Study of TUB-040 in Participants With Unresectable or Metastatic Nonsquamous Non-small Cell Lung Cancer

A Randomized, Open-label, Phase 2a Dose Optimization Study of TUB-040 (a NaPi2b Antibody-drug Conjugate) in Participants With Unresectable or Metastatic Nonsquamous Non-small Cell Lung Cancer

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 unresectable or metastatic non-small cell lung cancer (NSCLC).

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

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC; Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: TUB-040

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

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
      • Contact: START Los Angeles; Email: ct-inquiries@tubulis.com
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • START New Jersey
      • Contact: START New Jersey; Email: ct-inquiries@tubulis.com

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Adults, male or nonpregnant, nonbreastfeeding female, age ≥18 years at the date of consent.
2. Eastern Cooperative Oncology Group performance status of 0 or 1.
3. Documented radiographic progression on or after the most recent line of anticancer therapy.
4. Life expectancy of more than 12 weeks for disease-related mortality as evaluated by the INV.
5. At least 1 radiologically measurable lesion by RECIST v1.1, which can include a lesion in an irradiated field that shows progression according to RECIST v1.1.
6. Stable metastases to the central nervous system (CNS) are eligible only after definitive therapy (such as surgery, radiotherapy, stereotactic therapy) was provided and the individual is asymptomatic and off systemic steroids and anticonvulsants. Individuals with treated brain metastases that are no longer symptomatic may be included if they have recovered from the acute toxic effects of radiotherapy. A minimum of 7 days for targeted radiation and 14 days for whole brain radiation must have elapsed prior to Cycle 1 Day 1.

7. Adequate hematologic function as indicated by:

   1. Platelet count ≥ 100,000/mm3 (no platelet transfusion or growth factors, eg, eltrombopag, romiplostim, or interleukin-11 within 4 weeks before the first dose of study treatment)
   2. Hemoglobin ≥ 9.0 g/dL (no packed red blood cell transfusion or growth factors [eg, erythropoietin, darbepoetin] within 4 weeks before the first dose of study treatment and/or long-acting white blood cell growth factors within 28 days before first dose of study treatment)
   3. Absolute neutrophil count ≥ 1500/μL (no growth factors [eg, granulocyte colony stimulating factor, granulocyte macrophage-colony stimulating factor] within 4 weeks before the first dose of study treatment)
   4. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 × upper limit of normal (ULN) in the absence of anticoagulation therapy. If individuals are on anticoagulation therapy with a specific INR goal, INR should be within the therapeutic range for the medical indication

8. Adequate hepatic function as defined by a total bilirubin level ≤ 1.5 × ULN, aspartate aminotransferase (AST) level ≤ 2.5 × ULN, and alanine aminotransferase (ALT) level ≤ 2.5 × ULN.

   1. For documented Gilbert's syndrome, a total bilirubin < 3 × ULN is acceptable
   2. For individuals with liver metastases, AST and ALT < 5 × ULN is acceptable
9. 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 metastases.
10. Adequate renal function defined by glomerular filtration rate (GFR) ≥ 50 mL/min (according to the Chronic Kidney Disease Epidemiology Collaboration formula).
11. Resolution of all adverse events (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 individuals 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).

12. Completed washout of prior therapy:

    1. Systemic anticancer therapy within 5 half-lives or 4 weeks, whichever is shorter, prior to first dose of study treatment. Hormonal therapy is not considered anticancer therapy.
    2. Radiotherapy ≥ 2 weeks prior to the first dose of study treatment
13. Willing to undergo a noncontrast high-resolution computed tomography scan of the chest and pulmonary function tests at screening.
14. Individuals with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening and they have completed curative antiviral therapy at least 4 weeks before enrollment.
15. 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 unless they have undergone permanent sterilization (ie, hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or are postmenopausal.
16. 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.
17. Ability to understand, give written informed consent, comply with all study-related procedures, medication use, and assessments
18. No history of noncompliance with medical regimens or considered, in the opinion of the INV, to be potentially unreliable and/or uncooperative.

