BI 764532 + Topotecan for Small Cell Lung Cancer

Recruiting at 15 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

Trial Summary

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.

What data supports the effectiveness of the drug combination BI 764532 and Topotecan for treating small cell lung cancer?

Topotecan has shown effectiveness in treating small cell lung cancer (SCLC), especially in patients with recurrent SCLC, providing symptom relief and manageable side effects. It has been used successfully in combination with other drugs for SCLC, suggesting potential benefits when combined with BI 764532. ^{1 2 3 4 5}

Is the combination of BI 764532 and Topotecan safe for humans?

Topotecan, also known as Hycamtin, has been studied in various cancer treatments and is generally well-tolerated by most patients. The main side effect is myelosuppression (a decrease in bone marrow activity), particularly neutropenia (low levels of a type of white blood cell), but serious side effects are uncommon and manageable. ^{1 3 5 6 7}

What makes the drug BI 764532 + Topotecan unique for treating small cell lung cancer?

The combination of BI 764532 and Topotecan is unique because it involves a novel drug, BI 764532, paired with Topotecan, a topoisomerase I inhibitor known for its activity in small cell lung cancer. This combination may offer a new approach by potentially enhancing the effectiveness of Topotecan, which is already used in relapsed cases, and exploring new treatment possibilities for this aggressive cancer. ^{1 2 3 5 8}

What is the purpose of this trial?

This study is open to adults with extensive stage small cell lung cancer. The study is in people with advanced cancer that had previously received platinum-based chemotherapy and are eligible to receive a single agent chemotherapy treatment. The purpose of this study is to find the highest dose of BI 764532 that people can tolerate when taken together with a single agent chemotherapy. BI 764532 is an antibody-like molecule that may help the immune system fight cancer. Participants may continue to take BI 764532 as long as they benefit from treatment and can tolerate it. During this time, participants visit the study site regularly. The visits also depend on the response to the treatment. At the study visits, the doctors check the health of the participants, take necessary laboratory tests, and note any health problems that could have been caused by the study treatment.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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, 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 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]

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 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]

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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Topotecan in combination chemotherapy. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Topotecan in the treatment of recurrent small cell lung cancer: an update. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. France pubmed.ncbi.nlm.nih.gov

Oral topotecan: Bioavailability, pharmacokinetics and impact of ABCG2 genotyping in Chinese patients with advanced cancers. [2022]

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

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

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

Topotecan in the treatment of non-small cell lung cancer. [2013]