TUB-040 for Ovarian and Lung Cancers

(NAPISTAR1-01 Trial)

Recruiting at 10 trial locations

Overseen By Tubulis Clinical Trial Inquiries

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Tubulis GmbH

Must not be taking: Topoisomerase-I inhibitors

Disqualifiers: Pregnancy, CNS disease, ILD, others

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

Compensation: Varies

Number of Visits: 6

100 Participants Needed

Trial Summary

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 participate if you are currently on chemotherapy, radiotherapy, immunotherapy, or corticoid therapy. It's best to discuss your specific medications with the trial team.

What safety data exists for TUB-040 in humans?

The safety data for taxanes, a class of drugs that includes paclitaxel and docetaxel, shows that they can cause side effects like hypersensitivity (allergic reactions), leukopenia (low white blood cell count), neurotoxicity (nerve damage), and alopecia (hair loss). Premedication can reduce severe allergic reactions. In some studies, patients experienced significant neutropenia (low levels of a type of white blood cell) with certain dosing schedules. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this multicentric, open label trial (NAPISTAR 1-01) is to evaluate the safety/tolerability, pharmacokinetics and preliminary efficacy of TUB-040 and to find the best dose of TUB-040 in patients with ovarian cancer and Non Small Cell Lung Cancer. TUB-040 is an antibody-drug-conjugate which delivers a topoisomerase I inhibitor to tumor cells which overexpress the target NaPi2b. The study consists of two parts: In dose escalation, ovarian cancer patients and lung cancer patients receive increasing doses of TUB-040 until the maximal tolerated dose is found. In dose optimization, at least two doses are compared with each other to determine which dose is optimal for patients. TUB-040 is given IV every 3 weeks until the disease progresses or the patient has to stop due to side effects.

Research Team

Guenter Fingerle-Rowson, MD, PhD

Principal Investigator

Tubulis GmbH

Eligibility Criteria

This trial is for patients with ovarian cancer or recurrent/refractory adenocarcinoma non-small cell lung cancer. Participants must have a tumor that overexpresses NaPi2b and can receive intravenous treatments every 3 weeks. Specific eligibility details are not provided, but typically include factors like age, health status, and prior treatments.

Inclusion Criteria

My organs are working well.

Have a life expectancy of more than 12 weeks for disease-related mortality, as evaluated by the INV

I am willing to have a detailed lung scan and lung function tests.

Exclusion Criteria

I am allergic to exatecan or ingredients in TUB-040.

I have had nephrotic syndrome in the past.

I have spinal cord compression or active brain disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Ovarian cancer and lung cancer patients receive increasing doses of TUB-040 until the maximal tolerated dose is found

Variable, until maximal tolerated dose is found

Every 3 weeks

Dose Optimization

At least two doses are compared to determine the optimal dose for patients

Variable, based on dose comparison

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TUB-040

Trial Overview The study tests TUB-040, an antibody-drug-conjugate targeting NaPi2b to deliver a topoisomerase I inhibitor directly to cancer cells. It's given IV every 3 weeks in two phases: finding the highest dose patients can tolerate (dose escalation) and then determining the best dose (dose optimization).

Participant Groups

Group I: Platinum resistant ovarian cancer Experimental Treatment 1 Intervention

Group II: Non small cell lung cancer-adenocarcinoma Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Tubulis GmbH

Lead Sponsor

Trials

2

Recruited

230+

Findings from Research

Paclitaxel and docetaxel, two taxanes used in treating ovarian cancer, have shown clinical activity, with response rates of 20-48% for paclitaxel and 33-35% for docetaxel in previously treated patients, indicating their efficacy even in platinum-resistant tumors.

Premedication with dexamethasone, diphenhydramine, and cimetidine can significantly reduce the risk of severe allergic reactions to taxanes to less than 3%, highlighting a safety measure for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Options for primary chemotherapy of epithelial ovarian cancer: taxanes. Trimble, EL., Arbuck, SG., McGuire, WP.[2018]

In a phase II trial involving 27 patients with recurrent uterine or epithelial ovarian cancers, the combination of weekly topotecan and docetaxel showed a 25% overall response rate, indicating its potential efficacy in this heavily treated population.

The treatment was generally well tolerated, with manageable toxicities, and resulted in a median overall survival of 18.5 months, suggesting that it may provide clinical benefit, especially for patients with platinum-resistant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine and ovarian cancers. Gupta, D., Owers, RL., Kim, M., et al.[2021]

The maximum tolerated dose (MTD) for the combination of intravenous paclitaxel and intraperitoneal carboplatin was determined to be carboplatin AUC 6, with 35% of patients experiencing dose-limiting toxicities (DLTs) during the first four treatment cycles.

The treatment regimen, which included paclitaxel at 175 mg/m² IV and carboplatin AUC 6 IP, showed a significant incidence of DLTs, prompting a dose de-escalation to improve safety, indicating the need for careful monitoring and adjustment in treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gould, N., Sill, MW., Mannel, RS., et al.[2021]

The maximum tolerated dose (MTD) for the combination of intravenous docetaxel, intraperitoneal carboplatin, and intraperitoneal paclitaxel was established as docetaxel 75 mg/m², carboplatin AUC 6, and paclitaxel 60 mg/m², but this regimen was not feasible over four treatment cycles due to significant bone marrow toxicity.

Fifteen out of 40 evaluable patients experienced dose-limiting toxicities, including severe neutropenia and infections, indicating that while the treatment shows potential, adjustments such as reducing carboplatin to AUC 5 may be necessary for safer administration in women with advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study with an expanded cohort to assess feasibility of intravenous docetaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with previously untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gould, N., Sill, MW., Mannel, RS., et al.[2021]

Topotecan, administered to 141 patients with small-cell lung cancer and recurrent ovarian cancer, showed an overall response rate of 33.8%, indicating it is an effective treatment option, especially for patients who have not undergone prior chemotherapy.

The main side effect observed was myelosuppression, which is a decrease in bone marrow activity leading to reduced blood cell production, while other non-hematopoietic toxicities were mild and manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of topotecan in the treatment of small cell lung cancer and recurrent ovarian cancer]. Feng, F., He, X., Shi, Y.[2013]

References

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

Options for primary chemotherapy of epithelial ovarian cancer: taxanes. [2018]

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

A phase II study of weekly topotecan and docetaxel in heavily treated patients with recurrent uterine and ovarian cancers. [2021]

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

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study. [2021]

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

A phase I study with an expanded cohort to assess feasibility of intravenous docetaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with previously untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study. [2021]

5. China pubmed.ncbi.nlm.nih.gov

[Clinical study of topotecan in the treatment of small cell lung cancer and recurrent ovarian cancer]. [2013]