BI 764532 + Standard Care for Small Cell Lung Cancer

(DAREONᵀᴹ-8 Trial)

Not currently recruiting at 28 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must be taking: Chemotherapy, Immunotherapy

Must not be taking: Investigational drugs

Disqualifiers: Leptomeningeal carcinomatosis, Recent major surgery, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 23 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the highest safe dose of a new drug, BI 764532, when combined with standard treatments to boost the immune system against extensive-stage small cell lung cancer. Participants receive BI 764532 with standard care drugs through infusions. This study targets individuals with advanced small cell lung cancer who have not yet undergone chemotherapy or immunotherapy for this stage. Regular visits to the study site are necessary to monitor health and treatment effects. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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 any systemic anti-cancer therapy or investigational drug within 28 days before starting the trial treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BI 764532, also known as obrixtamig, has been tested in patients before. Studies found it was generally well-tolerated at doses of at least 90 micrograms per kilogram, meaning most people did not experience serious side effects at these levels. Reports of tumor reduction suggest the treatment may be effective against cancer.

This is an early-stage trial, so researchers are still assessing the treatment's safety in humans. However, early results from previous studies are encouraging, indicating that many patients can tolerate the treatment well.

In this trial, BI 764532 is used alongside standard cancer treatments like chemotherapy and immunotherapy. These treatments are common, and their side effects are well-known. The goal is to determine how much BI 764532 can be administered without problems. Regular check-ups and tests monitor any issues that might arise during the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI 764532 because it introduces a new approach to treating small cell lung cancer (SCLC). Unlike traditional chemotherapy that targets rapidly dividing cells, BI 764532 is designed to work synergistically with standard chemotherapy drugs like carboplatin, etoposide, and immunotherapy agents such as atezolizumab and durvalumab. This combination aims to enhance the overall effectiveness by potentially improving the immune response against cancer cells. Additionally, the trial is exploring different dosing strategies to optimize its efficacy and safety, which could lead to more personalized treatment options for patients with SCLC.

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

Research has shown that BI 764532, also known as obrixtamig, may help treat small cell lung cancer (SCLC). Studies have found that it targets a protein called DLL3, present on many cancer cells, and aids the immune system in attacking these cells. Previous results showed that about 26% of patients with SCLC experienced tumor shrinkage, meaning roughly one in four patients saw their tumors get smaller. This trial will explore different doses of BI 764532 in combination with standard treatments like carboplatin, etoposide, atezolizumab, and durvalumab. Additionally, the treatment is known for having manageable side effects, which is important for maintaining a good quality of life. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

Adults with advanced small cell lung cancer who can receive standard chemotherapy and anti-PD-L1 immunotherapy. They must be over 18, able to consent, have a performance status of 0-1 (which means they are fully active or restricted in physically strenuous activity but ambulatory), and have not had prior treatment for extensive-stage SCLC.

Inclusion Criteria

I have signed the consent form for this trial.

I am eligible for treatment with etoposide, carboplatin or cisplatin, and atezolizumab or durvalumab.

I am eligible for treatment with carboplatin, etoposide, and atezolizumab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BI 764532 combined with standard of care treatments (chemotherapy and anti-PD-L1 immunotherapy) as intravenous infusions. The treatment is given for the entire duration of the study if tolerated.

up to 23 months

Regular visits depending on treatment response

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 764532

Trial Overview The trial is testing the highest tolerable dose of BI 764532, an antibody-like molecule that might boost the immune system's ability to fight cancer. It's given with standard treatments as infusions into a vein. The study measures how well patients tolerate this combination therapy.

How Is the Trial Designed?

Group I: Part B - Dose expansion: BI 764532 + cisplatin + etoposide + durvalumab Experimental Treatment 4 Interventions

Group II: Part B - Dose expansion: BI 764532 + carboplatin + etoposide + durvalumab Experimental Treatment 4 Interventions

Group III: Part B - Dose expansion: BI 764532 + carboplatin + etoposide + atezolizumab Experimental Treatment 4 Interventions

Group IV: Part A - Dose escalation: BI 764532 very low dose + carboplatin + etoposide + atezolizumab Experimental Treatment 4 Interventions

Group V: Part A - Dose escalation: BI 764532 medium dose + carboplatin + etoposide + atezolizumab Experimental Treatment 4 Interventions

Group VI: Part A - Dose escalation: BI 764532 low dose + carboplatin + etoposide + atezolizumab Experimental Treatment 4 Interventions

Group VII: Part A - Dose escalation: BI 764532 high dose + carboplatin + etoposide + atezolizumab Experimental Treatment 4 Interventions

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

For limited small-cell lung cancer (SCLC), the best treatment is a combination of platinum-based chemotherapy and early concurrent thoracic radiotherapy using a hyperfractionated regimen.

