Study of TUB-040 in Patients With Recurrent or Progressive Uterine Cancer After Chemotherapy and Immune Therapy (NAPISTAR 1-03)

A Multicenter Phase 1/2 Study to Investigate Safety, Tolerability, Pharmacokinetics, and Efficacy of the NaPi2B Antibody-Drug Conjugate TUB-040 in Patients With Recurrent or Progressive Uterine Endometrial Cancer After Platinum-Based Chemotherapy and Immune Checkpoint Inhibitor Therapy

The goal of this clinical study is to learn more about the study drug TUB-040, safety, tolerability, pharmacokinetics (PK), and effectiveness in treating patients with recurrent or progressive uterine endometrial cancer after platinum-based chemotherapy and immune checkpoint inhibitor therapy.

The primary objectives of Phase 1 of this study are to determine the safety and tolerability of TUB-040 and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D).

The primary objective of Phase 2 of this study is to evaluate the efficacy of TUB-040 monotherapy at the RP2D in endometrial cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Uterine Endometrial Cancer
• Intervention / Treatment: Drug: TUB-040 - Dose escalation; Drug: TUB-040 - RP2D

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tubulis Clinical Trial Inquiries; Phone Number: +49 175 800 5594; Email: ct-inquiries@tubulis.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • START Los Angeles
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • START New Jersey
  • New York
    • Lake Success, New York, United States, 11042
      • START New York-Long Island
  • Utah
    • West Valley City, Utah, United States, 84119
      • START Mountain Region, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed advanced recurrent or progressive serous or endometroid endometrial cancer.

   Note: Mixed histologies are allowed if the dominant subtype is serous or endometroid.

2. Pathological report with results of institutional MMR and/or MSI testing.

3. Received at least 1 but no more than 3 prior lines of anticancer therapy:

   a. Must have received at least 1 line of platinum-based therapy and 1 line of programmed death ligand-1 (PD-L1) or programmed death-1 (PD-1) inhibitor therapy (separately or in combination) Note: Induction plus maintenance is considered as 1 line of therapy. Hormonal therapy without chemotherapy will not be considered a separate line of therapy

   For dose escalation cohorts only:

   The requirement for prior treatment with a PD-1 or PD-L1 inhibitor is waived for patients enrolled in countries where treatment with these agents does not have regulatory approval for first line treatment after discussion with and approval from the Sponsor's medical monitor.

4. Radiographic progression on or after the most recent line of anticancer therapy.
5. Female aged ≥ 18 years at the time of consent.
6. Disease not amenable to curative intent treatment.
7. Radiologically measurable disease by RECIST v1.1, which can include a lesion in an irradiated field that showed progression by RECIST v1.1 after irradiation.
8. ECOG performance status of 0 or 1.
9. Life expectancy > 12 weeks for disease-related mortality as evaluated by the INV.
10. Willing to sign an archival tissue release form for research purposes and determination of biomarker (eg, NaPi2b) expression. An adequate tumor tissue sample, either a formalin-fixed, paraffin-embedded (FFPE) tissue block or a minimum of 6 freshly cut, unstained sections of the most recently available tumor sample, is mandatory for biomarker assessment by the central pathology laboratory. If no archival specimens are available, a newly acquired biopsy specimen must be provided
11. Willing to undergo a noncontrast high-resolution computed tomography (HRCT) scan of the thorax and pulmonary function testing at screening.

12. Adequate organ function as defined by all of the following criteria (parameters must be met without growth factor or transfusion support within 4 weeks prior to enrollment):

