TUB-040 for Ovarian and Lung Cancers

(NAPISTAR1-01 Trial)

Recruiting at 13 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TUB-040 for individuals with ovarian cancer and non-small cell lung cancer. TUB-040 delivers a cancer-fighting drug directly to tumor cells with a specific marker. The trial seeks to determine the safest and most effective dose. Individuals who have exhausted all standard treatments without success and have a measurable tumor on a scan may be suitable candidates for this trial. Participants will receive the treatment every three weeks until their condition worsens or they experience side effects. As a Phase 1 trial, this research focuses on understanding how TUB-040 works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that TUB-040 is likely to be safe for humans?

Research has shown that TUB-040 is generally safe for patients with ovarian cancer. Previous studies found that most patients tolerated the treatment well, with few major side effects, indicating its relative safety.

For lung cancer, evidence also suggests that TUB-040 is well-tolerated. As an antibody-drug conjugate, it delivers medicine directly to cancer cells. This targeted approach may help reduce side effects by focusing on tumor cells.

Both sets of findings suggest TUB-040 holds promise in terms of safety for treating these cancers. However, individual experiences may vary. Discuss potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian and lung cancers?

Researchers are excited about TUB-040 because it offers a novel approach for treating platinum-resistant ovarian cancer and non-small cell lung cancer. Unlike standard chemotherapy options, TUB-040 is designed to target cancer cells more precisely, potentially reducing damage to healthy cells and minimizing side effects. This new treatment leverages a unique mechanism of action that interrupts specific cancer cell pathways, which could lead to more effective outcomes. By focusing on these distinct cancer pathways, TUB-040 holds promise for patients who have not responded well to existing therapies.

What evidence suggests that TUB-040 might be an effective treatment for ovarian and lung cancers?

This trial will evaluate TUB-040 for both platinum-resistant ovarian cancer and non-small cell lung cancer (NSCLC) adenocarcinoma. Research has shown that TUB-040 yields promising results for treating platinum-resistant ovarian cancer. In earlier studies, over 50% of patients experienced a positive response, with significant tumor shrinkage. The treatment was well-tolerated, with no severe side effects reported.

For NSCLC adenocarcinoma, TUB-040 targets a protein called NaPi2b, commonly found in these cancer cells. This approach aims to deliver the drug directly to the cancer cells, potentially increasing effectiveness and reducing harm to healthy cells. Early results suggest it could be a viable option for patients with limited treatment choices. ^{1 2 3 5 6}

Who Is on the Research Team?

Guenter Fingerle-Rowson, MD, PhD

Principal Investigator

Tubulis GmbH

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1556086425020945

An International Phase I/II Trial of the Novel ADC TUB-040 ... TUB-040 offers a novel therapeutic strategy for advanced NSCLC adenocarcinoma patients with limited treatment options. The high prevalence of NaPi2b expression ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06303505

NCT06303505 | FiH Study to Investigate Safety, PK and ... The purpose of this multicentric, open label trial (NAPISTAR 1-01) is to evaluate the safety/tolerability, pharmacokinetics and preliminary efficacy of TUB-040.

3. tubulis.com tubulis.com/news/tubulis-presents-first-clinical-data-from-phase-i-iia-trial-for-tub-040-in-platinum-resistant-ovarian-cancer-proc-at-esmo-2025/

First positive data TUB-040 in ovarian cancer The ongoing NAPISTAR 1-01 study (NCT06303505) is evaluating TUB-040 in PROC-HGSOC and in adenocarcinoma non-small cell lung cancer (NSCLC).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12580765/

TUB-040, a Homogeneous and Hydrophilic NaPi2b ... Consistent with these data, our IHC results, using a mouse chimera of the TUB-040 NaPi2b mAb, showed high expression of NaPi2b, especially in nonmucinous, high- ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS8660

NAPISTAR 1-01: An international phase I/II trial of the novel ... NAPISTAR 1-01 (NCT06303505) is an open-label, multicenter, Phase I/IIa study investigating TUB-040 in platinum-resistant ovarian cancer (PROC) and advanced ...

6. aacrjournals.org aacrjournals.org/mct/article/doi/10.1158/1535-7163.MCT-25-0254/763661/TUB-040-a-Homogeneous-and-Hydrophilic-NaPi2b

TUB-040, a Homogeneous and Hydrophilic NaPi2b-Targeting ... TUB-040, a Homogeneous and Hydrophilic NaPi2b-Targeting ADC with Stably Linked Exatecan, Exhibits Long-lasting Antitumor Activity and a Well-Tolerated Safety ...