BI 764532 + Topotecan for Small Cell Lung Cancer

Recruiting at 17 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Steroids, Anti-epileptics

Disqualifiers: Brain metastases, Leptomeningeal carcinomatosis, others

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

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with extensive stage small cell lung cancer, particularly those whose cancer has returned or worsened after platinum-based chemotherapy. The main goal is to determine the highest safe dose of a new drug, BI 764532, when combined with the chemotherapy drug topotecan. BI 764532 may enhance the immune system's ability to fight cancer. This trial may suit those whose small cell lung cancer has progressed after previous treatments and who are eligible for chemotherapy. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not be enrolled in another drug trial or have been in one within the last 30 days, and you need to be off steroids and anti-epileptic drugs for at least 7 days if you have brain metastases.

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

In earlier studies, BI 764532 has shown potential in targeting cancer cells. It is designed to help the immune system fight cancer by attaching to specific markers on tumor cells. While this approach is promising, understanding its safety in humans remains incomplete. So far, some patients have tolerated it well, but reports of side effects are common with new treatments.

Topotecan, however, has been used for a longer time and is already approved by the FDA for treating small cell lung cancer that has returned after initial treatment. This approval provides a better understanding of its safety. Common side effects include low blood cell counts, nausea, and tiredness.

Both treatments are under study together to assess their effectiveness and safety as a combination. While BI 764532 is newer and less understood, topotecan offers a known safety baseline. Participants should be aware that the combination is still under research, so monitoring and care during the trial are crucial to manage any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI 764532 combined with topotecan for small cell lung cancer because it represents a novel approach to targeting the disease. Unlike traditional chemotherapy, which often affects both cancerous and healthy cells, BI 764532 is designed to specifically target cancer cells, potentially reducing side effects and improving efficacy. This treatment also explores different dosing strategies, including low, medium, and high doses of BI 764532, which may help fine-tune its effectiveness and tolerability. By offering a targeted mechanism and flexible dosing, this combination has the potential to enhance outcomes for patients with small cell lung cancer.

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

Research has shown that BI 764532 holds promise for treating small cell lung cancer (SCLC). This treatment aids the immune system in identifying and destroying cancer cells. Early studies suggest it is safe and effective at certain doses. Topotecan is already used for treating recurrent SCLC, with response rates between 2% and 38%, depending on the cancer's reaction to previous treatments. In this trial, participants will receive various combinations of BI 764532 and topotecan to explore their combined effectiveness in helping patients with advanced SCLC. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults with advanced small cell lung cancer who've had platinum-based chemo can join this trial. They must be eligible for topotecan, have a performance status showing they're mostly active (ECOG 0-1), and provide consent and a tumor sample. People under 18 or those not fit for topotecan cannot participate.

Inclusion Criteria

I am eligible to receive topotecan treatment.

My small cell lung cancer has worsened after platinum and PD-1/PD-L1 treatments.

I have a stored sample of my tumor tissue.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Confirmation

Participants receive varying doses of BI 764532 in combination with a single agent chemotherapy to determine the highest tolerable dose

8-12 weeks

Regular visits depending on response

Treatment Continuation

Participants continue to receive BI 764532 as long as they benefit and can tolerate the treatment

Indefinite, based on response

Regular visits for health checks and laboratory tests

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
• Topotecan

Trial Overview The trial is testing the highest tolerable dose of BI 764532, an immune system-boosting molecule, combined with topotecan in adults with extensive stage small cell lung cancer after previous treatments. The drugs are given via infusion or as oral tablets for ongoing treatment based on benefit and tolerance.

How Is the Trial Designed?

Group I: Part B: BI 764532 + topotecan Experimental Treatment 2 Interventions

Group II: Part A: BI 764532 medium dose + topotecan/single agent chemotherapy Experimental Treatment 3 Interventions

Group III: Part A: BI 764532 low dose + topotecan/single agent chemotherapy Experimental Treatment 3 Interventions

Group IV: Part A: BI 764532 high dose + topotecan/single agent chemotherapy Experimental Treatment 3 Interventions

BI 764532 is already approved in United States for the following indications:

Approved in United States as BI 764532 for:

• None approved; under investigation for extensive-stage small cell lung cancer (ES-SCLC) and extrapulmonary neuroendocrine carcinoma (epNEC)

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

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]

Cisplatin, while one of the most effective treatments for non-small cell lung cancer (NSCLC), shows only moderate effectiveness and limited impact on survival rates, highlighting the need for better therapies.