Key Exclusion Criteria:

1. Mixed histology NSCLC (eg, small cell lung cancer/NSCLC) or histology other than adenocarcinoma
2. Prior pneumonectomy
3. Newly identified or known unstable brain metastases, spinal cord compression, active CNS disease, progressive multifocal leukoencephalopathy, and/or carcinomatous meningitis.
4. Pregnant, lactating, or breastfeeding.
5. History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.
6. Prior treatment with an ADC-containing topoisomerase 1 (Topo-1) inhibitor payload (or other camptothecin derivatives) or any ADC targeting NaPi2b. ADCs with other payloads are allowed (eg, monomethyl auristatin E, monomethyl auristatin F, etc.).
7. Discontinuation of the most recent systemic anticancer therapy due to hematologic toxicity.
8. Concomitant use of strong inhibitors or strong inducers of cytochrome P450 3A4.
9. 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.
10. Radiotherapy < 2 weeks prior to start of study treatment (planned C1D1), except in the case of stereotactic radiation to the brain, in which case the required interval is 7 days.
11. Major surgery within 21 days prior to signing ICF.
12. Active interstitial lung disease (ILD)/pneumonitis or history of noninfectious ILD/pneumonitis/radiation pneumonitis requiring steroid treatment.
13. Resting Fridericia's corrected QT interval (QTcF) > 470 msec. If a single QTcF is > 470 msec, the patient may enroll if the mean QTcF from 3 electrocardiograms (ECG) is < 470 msec.
14. History of nephrotic syndrome or proteinuria Grade ≥ 2.
15. Active keratitis or corneal disorder or history of corneal disease including history of herpes simplex virus keratitis within 4 months prior to enrollment.
16. 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 individual to the development of complications from the administration of protocol therapy.
17. Documented 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 unstable or worsening congestive heart failure (New York Heart Association III or IV).
18. Any concurrent anticancer chemotherapy, radiotherapy (palliative radiation may be permitted after approval by the sponsor), hormonal therapy, immunotherapy, biologic, or corticosteroid therapy.
19. Live attenuated vaccines within 30 days prior to study enrollment.
20. Positive for hepatitis B surface antigen or hepatitis B DNA.
21. Acute, chronic, or severe recurrent infections (per INV's judgment) of active bacterial, viral, fungal, mycobacterial, or other infection of ≤ 14 days after systemic anti-infective treatment prior to randomization.

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NSCLC Dose 1; Participants will receive TUB-040 administered as an intravenous (IV) infusion on Day 1 of each treatment cycle. Until disease progression, unacceptable toxicity, or withdrawal of consent.	Drug: TUB-040; Administered IV
Experimental: NSCLC Dose 2; Participants will receive TUB-040 administered as an IV infusion on Day 1 of each treatment cycle. Until disease progression, unacceptable toxicity, or withdrawal of consent.	Drug: TUB-040; Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	Incidence and severity of treatment-emergent adverse events (TEAEs)	From enrollment until 30 days after last dose of study drug
Overall Response Rate (ORR)	Assessment of overall response rate (ORR) by Response Evaluation Criteria for Solid Tumors (RECIST) v1.1 as assessed by the investigator (INV)	Enrollment until approximately 80 days since last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DoR)	Duration of response (DoR) by RECIST v1.1 as assessed by the INV	Up to approximately 24 months
Disease control rate (DCR)	Disease control rate (DCR) by RECIST v1.1 as assessed by the INV	Up to approximately 24 months
Progression-free survival (PFS)	Progression-free survival (PFS) by RECIST v1.1 as assessed by the INV	Up to approximately 24 months
Overall survival (OS)	Overall survival (OS)	Up to approximately 24 months
Pharmacokinetic (PK) Parameter: Cmax of TUB-040	PK parameter of Maximum plasma/serum concentration (Cmax) of TUB-040	Up to approximately 24 months
Pharmacokinetic (PK) Parameter: Tmax	PK parameter of Time to Cmax for TUB-040	Up to approximately 24 months
Pharmacokinetic (PK) Parameter: AUC	PK parameter of Area under the concentration-time curve (AUC) for TUB-040	Up to approximately 24 months
Pharmacokinetic (PK) Parameter: t1/2	PK parameter of Estimated half-life (t1/2) of TUB-040, if data collected allow	Up to 3 yeaUp to approximately 24 months
Percentage of Participants Who Develop Anti-TUB-040 Antibodies	Number and percentage of participants who develop anti-TUB-040 antibodies and a semiquantitative assessment of titer	Up to approximately 24 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: September 1, 2026
• First Submitted That Met QC Criteria: September 1, 2026
• First Posted (Actual): September 8, 2026

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 5, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NAPISTAR 2-01

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