In Japan, the standard treatment for extensive SCLC involves a combination of irinotecan and cisplatin, with ongoing hopes for new molecular-targeted therapies to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of small cell lung cancer]. Negoro, S.[2018]

In a study of 4408 patients with small cell lung cancer (SCLC), cisplatin did not show a survival advantage over carboplatin for either extensive-stage (ES-SCLC) or limited-stage (LS-SCLC) disease, indicating that both treatments are similarly effective.

Carboplatin's favorable toxicity profile makes it a suitable option for both LS-SCLC and ES-SCLC, potentially allowing for better integration with new treatment strategies in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Carboplatin With Cisplatin in Small Cell Lung Cancer in US Veterans. Azar, I., Yazdanpanah, O., Jang, H., et al.[2023]

The ECI regimen, which combines irinotecan, cisplatin, and etoposide over three days, demonstrated a high response rate of 77% in advanced-stage small-cell lung cancer patients, indicating its efficacy as a treatment option.

The maximum tolerated dose of irinotecan was established at 140 mg/m², with manageable side effects including febrile neutropenia and grade 3 diarrhea, suggesting that the regimen is well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of etoposide, cisplatin and irinotecan triplet in patients with advanced-stage small-cell lung cancer. Briasoulis, E., Samantas, E., Kalofonos, H., et al.[2018]

Recent phase III trials have shown that adding immunotherapy (specifically anti-PD-L1 antibodies like atezolizumab and durvalumab) to standard platinum-doublet chemotherapy significantly improves overall survival for patients with extensive-stage small cell lung cancer (SCLC).

This marks the first significant advancement in survival outcomes for SCLC in over 30 years, establishing new standards of care that offer hope for better treatment results in this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dashing Decades of Defeat: Long Anticipated Advances in the First-line Treatment of Extensive-Stage Small Cell Lung Cancer. Armstrong, SA., Liu, SV.[2021]

Small cell lung cancer (SCLC) is highly sensitive to chemotherapy and radiation, with the standard treatment being a combination of platinum and etoposide, which is more effective when combined with thoracic radiotherapy (TRT), increasing survival by about 5%.

Prophylactic cranial radiation can prevent central nervous system recurrence and improve survival, while other novel agents like bevacizumab are showing promise and are under further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small cell lung cancer. Sher, T., Dy, GK., Adjei, AA.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00363

Phase I Dose-Escalation Results for the Delta-Like Ligand ... We report phase I results for obrixtamig (BI 764532), a delta-like ligand 3 (DLL3)/CD3 IgG-like T-cell engager, in patients with previously ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04429087

NCT04429087 | A Study to Test Different Doses of BI ... This study is open to adults with small cell lung cancer and other neuroendocrine cancers that are positive for the tumour marker delta-like 3 (DLL3).

3. onclive.com onclive.com/view/bi-764532-shows-early-efficacy-manageable-tolerability-in-dll3-sclc-and-neuroendocrine-carcinoma

BI 764532 Shows Early Efficacy, Manageable Tolerability ... When broken down my disease entity, BI 764532 elicited an ORR of 26% in those with SCLC (n = 39), 19% in those with extrapulmonary ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT329025

A phase I, open-label, dose-escalation trial of BI 764532 ... BI 764532 is a delta-like ligand 3 (DLL3)/CD3 T cell engaging bispecific antibody. DLL3 is expressed on the cell surface of many SCLC and NEC tumors, but not ...

5. aacrjournals.org aacrjournals.org/mct/article/22/12_Supplement/LB_A16/730466/Abstract-LB-A16-DareonTM-5-An-open-label-Phase-II

Dareon TM -5: An open-label Phase II trial of BI 764532, a ... BI 764532, a humanized IgG-like T cell engager, binds to DLL3-positive tumor cells and CD3 on T-cells and promotes T cell-mediated cytotoxicity.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35815644/

Phase I trial of the DLL3/CD3 bispecific T-cell engager BI ... The bispecific DLL3/CD3 T-cell engager BI 764532 has been shown to induce complete tumor regression in a human T cell-engrafted mouse model.

7. onclive.com onclive.com/view/dose-optimization-continues-after-preliminary-efficacy-safety-signals-with-bi-764532-in-dll3-sclc

Dose Optimization Continues After Preliminary Efficacy ... Treatment with at least 90 μg/kg of the novel DLLC-targeting T-cell–engager BI 764532 was well tolerated and led to tumor shrinkage in patients ...