472794

Taking a Bite Out of Small Cell Lung Cancer By Leveraging ... Tarlatamab is a bispecific T-cell engager (BiTE) that binds to delta-like ligand-3 (DLL3) on small cell lung cancer (SCLC) cells and cluster of differentiation ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33203642/

AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific ... AMG 757 has a compelling safety and efficacy profile in preclinical studies making it a viable option for targeting DLL3-expressing SCLC tumors in the clinical ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.8510

Updated results from a phase 1 study of AMG 757, a half- ... Here, updated safety, efficacy, and pharmacokinetic data from 10 cohorts from the ongoing phase 1 study of AMG 757 in SCLC are reported ( ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1556086422004038

OA12.05 Phase 1 Updated Exploration and First ... Tarlatamab has an expected and manageable safety profile and delivers promising efficacy with excellent response durability amongst confirmed responders.