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

NCT07806773 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NAPISTAR 2-01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

NSCLC; Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Duration of response (DoR)

  Up to approximately 24 months

• Disease control rate (DCR)

  Up to approximately 24 months

• Progression-free survival (PFS)

  Up to approximately 24 months

• Overall survival (OS)

  Up to approximately 24 months

• Pharmacokinetic (PK) Parameter: Cmax of TUB-040

  Up to approximately 24 months

Study Arms (2)

NSCLC Dose 1

EXPERIMENTAL

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

NSCLC Dose 2

EXPERIMENTAL

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

Interventions

TUB-040 DRUG

Administered IV

NSCLC Dose 1; NSCLC Dose 2

Eligibility Criteria

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

You may qualify if:

• Adults, male or nonpregnant, nonbreastfeeding female, age ≥18 years at the date of consent.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Documented radiographic progression on or after the most recent line of anticancer therapy.
• Life expectancy of more than 12 weeks for disease-related mortality as evaluated by the INV.
• 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.
• 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.
• Adequate hematologic function as indicated by:
• 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)
• 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)
• 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)
• 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
• 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.
• For documented Gilbert's syndrome, a total bilirubin \< 3 × ULN is acceptable
• For individuals with liver metastases, AST and ALT \< 5 × ULN is acceptable
• 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.

You may not qualify if:

• Mixed histology NSCLC (eg, small cell lung cancer/NSCLC) or histology other than adenocarcinoma
• Prior pneumonectomy
• Newly identified or known unstable brain metastases, spinal cord compression, active CNS disease, progressive multifocal leukoencephalopathy, and/or carcinomatous meningitis.
• Pregnant, lactating, or breastfeeding.
• History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.
• 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.).
• Discontinuation of the most recent systemic anticancer therapy due to hematologic toxicity.
• Concomitant use of strong inhibitors or strong inducers of cytochrome P450 3A4.
• 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.
• 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.
• Major surgery within 21 days prior to signing ICF.
• Active interstitial lung disease (ILD)/pneumonitis or history of noninfectious ILD/pneumonitis/radiation pneumonitis requiring steroid treatment.
• 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.
• History of nephrotic syndrome or proteinuria Grade ≥ 2.
• Active keratitis or corneal disorder or history of corneal disease including history of herpes simplex virus keratitis within 4 months prior to enrollment.

Sponsors & Collaborators

• Tubulis GmbH: lead

Study Sites (2)

START Los Angeles

Los Angeles, California, 90025, United States

Location

START New Jersey

East Brunswick, New Jersey, 08816, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Tubulis Medical Director

  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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2026
• First Posted: September 8, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: September 16, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)