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
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests TUB-040 in adults with a type of non-small cell lung cancer called adenocarcinoma that cannot be removed by surgery or has spread. It checks how safe the drug is, how well it works, how the body handles it, and what dose to use in the next study phase.
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).
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be age 18 or older and able to do daily tasks with little or no help.
- Have scans showing that the cancer grew during or after the most recent cancer treatment, with at least one tumor that can be measured.
- Be expected by the study doctor to live more than 12 weeks.
- Meet the study’s blood count, blood clotting, liver, and kidney test limits.
- If cancer has spread to the brain or spinal cord, it must be treated and stable, with no symptoms and no use of whole-body steroids or seizure medicines. Required waiting times after radiation apply.
- Have recovered from most past treatment side effects and completed the required breaks from past cancer treatment.
- Agree to a chest CT scan, breathing tests, and other study steps, and give written consent.
- If able to become pregnant, have a negative pregnancy test, do not breastfeed or plan pregnancy, and use highly effective birth control during the study and for 6 months afterward.
Who can't join
- Have lung cancer other than adenocarcinoma, mixed types of lung cancer, or a past surgery to remove an entire lung.
- Have new or unstable cancer in the brain, pressure on the spinal cord, or certain other active brain or spinal cord diseases.
- Be pregnant or breastfeeding, or have an allergy to exatecan or ingredients in TUB-040.
- Have received certain antibody-drug conjugates, which deliver cancer drugs to cells, or related drugs. Stopping the latest cancer treatment because of harmful effects on blood cells also rules out joining.
- Have active lung inflammation, or past lung inflammation not caused by infection that needed steroids; certain kidney problems; or certain diseases of the cornea, the clear front of the eye.
- Have certain heart rhythm problems, serious heart disease, or other severe or uncontrolled health problems that could make treatment unsafe.
- Have positive hepatitis B tests or certain active or recent infections.
- Have certain recent treatments, another research study, major surgery within 21 days before consent, or a live vaccine within 30 days before joining. Some medicines and cancer treatments taken during the study are also not allowed.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
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 sites (2)
CA
- START Los Angeles · Los Angeles, CA 90025START Los Angeles · Study contact · ct-inquiries@tubulis.comMore trials in Los Angeles
NJ
- START New Jersey · East Brunswick, NJ 08816START New Jersey · Study contact · ct-inquiries@tubulis.comMore trials in East Brunswick