A 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:
NCT06303505
EudraCT Identifier:
2024-511074-80
EU Trial (CTIS) Number:
2024-511074-80-01
Study Contact Information:
(210) 593-5651 or [email protected]
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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.
Ovarian
Non-Small Cell Lung Cancer
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)
  • 1. Male or non-pregnant, non-breastfeeding female, age 18 years or older at the date of
  • consent.
  • 2. Disease not amenable to curative intent treatment.
  • 3. Patients 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.
  • 4. Radiologically measurable disease by Response Evaluation Criteria in Solid Tumors
  • (RECIST) 1.1, that includes at least 1 lesion not previously irradiated.
  • 5. Eastern Cooperative Oncology Group (ECOG) 0-1.
  • 6. Have a life expectancy of more than 12 weeks for disease-related mortality, as
  • evaluated by the INV.
  • 7. Patients must be willing to sign an archival tissue release form for research purposes
  • and determination of biomarker (eg NaPi2b) expression.
  • 8. Patients must be willing to undergo a non-contrast high resolution computed tomography
  • (HRCT) of the thorax scan and pulmonary function testing (PFT) at screening.
  • 9. Adequate organ function
  • 10. 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).
  • 11. Patients 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 patients
  • assigned female at birth. Abstinence is acceptable only as true abstinence when this
  • is in line with the preferred and usual lifestyle of the patient for the duration of
  • the study treatment and the above-referred period after the end of the exposure.
  • Periodic abstinence (e.g., calendar ovulation, symptothermal, post-ovulation methods),
  • the rhythm method, and the withdrawal method are not acceptable methods of
  • contraception.
  • 12. In the opinion of the investigator, the patient must be able to understand, give
  • written informed consent, and comply with all study-related procedures, medication
  • use, and evaluations.
  • 13. The patient must not have a history of non-compliance with medical regimens or be
  • considered potentially unreliable and/or uncooperative.
  • 14. The patient 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)
  • 1. The patient is pregnant, lactating or breastfeeding or has a positive serum pregnancy
  • test during the screening period.
  • 2. History of hypersensitivity to exatecan or excipients of the TUB-040 formulation,
  • including ADCs with deruxtecan, exatecan or camptothecan as a payload.
  • 3. Disease that is refractory to topoisomerase-I inhibitors, defined as progression
  • during or within 6 months of the last infusion.
  • 4. Patients 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.
  • 5. Patients with spinal cord compression or active central nervous system disease.
  • 6. Prior radiotherapy <2 weeks from trial inclusion.
  • 7. Major surgery within 21 days prior to signing the ICF, unless the patient is recovered
  • at that time.
  • 8. Has a history of non-infectious ILD/pneumonitis/radiation pneumonitis that required
  • steroids or has current ILD/pneumonitis.
  • 9. Has an oxygen saturation of <93% on room air at rest.
  • 10. Has a forced vital capacity of <60% and diffusing capacity of the lung for carbon
  • monoxide <70%.
  • 11. Has a QTcF >470 ms
  • 12. History of nephrotic syndrome
  • 13. Active corneal disease, or history of corneal disease within 12 months prior to
  • enrollment.
  • 14. Active, uncontrolled impairment of the urogenital, renal, hepatobiliary,
  • cardiovascular, gastrointestinal, neurologic, or hematopoietic systems which, in the
  • opinion of the investigator, would predispose the patient to the development of
  • complications from the administration of protocol therapy.
  • 15. 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.
  • 16. 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).
  • 17. Any concurrent chemotherapy, radiotherapy (except for local radiation therapy of
  • lesions that may cause imminent complications), immunotherapy, or corticoid therapy.
  • 18. Live vaccines within 30 days prior to study entry.
  • 19. Patients with acute or chronic infections such as:
  • 1. Patients 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.
  • 2. Patients with a history of HCV infection are eligible if HCV viral load is
  • undetectable at screening.
  • 3. HIV infected patients must be on anti-retroviral therapy (ART) and have a
  • well-controlled HIV infection/disease
  • 4. Any other known unresolved and active bacterial, viral, fungal, mycobacterial, or
  • other infection at screening.
  • 5. History of severe and recurrent infections per INV judgment.
  • 6. History of progressive multifocal leukoencephalopathy

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
Ovarian
Non-Small Cell Lung Cancer
Location
START Mountain Region
West Valley City, UT, United States, 84119
Investigator
Justin Call
Status
Will Be Recruiting
Condition(s) Treated at Site
Ovarian
Non-Small Cell Lung Cancer