    1. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase and alanine aminotransferase (ALT)/serum glutamic pyruvate transaminase ≤ 3.0 × the upper limit of normal (ULN)
    2. Total serum bilirubin ≤ 1.5 × ULN (CTCAE Grade ≤ 1) unless secondary to Gilbert's syndrome. Patients with Gilbert's syndrome may be included if their unconjugated bilirubin is ≤ 3 × ULN.
    3. Estimated glomerular filtration rate (eGFR) > 50 mL/min calculated using the Chronic Kidney Disease Epidemiology Collaboration formula (Appendix B)
    4. Alkaline phosphatase (ALP) < 2.5 × ULN, except if there is an alternative explanation for ALP elevation other than hepatic failure, such as the presence of bone metastasis
    5. Hemoglobin ≥ 9.0 g/dL
    6. Absolute neutrophil count ≥ 1500/mm3
    7. Platelet count ≥ 100,000/mm3
    8. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN in the absence of anticoagulation therapy. If patients are on anticoagulation therapy, INR should be within the therapeutic range for the medical indication
13. Resolution of all AEs from prior therapy or surgical procedures to Grade ≤ 1 or to baseline (exceptions included alopecia, hyperpigmentation or discoloration of the skin and nails [including vitiligo], stable immune-related toxicity such as hypothyroidism for patients on hormone replacement or corticosteroid treatment with prednisone, or equivalent, of ≤ 10 mg daily, and Grade 2 peripheral sensory neuropathy after prior treatment with taxane or other anticancer therapy).
14. Women of childbearing potential (WOCP) must have a negative serum pregnancy test during screening and be neither breastfeeding or intending to become pregnant during study participation. A female will be considered to be of childbearing potential following menarche unless they have undergone permanent sterilization (ie, hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or are postmenopausal. Postmenopausal is defined as at least 12 months without menses with no other medical reason (eg, chemical menopause due to anticancer treatment).
15. For WOCP, agreement must be provided to use a medically approved, highly effective contraceptive method from the time of screening throughout the study and for 6 months after the last administration of study treatment.
16. Ability to understand, give written informed consent, comply with all study-related procedures, medication use, and assessments.
17. No history of noncompliance with medical regimens or considered, in the opinion of the INV, to be potentially unreliable and/or uncooperative.
18. Willing to sign and date the ICF

Exclusion Criteria:

1. Unresolved bowel obstruction, including radiographic findings consistent with bowel obstruction plus clinical signs and symptoms of obstruction such as nausea and/or vomiting.
2. Prior thoracocentesis for therapeutic drainage of malignant effusion within 4 weeks prior to initiation of study treatment.
3. Paracentesis for therapeutic drainage of malignant effusion within 4 weeks prior to initiation of study treatment.
4. Receiving total parenteral nutrition.
5. Serum albumin < 2.5 g/dL (patients should not receive IV albumin within 4 weeks prior to testing).
6. Known active central nervous system metastases and/or carcinomatous meningitis. Note: Previously treated brain metastases allowed if follow-up brain imaging after CNS directed therapy shows no evidence of progression, and they have been off steroids for > 4 weeks prior to first dose.
7. Pregnant, lactating, or breastfeeding.
8. History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.
9. Prior treatment with an ADC-containing Topo-1 inhibitor payload. ADCs with other payloads are allowed (eg, monomethyl auristatin E, monomethyl auristatin F).
10. Discontinuation of the most recent systemic anticancer therapy due to hematologic toxicity.
11. Participation in any interventional clinical studies either concurrently or within 28 days or 5 half-lives (whichever is shorter) prior to enrollment of any investigational pharmacologic agent, imaging materials, including dyes, investigational surgical techniques, or devices.
12. Chemotherapy or other anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to initiation of study treatment.
13. Radiotherapy < 2 weeks prior to enrollment. Patients with wide-field radiotherapy (> 30% of marrow-bearing bone) must not have had treatment within 4 weeks prior to initiation of study treatment.

14. Major surgery within 21 days prior to signing ICF unless the patient has recovered at that time.

    Note: Major surgery involves opening of a body cavity such as the thorax or abdomen. A lymph node or skin biopsy is not considered major surgery. Minor surgical procedures such as central venous catheter placement, tumor biopsy, and feeding tube placement are not considered major.

15. Active ILD/pneumonitis or history of noninfectious ILD/pneumonitis/radiation pneumonitis that required steroid treatment.
16. Oxygen saturation of < 93% on room air at rest
17. Resting QTcF > 470 msec. If a single QTcF is > 470 msec, the patient may enroll if the mean QTcF from 3 electrocardiograms (ECGs) is < 470 msec.
18. History of nephrotic syndrome or proteinuria Grade ≥ 2.
19. Active corneal disease, or history of corneal disease within 4 months prior to enrollment.
20. Active, uncontrolled or severe impairment of the urogenital, renal, hepatobiliary, cardiovascular, respiratory, gastrointestinal, neurologic, or hematopoietic systems which, in the opinion of the INV, would predispose the patient to the development of complications from the administration of protocol therapy.
21. 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.
22. Documented other concurrent nonmalignant 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 (New York Heart Association III or IV).
23. Any concurrent anticancer chemotherapy, radiotherapy (palliative radiation may be permitted after approval by the sponsor in accordance with protocol), hormonal therapy, immunotherapy, corticosteroid therapy other than that permitted in protocol), or any other prohibited medications as listed in protocol.
24. Live vaccines within 30 days prior to study enrollment.
25. Concomitant use of strong inhibitors or strong inducers of cytochrome P450 (CYP)3A4.
26. For Phase 1 only: Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure with reduced ejection fraction or severe diastolic dysfunction, potential for torsades de pointes, congenital long QT syndrome.
27. Positive for hepatitis B surface antigen (HbsAg) or hepatitis B (HBV) DNA.
28. Active acute or chronic infection.

