FiH Study to Investigate Safety, PK and Efficacy of the NaPi2b ADC TUB-040 in Patients With PROC or r/r Adenocarcinoma NSCLC (NAPISTAR1-01)

September 10, 2026 updated by: Tubulis GmbH

A Multicenter, First-in-human Dose Escalation and Optimization Phase I/IIa Study to Investigate Safety, Tolerability, PK, and Efficacy of the NaPi2b ADC TUB-040 in Patients With Platinum-resistant High-grade Ovarian Cancer (PROC) or r/r Adenocarcinoma Non-small Cell Lung Cancer (NSCLC)

The purpose of this multicenter, 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 participants 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 three parts: In dose escalation, ovarian cancer participants and lung cancer participants 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 participants. In dose expansion, a single dose will be used in a larger number of participants.

TUB-040 is given IV every 3 weeks until the disease progresses or the participants has to stop due to side effects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

250

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
    • Belgium
      • Leuven, Belgium, Belgium, 3000
  • Germany
      • Berlin, Germany, 10117
        • Recruiting
        • Charité Universitätsmedizin Berlin
        • Contact:
      • Cologne, Germany, 50937
        • Recruiting
        • University Hospital Cologne Department of Internal Medicine I
        • Contact:
  • Puerto Rico
      • San Juan, Puerto Rico, 00927
        • Not yet recruiting
        • Puerto Rico Cancer Clinical Trials
  • Romania
      • Cluj-Napoca, Romania
  • Spain
      • Madrid, Spain, 28027
        • Recruiting
        • Clinica Universidad de Navarra
        • Contact:
      • Madrid, Spain, 28223
  • Ukraine
      • Kyiv, Ukraine
        • Active, not recruiting
        • ARENSIA Exploratory Medicine
  • United Kingdom
      • London, United Kingdom, SE1 9RT
        • Active, not recruiting
        • Guy's Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Not yet recruiting
        • Yale Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Not yet recruiting
        • Emory University
    • Kentucky
      • Louisville, Kentucky, United States, 40217
        • Not yet recruiting
        • Norton Cancer Institute Research
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Not yet recruiting
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02111
        • Not yet recruiting
        • Tufts
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
    • New York
      • New York, New York, United States, 10011
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • Christ Hospital
        • Contact:
      • Columbus, Ohio, United States, 43210#
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • OU Health Stephenson Cancer Center
        • Contact:
    • Oregon
      • Medford, Oregon, United States, 97504
        • Not yet recruiting
        • Asante / Heimann Cancer Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • Not yet recruiting
        • Allegheny Singer
    • South Carolina
      • Spartanburg, South Carolina, United States, 29303
        • Not yet recruiting
        • Spartanburg Regional
    • Texas
      • Fort Worth, Texas, United States, 76104
      • Irving, Texas, United States, 75039
    • Utah
      • West Valley City, Utah, United States, 84119
        • Recruiting
        • START Mountain Region
        • Contact:
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • NEXT Oncology Virginia
        • Contact:
      • Fairfax, Virginia, United States, 22031
        • Not yet recruiting
        • Inova Schar Cancer Institute
    • Washington
      • Spokane, Washington, United States, 99204
        • Not yet recruiting
        • Providence Sacred Heart Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria (for all phases)

  1. Male or non-pregnant, non-breastfeeding female, age 18 years or older at the date of consent.
  2. Disease not amenable to curative intent treatment.
  3. Participants have exhausted the standard of care treatment (SoC) with expected survival benefit and are not denied SoC with expected survival benefit by participating in the trial.
  4. Participants with previous systemic topoisomerase I inhibitor treatment (e.g., Topotecan) are allowed in the study.
  5. Radiologically measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the INV.
  6. Eastern Cooperative Oncology Group (ECOG) 0-1.
  7. Have a life expectancy of more than 12 weeks for disease-related mortality, as evaluated by the INV.
  8. Participants must be willing to sign an archival tissue release form for research purposes and determination of biomarker expression.
  9. Participants must be willing to undergo a non-contrast high resolution computed tomography (HRCT) of the thorax scan and pulmonary function testing (PFT) at screening.
  10. Adequate organ function
  11. Resolution of all acute toxic effects of prior therapy or surgical procedures to ≤grade 1 (except alopecia, hyperpigmentation, or discoloration (incl. vitiligo) of the skin and nails, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on ≤10 mg daily prednisone [or equivalent], chronic grade 2 peripheral sensory neuropathy after prior taxane therapy or anticancer treatment such as but not limited to IOs).
  12. Participants of childbearing potential (FCBP) who are sexually active with a non-sterilized partner must use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions until the end of exposure, plus 5 half-lives and 6 months add-on in the case of participants assigned female at birth.
  13. In the opinion of the investigator, the participant must be able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations.
  14. The participant must not have a history of non-compliance with medical regimens or be considered potentially unreliable and/or uncooperative.
  15. The participant must be willing to sign and date the informed consent form (ICF)

