The purpose of this multicentric, open label trial (NAPISTAR 1-01) is 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 an antibody-drug-conjugate which delivers a topoisomerase I inhibitor to tumor cells which overexpress the target NaPi2b. The study consists of two parts: In dose escalation, ovarian cancer patients and lung cancer patients receive increasing doses of TUB-040 until the maximal tolerated dose is found. In dose optimization, at least two doses are compared with each other to determine which dose is optimal for patients.

TUB-040 is given IV every 3 weeks until the disease progresses or the patient has to stop due to side effects.

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)

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