A Multicenter, First-in-human Dose Escalation and Optimization Phase I/IIa Study to Investigate Safety, Tolerability, PK, and Efficacy of the NaPi2b ADC TUB-040 in Patients With Platinum-resistant High-grade Ovarian Cancer (PROC) or r/r Adenocarcinoma Non-small Cell Lung Cancer (NSCLC)
Study Identifier:
NAPISTAR 1-01
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
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Study Summary
To evaluate the safety/tolerability, pharmacokinetics and preliminary efficacy of TUB-040 and to find the best dose of TUB-040 in patients with ovarian cancer and Non Small Cell Lung Cancer
TUB-040 is given IV every 3 weeks until the disease progresses or the patient has to stop due to side effects.
To determine the maximal tolerated dose (MTD) and refine dosing as pre-defined safety parameters are met. Phase IIa involves the randomization of patients for dose optimization at two or more doses to further characterize the safety profile and identify the optimal therapeutic dose.
To evaluate TUB-040 in PROC-HGSOC and in adenocarcinoma non-small cell lung cancer (NSCLC).
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Non-Small Cell Lung Cancer
Ovarian
Fallopian Tube
Primary Peritoneal
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
N/A
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Inclusion Criteria (for all patients)
- Male or non-pregnant, non-breastfeeding female, age 18 years or older at the date of consent.Disease not amenable to curative intent treatment.Participants 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.Participants 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.Participants must be willing to sign an archival tissue release form for research purposes and determination of biomarker expression.Participants 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 functionResolution 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 IOs).Participants 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 participants assigned female at birth.In the opinion of the investigator, the participant must be able to understand, give written informed consent, and comply with all study-related procedures, medication use, and evaluations.The participant must not have a history of non-compliance with medical regimens or be considered potentially unreliable and/or uncooperative.The participant must be willing to sign and date the informed consent form (ICF)
- OVARIAN CANCER • Histologically confirmed high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer . Have PROC defined as: Patients who have only received one line of platinum-based chemotherapy (PBC) must have received at least three cycles of PBC and then progressed between 30 and 183 days after the date of the last dose of PBC Patients who have received two to five lines of prior PBC must have progressed during or within 183 days after the date of the last dose of PBC Have received no more than 5 lines of PBC and 2 lines of non-PBC in PROC
Exclusion criteria
- Exclusion Criteria (for all patients)
- The participant is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.History of hypersensitivity to exatecan or excipients of the TUB-040 formulation.Participants 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.Participants with spinal cord compression or active central nervous system disease, and/or carcinomatous meningitis.Prior radiotherapy <2 weeks from trial inclusion.Major surgery within 21 days prior to signing the ICF, unless the participant is recovered at that time.Has a history of non-infectious ILD/pneumonitis/radiation pneumonitis that required steroids or has current ILD/pneumonitis.Has an oxygen saturation of <93% on room air at rest.Has a QTcF >470 msHistory of nephrotic syndromeActive corneal disease, or history of corneal disease within 12 months prior to enrollment.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 participant 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.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).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.Concurrent use of strong inhibitors or strong inducers of CYP3A4Live vaccines within 30 days prior to study entry.Participants with acute or chronic infections such as:Participants who are HBsAg positive are eligible if they have received HBV anti-viral therapy for at least 4 weeks and have an undetectable HBV viral load prior to randomization.Participants with a history of HCV infection are eligible if HCV viral load is undetectable at screening.HIV infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/diseaseAny 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 leukoencephalopathyNote: Other protocol defined Inclusion/Exclusion criteria may apply.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START New Jersey
East Brunswick, NJ, United States, 08816
Investigator
Bruno Fang
Status
Will Be Recruiting
Condition(s) Treated at Site
Non-Small Cell Lung Cancer
Ovarian
Fallopian Tube
Primary Peritoneal
Location
START Mountain Region
West Valley City, UT, United States, 84119
Investigator
Justin Call
Status
Recruiting
Condition(s) Treated at Site
Non-Small Cell Lung Cancer
Ovarian
Fallopian Tube
Primary Peritoneal