Key Exclusion Criteria (for all phases)

  1. The participant is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.
  2. History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.
  3. Participants are not allowed to participate in interventional clinical studies either concurrently or within the previous 28 days or within 5 half-lives of any investigational pharmacologic agents or imaging materials, including dyes, investigational surgical techniques, or devices.
  4. Participants with spinal cord compression or active central nervous system disease, and/or carcinomatous meningitis.
  5. Prior radiotherapy <2 weeks from trial inclusion.
  6. Major surgery within 21 days prior to signing the ICF, unless the participant is recovered at that time.
  7. Has a history of non-infectious ILD/pneumonitis/radiation pneumonitis that required steroids or has current ILD/pneumonitis.
  8. Has an oxygen saturation of <93% on room air at rest.
  9. Has a QTcF >470 ms
  10. History of nephrotic syndrome
  11. Active corneal disease, or history of corneal disease within 12 months prior to enrollment.
  12. Active, uncontrolled or severe impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic, or hematopoietic systems which, in the opinion of the investigator, would predispose the participant to the development of complications from the administration of protocol therapy.
  13. History of another malignancy with ongoing treatment or not yet free from disease for 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
  14. Documented other concurrent non-malignant comorbidities such as unstable or uncontrolled pectoral angina, myocardial infarction during the last 6 months, valvular heart disease that requires treatment, acute myocarditis, or congestive heart failure (CHF) (New York Heart Association III or IV).
  15. Any anti-tumor chemotherapy, systemic anti-cancer therapy, radiotherapy (except for local radiation therapy of lesions that may cause imminent complications), hormonal therapy, immunotherapy, or corticoid therapy.
  16. Concurrent use of strong inhibitors or strong inducers of CYP3A4
  17. Live vaccines within 30 days prior to study entry.

  18. Participants with acute or chronic infections such as:

    1. Participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have an undetectable HBV viral load prior to randomization.
    2. Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening.
    3. HIV infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease
    4. Any other known unresolved and active bacterial, viral, fungal, mycobacterial, or other infection at screening.
    5. History of severe and recurrent infections per INV judgment.
    6. History of progressive multifocal leukoencephalopathy

