Tarlatamab for Small Cell Lung Cancer

(DeLLphi-304 Trial)

Recruiting at 243 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must not be taking: Corticosteroids, Immunosuppressants, CYP3A inhibitors, others

Disqualifiers: CNS metastases, Autoimmune disease, Heart failure, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

509 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting the study. Specifically, you must not use medications that affect certain liver enzymes (CYP3A) or transporters (P-gp, BCRP) within 7 to 28 days before the first dose, depending on the medication. Check with the study team to see if your current medications are affected.

What data supports the effectiveness of the drug Tarlatamab for Small Cell Lung Cancer?

Tarlatamab has shown promising activity in patients with small cell lung cancer whose disease had progressed after receiving another therapy, indicating its potential effectiveness. Additionally, Lurbinectedin, another component of the treatment, was approved by the FDA as a therapy for small cell lung cancer, supporting its use in this context. ^{1 2 3 4 5}

Is Tarlatamab safe for humans?

Tarlatamab, also known as AMG 757, is being studied for its safety in treating small cell lung cancer. While it shows promise, there are still questions about its administration, and more research is needed to fully understand its safety profile. ^{1 2 6 7 8}

What makes the drug Tarlatamab for Small Cell Lung Cancer unique?

Tarlatamab for Small Cell Lung Cancer is unique because it combines lurbinectedin, an oncogenic transcription inhibitor approved for SCLC, with topotecan, the only FDA-approved second-line treatment for SCLC, offering a novel combination approach for patients who have progressed after initial chemotherapy. ^{1 5 6 9 10}

What is the purpose of this trial?

This trial is testing a new treatment called tarlatamab to see if it helps patients live longer. Tarlatamab works by boosting the immune system to better fight cancer. The goal is to find out if this new treatment can improve overall survival for these patients.

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

Adults with relapsed/refractory Small Cell Lung Cancer (SCLC) who've had one platinum-based treatment can join. They need a life expectancy of at least 12 weeks, measurable disease, and good organ function. Exclusions include untreated brain metastases, recent serious heart issues or strokes, certain infections or treatments, pregnancy/breastfeeding individuals, and those unwilling to use contraception.

Inclusion Criteria

My small cell lung cancer has worsened or returned after treatment.

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

I am at least 18 years old or considered an adult in my country.

Exclusion Criteria

I am a woman able to have children and agree to use birth control as required.

I've had side effects from immune therapy as outlined in the study.

Presence or history of viral infection based on criteria per protocol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tarlatamab as an IV infusion or standard of care chemotherapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lurbinectedin
• Tarlatamab
• Topotecan

Trial Overview The trial is testing Tarlatamab against standard chemotherapy drugs like Lurbinectedin, Topotecan, and Amrubicin in patients with SCLC that has come back after treatment. The goal is to see if Tarlatamab helps patients live longer compared to the usual treatments.

Participant Groups

Group I: Tarlatamab Experimental Treatment 1 Intervention

Participants will receive tarlatamab as an intravenous (IV) infusion.

Group II: Standard of Care Active Control 3 Interventions

Participants will receive treatment per local standard of care (SOC).

Lurbinectedin is already approved in United States, European Union for the following indications:

Approved in United States as Zepzelca for:

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

Approved in European Union as Zepzelca for:

• Metastatic small-cell lung cancer (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

Findings from Research

Lurbinectedin, approved by the FDA in June 2020 as ZEPZELCA, is the first systemic therapy specifically for Small Cell Lung Cancer (SCLC), highlighting its significance in cancer treatment.

The drug works by inhibiting the transcription of genes related to tumor growth, which helps to suppress tumor-associated macrophages and alter the tumor environment, making it a promising option for SCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Small Cell Lung Cancer with Lurbinectedin: A Review. Rajput, PS., Khan, SR., Singh, P., et al.[2022]

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]

Belotecan showed a higher objective response rate (33%) compared to topotecan (21%) and a significantly longer median overall survival (13.2 months vs. 8.2 months), suggesting it may be a more effective treatment for sensitive-relapsed small-cell lung cancer (SCLC).