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Dose Escalation of TUB-040; Participants will receive escalating doses of TUB-040 to determine recommended Phase 2 dose (RP2D).	Drug: TUB-040 - Dose escalation; TUB-040 will be administered as an intravenous (IV) solution on day 1 of each treatment cycle.
Experimental: Phase 2: Monotherapy of TUB-040; Participants in Phase 2 will receive the recommended dose of TUB-040 monotherapy determined in Phase	Drug: TUB-040 - RP2D; TUB-040 will be administered as an intravenous (IV) solution on day 1 of each treatment cycle. Dose based on the RP2D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)	Incidence and severity of treatment-emergent adverse events (TEAEs)	Up to 3 years
Phase 1: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs)	Incidence of dose-limiting toxicities (DLTs) at each dose level	Up to 3 years
Phase 2: Overall Response Rate (ORR)	Investigator (INV) assessment of overall response rate (ORR) by Response Evaluation Criteria for Solid Tumors (RECIST) v1.1	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Overall Response Rate (ORR)	Investigator (INV) assessment of overall response rate (ORR) by Response Evaluation Criteria for Solid Tumors (RECIST) v1.1	Up to 3 years
Phase 1: Duration of Response (DOR)	Investigator (INV) assessment of duration of response (DOR) by Response Evaluation Criteria for Solid Tumors (RECIST) v1.1	Up to 3 years
Phase 1: Progression-Free Survival (PFS)	Investigator (INV) assessment of progression-free survival (PFS) by Response Evaluation Criteria for Solid Tumors (RECIST) v1.1	Up to 3 years
Phase 1: Disease Control Rate (DCR)	Investigator (INV) assessment of disease control rate (DCR) by Response Evaluation Criteria for Solid Tumors (RECIST) v1.1	Up to 3 years
Phase 1: Overall Survival (OS)	Overall Survival (OS)	Up to 3 years
Phase 1: Change From Baseline in Fridericia's Corrected QT interval (QTcF)	Change from baseline in QTcF	Up to 3 years
Phase 1: Pharmacokinetic (PK) parameter: Cmax	Cmax is defined as: Maximum plasma/serum concentration (Cmax)	Up to 3 years
Phase 1: Pharmacokinetic (PK) parameter: Tmax	Tmax is defined as: Time to Cmax	Up to 3 years
Phase 1: Pharmacokinetic (PK) parameter: AUC	AUC is defined as: Area under the concentration time curve (AUC)	Up to 3 years
Phase 1: Pharmacokinetic (PK) parameter: t1/2	t1/2 is defined as: If data collected allows estimated half-life	Up to 3 years
Phase1/Phase2: Percentage of Participants Who Develop Anti-TUB-040 Antibodies as appropriate	Number and percentage of patients who develop anti-TUB-040 antibodies and a semiquantitative assessment of titer	Up to 3 years
Phase 2: Durability of Response (DOR)	Investigator (INV) assessment of durability of response (DOR) by Response Evaluation Criteria for Solid Tumors (RECIST) v1.1	Up to 3 years
Phase 2: Progression-Free Survival (PFS)	Investigator (INV) assessment of progression-free survival (PFS) by Response Evaluation Criteria for Solid Tumors (RECIST) v1.1	Up to 3 years
Phase 2: Disease Control Rate (DCR)	Investigator (INV) assessment of disease control rate (DCR) by Response Evaluation Criteria for Solid Tumors (RECIST) v1.1	Up to 3 years
Phase 2: Overall Survival (OS)	Overall Survival (OS)	Up to 3 years
Phase 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)	Incidence and severity of treatment emergent adverse events (TEAEs)	Up to 3 years

Collaborators and Investigators

• Sponsor: Tubulis GmbH
• Investigators: Study Director: Tubulis Medical Director, Tubulis GmbH

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: July 30, 2026
• First Submitted That Met QC Criteria: July 30, 2026
• First Posted (Actual): August 4, 2026

Study Record Updates

• Last Update Posted (Actual): August 5, 2026
• Last Update Submitted That Met QC Criteria: August 3, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Recurrent Endometrial Cancer; Progressive Endometrial Cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms
• Other Study ID Numbers: NAPISTAR 1-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No