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

Prior treatment

• Individuals 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.
• Prior radiotherapy \<2 weeks from trial inclusion.
• Major surgery within 21 days prior to signing the ICF, unless the individual is recovered at that time.
• Active corneal disease, or history of corneal disease within 12 months prior to enrollment.
• 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).
• Concurrent use of strong inhibitors or strong inducers of CYP3A4
• Live vaccines within 30 days prior to study entry.
• Individuals with acute or chronic infections such as:
  • Individuals who are HBsAg positive are eligible if they have received Hepatitis B virus (HBV) anti-viral therapy for at least 4 weeks and have an undetectable HBV viral load prior to randomization.
  • Individuals with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.
  • HIV infected individuals must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease
  • Any other known unresolved and active bacterial, viral, fungal, mycobacterial, or other infection at screening.
  • History of severe and recurrent infections per INV judgment.
  • History of progressive multifocal leukoencephalopathy
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Other illness

• History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.
• Individuals with spinal cord compression or active central nervous system disease, and/or carcinomatous meningitis.
• Has a history of non-infectious interstitial lung disease/pneumonitis (ILD)/pneumonitis/radiation pneumonitis that required steroids or has current ILD/pneumonitis.
• History of nephrotic syndrome
• Active, uncontrolled or severe impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic, or hematopoietic systems which, in the opinion of the investigator, would predispose the individual 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.
• Any anti-tumor chemotherapy, systemic anti-cancer therapy, radiotherapy (except for local radiation therapy of lesions that may cause imminent complications), hormonal therapy, immunotherapy, or corticoid therapy.

Lab values

• The individual is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.

Other

• Has an oxygen saturation of \<93% on room air at rest.
• Has a QTcF \>470 ms

• Male or non-pregnant, non-breastfeeding female, age 18 years or older at the date of consent.
• Disease not amenable to curative intent treatment.
• Individuals 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.
• Individuals with previous systemic topoisomerase I inhibitor treatment (e.g., Topotecan) are allowed in the study.
• Radiologically measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the INV.
• 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.
• Individuals must be willing to sign an archival tissue release form for research purposes and determination of biomarker expression.
• Individuals 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 or anticancer treatment such as but not limited to immune oncology therapy (IOs)).
• Individuals 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 individuals assigned female at birth.
• In the opinion of the investigator, the individual must be able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations.
• The individual must not have a history of non-compliance with medical regimens or be considered potentially unreliable and/or uncooperative.
• The individual must be willing to sign and date the informed consent form (ICF)