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Platinum resistant ovarian cancer
Drug: TUB-040
A complete treatment cycle is defined as 21 calendar days. TUB-040 will be administered as an intravenous (IV) solution on day 1 of each treatment cycle
Experimental: Non small cell lung cancer-adenocarcinoma
Drug: TUB-040
A complete treatment cycle is defined as 21 calendar days. TUB-040 will be administered as an intravenous (IV) solution on day 1 of each treatment cycle
Experimental: Platinum resistant ovarian cancer in combination with Bevacizumab
Drug: TUB-040
A complete treatment cycle is defined as 21 calendar days. TUB-040 will be administered as an intravenous (IV) solution on day 1 of each treatment cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs)[
Time Frame: First dose up to 21 days
First dose up to 21 days
Phase 1 and 2a: Percentage of Participants Experiencing Treatment-Emergent Adverse Event (TEAEs)
Time Frame: First dose date up to 30 days post last dose (Up to 3 years)
First dose date up to 30 days post last dose (Up to 3 years)
Phase 2a & 2b: Overall Response Rate (ORR) by Blinded Independent Central Review (BICR)
Time Frame: Up to 3 years
ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR), as assessed by BICR.
Up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 2a & 2b: Duration of Response (DOR) by BICR
Time Frame: Up to 3 years
DOR is defined as the interval from the first documentation of CR or PR until the date of first documented disease progression or death, whichever comes first, as assessed by BICR.
Up to 3 years
Phase 1, 2a & 2b: ORR by INV
Time Frame: Up to 3 years
ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR), as assessed by Investigator (INV).
Up to 3 years
Phase 1, 2a & 2b: DOR by INV
Time Frame: Up to 3 years
DOR is defined as the interval from the first documentation of CR or PR until the date of first documented disease progression or death, whichever comes first, as assessed by INV.
Up to 3 years
Phase 1, 2a & 2b: Progression-Free Survival (PFS) by INV
Time Frame: Up to 3 years
PRS is defined as the time from first dose date until disease progression or death from any cause, whichever comes first, as assessed by INV.
Up to 3 years
Phase 1, 2a & 2b: Disease Control Rate (DCR) by INV
Time Frame: Up to 3 years
DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease, as assessed by INV.
Up to 3 years
Phase 2a & 2b: Progression-Free Survival (PFS) by BICR
Time Frame: Up to 3 years
PRS is defined as the time from first dose date until disease progression or death from any cause, whichever comes first, as assessed by BICR.
Up to 3 years
Phase 2a & 2b: Disease Control Rate (DCR) by BICR
Time Frame: Up to 3 years
DCR is defined as the percentage of participants with a confirmed CR, PR, or stable disease, as assessed by BICR.
Up to 3 years
Phase 1, 2a & 2b: Percentage of Participants Experiencing Grade ≥3 Lab Abnormalities
Time Frame: First dose date up to last dose date plus 30 days
First dose date up to last dose date plus 30 days
Phase 1: Percentage of Participants Experiencing Serious Adverse Events (SAEs)
Time Frame: First dose date up to 30 days post last dose (Up to 3 years)
First dose date up to 30 days post last dose (Up to 3 years)
Phase 1 & 2a: Pharmacokinetic (PK) Parameter of TUB-040, total mAb, and Free Exatecan: Cmax
Time Frame: Up to 3 years
Cmax is defined as the maximum observed drug concentration.
Up to 3 years
Phase 1 & 2a: PK Parameter of TUB-040, Total mAb, and Free Exatecan: Cmin
Time Frame: Up to 3 years
The concentration of TUB-040 (conjugated ADC), total mAb, and free payload (Cmin will be derived).
Up to 3 years
Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Tmax
Time Frame: Up to 3 years
Tmax is defined as the time (observed time point) of Cmax.
Up to 3 years
Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Area Under Curve (AUC)
Time Frame: Up to 3 years
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Up to 3 years
Phase 1 & 2a: PK Parameter TUB-040, Total mAb, and Free Exatecan: Half life (T1/2)
Time Frame: Up to 3 years
T1/2 is defined as the terminal elimination half-life at steady state.
Up to 3 years
Phase 1, 2a & 2b: Percentage of Participants Developing anti-TUB-040 antibodies and semiquantitative titer assessments
Time Frame: From enrollment until 30 days after last study drug
From enrollment until 30 days after last study drug
Phase 2a & 2b: Overall Survival (OS)
Time Frame: Up to 3 years
OS is defined as the length of time from first dose until the date of death from any cause.
Up to 3 years
Phase 2a & 2b: CA-125 response according to Gynecological Cancer InterGroup (GCIG)
Time Frame: Up to 3 years
Up to 3 years
Phase 2a & 2b: Percentage of Participants Experiencing TEAEs
Time Frame: First dose date up to 30 days post last dose date (Up to 3 years)
First dose date up to 30 days post last dose date (Up to 3 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tubulis GmbH

Investigators

  • Study Director: Yariv Houvras, MD, PhD, Tubulis GmbH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 12, 2024

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

February 6, 2024

First Submitted That Met QC Criteria

March 6, 2024

First Posted (Actual)

March 12, 2024

Study Record Updates

Last Update Posted (Actual)

September 14, 2026

Last Update Submitted That Met QC Criteria

September 10, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NAPISTAR 1-01
  • 2024-511074-80 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

we first want to evaluate the ICMJE Guidelines

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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