BI 764532 + Chemotherapy for Neuroendocrine Tumors

Recruiting at 30 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must be taking: Platinum-based chemotherapy

Disqualifiers: Merkel cell carcinoma, Medullary thyroid carcinoma, 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 36 months

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, BI 764532 (an experimental treatment), combined with chemotherapy for individuals with advanced neuroendocrine cancer, which affects hormone-producing cells. The goal is to determine the optimal dose that participants can tolerate and to assess the effectiveness of this combination. Participants will receive varying doses of BI 764532 intravenously, along with chemotherapy, to evaluate its potential to shrink cancer. The study seeks participants whose tumors have a specific marker called DLL3 and who have a type of neuroendocrine cancer that has spread or is difficult to treat. Regular doctor visits will monitor health, side effects, and changes in tumor size. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not need steroids or anti-convulsants for at least 7 days before starting the trial medication.

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

Research has shown that BI 764532, the treatment tested in this study, demonstrated promising safety results in earlier research. These studies involved patients with certain types of neuroendocrine cancers. The treatment was generally well-tolerated, meaning most patients handled it without serious side effects. Importantly, the highest dose tested did not cause excessive problems, suggesting the drug can be administered at higher levels safely.

In these earlier studies, any side effects were manageable. While some patients experienced side effects, they were not severe enough to stop the treatment. This is encouraging for those considering joining the trial, as it suggests the treatment has a good safety record based on the available data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI 764532 because it represents a novel approach for treating neuroendocrine tumors. Unlike traditional chemotherapy that broadly attacks cancer cells, BI 764532 targets specific pathways in the tumor cells, potentially leading to more effective and personalized treatment. The combination of BI 764532 with chemotherapy agents like carboplatin, cisplatin, and etoposide may enhance the efficacy of standard treatments, offering hope for better outcomes. This targeted approach could reduce side effects and improve the quality of life for patients compared to conventional options.

What evidence suggests that this trial's treatments could be effective for neuroendocrine tumors?

This trial will evaluate BI 764532 combined with chemotherapy for neuroendocrine tumors. Research has shown that BI 764532, when used with chemotherapy, may help treat tumors with the DLL3 marker. In some studies, patients with certain types of neuroendocrine cancers showed a 70% positive response rate to active doses of BI 764532. The treatment also caused side effects that were generally manageable, allowing most patients to tolerate it well. Although more research is needed, these early results suggest that BI 764532 could be a promising option for people with DLL3-positive neuroendocrine tumors. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

Adults with advanced neuroendocrine cancer (NEC) that tests positive for DLL3 can join. They must have a measurable tumor, expect to live at least 12 weeks, and not have had certain radiotherapies recently. The trial is open to those over 18 or the legal age in their country who can consent.

Inclusion Criteria

I have signed the consent form for this trial.

Minimum life expectancy of 12 weeks

I am fully active or can carry out light work.

Exclusion Criteria

I have not had extensive radiotherapy, including to the brain, within the last week.

My cancer has spread to the lining of my brain and spinal cord.

Previous treatment in this trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive different doses of BI 764532 in combination with platinum-based chemotherapy as infusions into a vein. Treatment can continue up to 3 years if beneficial and tolerated.

Up to 36 months

Regular visits for health monitoring and tumor size checks

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 study evaluates BI 764532 plus chemotherapy in two parts: finding the highest tolerable dose of BI 764532 (Part A), and assessing tolerance and effectiveness with different chemotherapies (Part B). Treatment involves infusions up to three years if beneficial.

How Is the Trial Designed?

Group I: Part B: BI 764532 + cisplatin + etoposide Experimental Treatment 3 Interventions

Group II: Part B: BI 764532 + carboplatin + etoposide Experimental Treatment 3 Interventions

Group III: Part A: BI 764532 medium dose + carboplatin + etoposide Experimental Treatment 3 Interventions

Group IV: Part A: BI 764532 low dose + carboplatin + etoposide Experimental Treatment 3 Interventions

Group V: Part A: BI 764532 high dose + carboplatin + etoposide 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

Chemotherapy for malignant neuroendocrine tumors, particularly those of pancreatic origin, can be effective, with up to 60% of patients responding positively to a combination of streptozocin and doxorubicin.