Topotecan, a topoisomerase I inhibitor, has shown modest activity against NSCLC in preclinical studies and early clinical trials, suggesting it may be a potential treatment option worth further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan in the treatment of non-small cell lung cancer. Perez-Soler, R.[2013]

Topotecan, a topoisomerase I inhibitor, shows promise as a treatment for non-small cell lung cancer (NSCLC) due to its manageable noncumulative hematologic toxicities and favorable tolerability compared to standard chemotherapy agents.

Combination regimens involving topotecan have demonstrated encouraging antitumor activity and may provide meaningful clinical benefits, particularly in palliative care for advanced NSCLC patients, making it a viable option for second-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the role of topotecan in the treatment of non-small cell lung cancer. Stewart, DJ.[2013]

Topotecan has demonstrated effectiveness in treating various cancers, including metastatic ovarian cancer and recurrent small cell lung cancer, with response rates of 20% in ovarian cancer compared to 13% for paclitaxel, and a notable median survival of 5.4 months in SCLC patients.

The drug is generally well-tolerated, with myelosuppression being the main side effect, but serious complications are rare, making it a manageable option for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan, an active new antineoplastic agent: review and current status. Carmichael, J., Ozols, RF.[2019]

Topotecan, a drug that targets topoisomerase I, has shown significant antitumor activity when combined with various chemotherapy agents like cisplatin and doxorubicin in both adult and pediatric patients with solid tumors.

The main side effect of these combination therapies is myelosuppression, particularly neutropenia, which limits the dosage; however, many early studies have reported major responses, indicating the potential effectiveness of these regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan in combination chemotherapy. Rowinsky, EK., Kaufmann, SH.[2017]

Topotecan is a promising topoisomerase I inhibitor that shows effectiveness in treating relapsed small-cell lung cancer (SCLC) and is being studied for first-line therapy in SCLC and non-small-cell lung cancer (NSCLC).

Current research is exploring the use of topotecan as a single agent and in combination therapies for various cancers, with a focus on developing a more convenient oral formulation and optimizing treatment regimens to improve patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future role of topotecan in the treatment of lung cancer. Schiller, JH.[2017]

The study found that the oral formulation of topotecan (Xinze(®)) has a good bioavailability of approximately 41.23% at a dose of 1.5 mg/m²/d and 36.00% at 1.9 mg/m²/d in Chinese patients with advanced cancers, indicating effective systemic exposure to the drug.

Pharmacokinetic analysis showed that the maximum plasma concentration of topotecan was reached within 1-2 hours after oral administration, with a consistent elimination half-life of about 4.2 hours, suggesting a reliable absorption and elimination profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral topotecan: Bioavailability, pharmacokinetics and impact of ABCG2 genotyping in Chinese patients with advanced cancers. Li, N., Song, Y., Du, P., et al.[2022]

Topotecan is an effective and tolerable treatment option for patients with recurrent small cell lung cancer (SCLC), showing antitumor activity in both chemosensitive and refractory cases, as confirmed by phase II and phase III clinical trials.

The predictable and manageable toxicity profile of topotecan makes it suitable for patients with poor prognosis, and alternative dosing regimens and an oral formulation may enhance its use in both first- and second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan in the treatment of recurrent small cell lung cancer: an update. Ardizzoni, A.[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. 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.

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. onclive.com onclive.com/view/bi-764532-yields-promising-safety-and-efficacy-results-in-dll3-sclc-and-neuroendocrine-carcinomas

BI 764532 Yields Promising Safety and Efficacy Results in ... The novel T-cell engager BI 764532 demonstrated a clinically acceptable safety profile and early efficacy when administered at doses of 90 μg/kg or greater.

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. boehringer-ingelheim.com boehringer-ingelheim.com/science-innovation/human-health-innovation/clinical-pipeline/obrixtamig-bi-764532-dll3-cd3-t-cell-engager-0

Obrixtamig (BI 764532): DLL3/CD3 T-cell engager T-cell engagers are targeted immunotherapeutics, which can directly reactivate T-cells, potentially resulting in the selective killing of tumor cells.