Patients receiving belotecan also had a higher completion rate of treatment cycles (53% vs. 35%), indicating better tolerability and potential for improved patient adherence compared to topotecan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer. Kang, JH., Lee, KH., Kim, DW., et al.[2021]

In a phase II trial involving 120 patients with extensive-stage small cell lung cancer, the combination of paclitaxel, carboplatin, and etoposide showed a significantly higher overall response rate of 78% compared to 48% for the paclitaxel and topotecan combination.

The paclitaxel-carboplatin-etoposide regimen also resulted in a longer median time to progression (7.6 months) compared to the paclitaxel-topotecan group (5.5 months), indicating it may be a more effective initial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin/etoposide versus paclitaxel/topotecan for extensive-stage small cell lung cancer: a Minnie Pearl Cancer Research Network randomized, prospective phase II trial. Greco, FA., Thompson, DS., Morrissey, LH., et al.[2015]

Lurbinectedin (ZEPZELCA™) has been approved in the USA for treating adult patients with metastatic small cell lung cancer (SCLC) who have progressed after platinum-based chemotherapy, highlighting its efficacy in a challenging cancer type.

The drug has received orphan drug status in multiple countries, indicating its potential importance in treating rare cancers, and ongoing clinical investigations are exploring its use in other solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lurbinectedin: First Approval. Markham, A.[2021]

Lurbinectedin has a manageable safety profile when used at the approved dose of 3.2 mg/m2 every 3 weeks, as shown in a pooled analysis of 554 patients with various advanced solid tumors, including small cell lung cancer and ovarian cancer.

The most common side effects were transient hematological abnormalities, particularly neutropenia (41%) and leukopenia (30%), along with non-hematological issues like fatigue (63%) and nausea (57%), indicating that while side effects are present, they are generally manageable for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. Leary, A., Oaknin, A., Trigo, JM., et al.[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]

Topotecan combined with either cisplatin or etoposide showed similar efficacy in treating untreated extensive disease small-cell lung cancer (ED SCLC), with response rates of 63.4% for the T/C group and 61.0% for the T/E group, indicating both combinations are effective treatment options.

While both regimens had similar overall deliverability, the T/C combination resulted in significantly higher rates of severe anemia (46.4%) compared to T/E (20%), suggesting that T/E may have a better safety profile regarding hematological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised phase II study of the efficacy and safety of intravenous topotecan in combination with either cisplatin or etoposide in patients with untreated extensive disease small-cell lung cancer. Quoix, E., Breton, JL., Gervais, R., et al.[2013]

Topotecan is currently the only FDA-approved second-line treatment for small-cell lung cancer, which is crucial since most patients relapse after initial therapy despite a high response rate of up to 90%.

While other agents like vinorelbine and irinotecan have shown modest efficacy, recent research has focused on optimizing topotecan dosing and exploring combination therapies, balancing increased activity with the need to manage toxicity and maintain quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line treatment of small-cell lung cancer. MacCallum, C., Gillenwater, HH.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of Small Cell Lung Cancer with Lurbinectedin: A Review. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Tarlatamab Shows Promise in SCLC. [2023]

3. England pubmed.ncbi.nlm.nih.gov

A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

A multi-center phase II study of weekly topotecan as second-line therapy for small cell lung cancer. [2013]

5. England pubmed.ncbi.nlm.nih.gov

Paclitaxel/carboplatin/etoposide versus paclitaxel/topotecan for extensive-stage small cell lung cancer: a Minnie Pearl Cancer Research Network randomized, prospective phase II trial. [2015]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Lurbinectedin: First Approval. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. [2023]

8. United States 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. [2023]

9. Ireland pubmed.ncbi.nlm.nih.gov

A randomised phase II study of the efficacy and safety of intravenous topotecan in combination with either cisplatin or etoposide in patients with untreated extensive disease small-cell lung cancer. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Second-line treatment of small-cell lung cancer. [2019]