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

NCT06303505 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: NAPISTAR 1-012024-511074-80
• Study Type: interventional
• Target: 250
• Locations: 7 countries
• Sites: 15

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer; Ovarian Cancer

Keywords

TUB-040; ADC; PROC

Outcome Measures

Primary Outcomes (1)

• Determination of MTD

  The highest dose is defined at which no more than 1 of 3 patients have had a Dose Limiting Toxicity (DLT) according to NCI CTCAE V5.0 criteria

  From enrollment until 30 days after last study drug

Secondary Outcomes (7)

• Maximum plasma/serum concentration (Cmax)

  From enrollment until 30 days after last study drug

• Through plasma/serum concentration (Cmin)

  From enrollment until 30 days after last study drug

• The time taken to reach the maximum concentration (Tmax)

  From enrollment until 30 days after last study drug

• Area Under Curve (AUC)

  From enrollment until 30 days after last study drug

• Half life (T1/2)

  From enrollment until 30 days after last study drug

Study Arms (3)

Platinum resistant ovarian cancer

EXPERIMENTAL

Drug: TUB-040

Non small cell lung cancer-adenocarcinoma

EXPERIMENTAL

Drug: TUB-040

Platinum resistant ovarian cancer in combination with Bevacizumab

EXPERIMENTAL

Drug: TUB-040

Interventions

TUB-040 DRUG

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

Non small cell lung cancer-adenocarcinoma; Platinum resistant ovarian cancer; Platinum resistant ovarian cancer in combination with Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or non-pregnant, non-breastfeeding female, age 18 years or older at the date of consent.
• Disease not amenable to curative intent treatment.
• Patients 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.
• Radiologically measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, that includes at least 1 lesion not previously irradiated.
• Eastern Cooperative Oncology Group (ECOG) 0-1.
• Have a life expectancy of more than 12 weeks for disease-related mortality, as evaluated by the INV.
• Patients must be willing to sign an archival tissue release form for research purposes and determination of biomarker (eg NaPi2b) expression.
• Patients must be willing to undergo a non-contrast high resolution computed tomography (HRCT) of the thorax scan and pulmonary function testing (PFT) at screening.
• Adequate organ function
• 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).
• Patients 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 patients assigned female at birth. Abstinence is acceptable only as true abstinence when this is in line with the preferred and usual lifestyle of the patient for the duration of the study treatment and the above-referred period after the end of the exposure. Periodic abstinence (e.g., calendar ovulation, symptothermal, post-ovulation methods), the rhythm method, and the withdrawal method are not acceptable methods of contraception.
• In the opinion of the investigator, the patient must be able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations.
• The patient must not have a history of non-compliance with medical regimens or be considered potentially unreliable and/or uncooperative.
• The patient must be willing to sign and date the informed consent form (ICF)

You may not qualify if:

• The patient is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.
• History of hypersensitivity to exatecan or excipients of the TUB-040 formulation, including ADCs with deruxtecan, exatecan or camptothecan as a payload.
• Disease that is refractory to topoisomerase-I inhibitors, defined as progression during or within 6 months of the last infusion.
• Patients 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.
• Patients with spinal cord compression or active central nervous system disease.
• Major surgery within 21 days prior to signing the ICF, unless the patient is recovered at that time.
• Has a history of non-infectious ILD/pneumonitis/radiation pneumonitis that required steroids or has current ILD/pneumonitis.
• Has an oxygen saturation of \<93% on room air at rest.
• Has a forced vital capacity of \<60% and diffusing capacity of the lung for carbon monoxide \<70%.
• Has a QTcF \>470 ms
• History of nephrotic syndrome
• Active corneal disease, or history of corneal disease within 12 months prior to enrollment.
• Active, uncontrolled impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic, or hematopoietic systems which, in the opinion of the investigator, would predispose the patient to the development of complications from the administration of protocol therapy.
• 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.
• 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).

Sponsors & Collaborators

• Tubulis GmbH: lead

Study Sites (15)

The University of Alabama

Birmingham, Alabama, 35294, United States

RECRUITING

Mount Sinai

New York, New York, 10011, United States

RECRUITING

Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210#, United States

RECRUITING

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Next Oncology Dallas

Irving, Texas, 75039, United States

RECRUITING

Next Oncology Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

RECRUITING

University Hospital Cologne Department of Internal Medicine I

Cologne, 50937, Germany

RECRUITING

Arensia Exploratory Medicine

Cluj-Napoca, Romania

RECRUITING

Clínica universidad de Navarra

Madrid, 28027, Spain

RECRUITING

NEXT Oncology Madrid

Madrid, 28223, Spain

RECRUITING

Arensia Exploratory Medicine

Kyiv, Ukraine

RECRUITING

Guy's Hospital

London, SE1 9RT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yariv Houvras, MD, PhD

  Tubulis GmbH

  STUDY DIRECTOR

Central Study Contacts

Tubulis Clinical Trial Inquiries

CONTACT

+ 49 175 800 5594; ct-inquiries@tubulis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2024
• First Posted: March 12, 2024
• Study Start: June 12, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); BE (1); RO (1); DE (2); ES (2); GB (1); UA (1)