However, well-differentiated neuroendocrine tumors from the gastrointestinal tract show almost no response to chemotherapy, highlighting the need for tailored treatment approaches based on tumor type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine tumours of the gastrointestinal tract: Chemotherapy. Arnold, R., Rinke, A., Schmidt, Ch., et al.[2013]

Intestinal neuroendocrine tumors (NETs) are diverse and vary in treatment based on their location, with small intestinal NETs typically treated first with somatostatin analogs, and options like everolimus or interferon alpha available if progression occurs.

Rectal NETs can be effectively treated with somatostatin analogs and peptide receptor radionuclide therapy (PRRT), while more aggressive colonic NETs often require everolimus or cytotoxic agents, highlighting the importance of tumor characteristics in determining treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical Therapy of Gastrointestinal Neuroendocrine Tumors. Öberg, K.[2020]

Bortezomib, a proteasome inhibitor, shows short-term sensitizing effects when combined with DNA-damaging therapies like cisplatin and radiation, by impairing DNA repair mechanisms in well-differentiated gastroenteropancreatic neuroendocrine neoplasms.

Despite these promising short-term effects, the study found no significant long-term therapeutic advantage of combining bortezomib with peptide receptor radionuclide therapy (PRRT) due to high tumor heterogeneity observed in the in vivo mouse model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? - A preclinical assessment in vitro and in vivo. Briest, F., Koziolek, EJ., Albrecht, J., et al.[2021]

In a noninterventional trial involving patients with advanced neuroendocrine tumors (NETs), the combination of Everolimus and Octreotide LAR demonstrated a clinical benefit rate of 69%, indicating significant efficacy in managing the disease.

The treatment was well-tolerated, with most patients experiencing stable disease, and a small number continuing therapy for over 12 cycles, suggesting a favorable safety profile in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus plus octreotide long-acting repeatable in advanced neuroendocrine tumors in the routine tertiary cancer care setting: An Indian experience. Tippeswamy, R., Patil, S., Sateesh, CT., et al.[2016]

In a study of 78 patients with advanced neuroendocrine tumors (NETs), oxaliplatin-based chemotherapy demonstrated a disease control rate of 80%, with a median progression-free survival of 8 months and overall survival of 32 months, indicating its potential efficacy.

The treatment was generally well-tolerated, with manageable side effects primarily being neurological and gastrointestinal, suggesting that oxaliplatin-based regimens could be a viable option for patients with advanced NETs, particularly those with pancreatic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors. Spada, F., Antonuzzo, L., Marconcini, R., et al.[2018]

Citations

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

Phase I Dose-Escalation Results for the Delta-Like Ligand ... Across all doses, regimens, and tumor types, the overall response rate (ORR) was 23% (95% CI, 17.4% to 30.2%), the median duration of response ( ...

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. sciencedirect.com sciencedirect.com/science/article/pii/S155608642400933X

OA10.05 Phase I Trial of DLL3/CD3 IgG-Like T-Cell ... Conclusions. BI 764532 showed promising efficacy and safety in patients with LCNEC, with an ORR of 70% at active dose levels. Keywords.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02255-5/fulltext

670P Phase I trial of the delta-like ligand-3 (DLL3)/CD3 IgG ... Conclusions. BI 764532 showed clinically manageable tolerability and promising efficacy in SCLC, epNEC and LCNEC. SCLC ORR/DCR ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3004

Efficacy and safety of the DLL3/CD3 T-cell engager ... Obrixtamig (BI 764532) is a DLL3/CD3 IgG-like T-cell engager that targets DLL3-positive (DLL3+) tumors. NCT04429087 is an ongoing, Phase (Ph) I ...

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. endocrine-abstracts.org endocrine-abstracts.org/ea/0108/ea0108c12

Updated phase 1 data for the DLL3/CD3 IgG-like T-cell ... Conclusions: BI 764532 showed clinically manageable tolerability; MTD was not reached. Promising efficacy was observed in patients with epNEC. The study is ...

8. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/cancer/lung-cancer/our-goal-transforming-treatment-neuroendocrine-carcinomas

Our goal of transforming the treatment of neuroendocrine ... We are investigating BI 764532, an investigational DLL3 targeting IgG-like T-cell engager, for the treatment of people living with relapsed SCLC, LCNEC-L and ...