| Eligibility |
Inclusion Criteria:
1. Has an advanced, histologically-proven solid tumor of one of the following types, and
for which approved therapies have been exhausted or for which the Investigator
considers the patient ineligible or unable to tolerate other treatments:
1. Colorectal cancer
2. Ovarian cancer
3. Endometrial cancer
4. Gastric cancer
5. Pancreatic cancer
6. Anal cancer
7. Cervical cancer
8. Head and neck squamous cell carcinoma (HNSCC)
9. Mesothelioma
10. Prostate cancer
11. Non-small cell lung cancer (NSCLC)
12. Melanoma
13. Urothelial/bladder cancer
14. Microsatellite instability high cancer of any type
15. Cutaneous squamous cell cancer
16. Breast cancer
2. Has signed and dated written informed consent before performing any study procedure,
including screening
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1
4. Anticipated life expectancy = 12 weeks by Investigator judgement
5. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1
6. Should agree to undergo mandatory paired (pre and on-treatment) tumor biopsies and be
considered to have biopsiable disease. The biopsies should be performed as follows:
1. At least 1 tumor lesion = 20 mm amenable to percutaneous biopsy other than the
target lesion(s) used to follow response as defined by RECIST v1.1.
2. For cutaneous or subcutaneous lesions, tumors should be = 5 mm in diameter
amenable to biopsy by excisional or punch biopsies without unacceptable risk of a
major procedural complication.
3. For core needle biopsy specimens, at least 3 to 6 cores with an 18-gauge needle
should be collected.
4. The on-treatment tumor biopsy should be taken from the same lesion as the
pre-treatment biopsy. The biopsied lesion should be large enough to take both
biopsies = 1 cm apart.
7. Should agree to undergo mandatory paired (pre and on-treatment) skin biopsies
8. At least 28 days must have elapsed between any prior major surgery and screening. The
following procedures are not considered major:
1. Obtaining the pre-treatment tumor and skin biopsies as per protocol requirements
2. Placement of a port for central venous access
3. Needle, punch or excisional biopsy of a clinically or radiographically detected
lesion
9. Laboratory parameters at screening:
a. Hematology: i. Platelet count = 100,000 cells/mm3 ii. Absolute neutrophil count =
1,000 cells/mm3 iii. Hemoglobin = 9 g/dL b. Serum creatinine < 1.5 x upper limit of
normal (ULN) or creatinine clearance > 50 mL/min on the basis of Cockcroft-Gault
glomerular filtration rate estimation c. Coagulation: i. International normalized
ratio (INR) < 1.5 ii. Prothrombin time (PT) and activated partial thromboplastin time
(aPTT) = 1.5 x ULN unless therapeutically warranted d. Aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) < 3 x ULN e. Bilirubin normal, except for
patients with known familial hyperbilirubinemia (such as Gilbert syndrome); for
patients with documented Gilbert's syndrome (Gilbert-Meulengracht syndrome) total
bilirubin = 3 x ULN is acceptable f. Albumin > 2.8 g/dL or > 28 g/L, and without
albumin transfusion for = 7 days before screening
10. Is using highly effective contraception, for females of childbearing potential (FCBP)
and for men, as follows:
1. Female: Is not pregnant, is not breastfeeding, and one of the following applies:
- Not a FCBP
- A FCBP who agrees and/or whose male partner agrees to follow the
contraceptive guidance from screening, during the treatment period, and for
at least 3 months after the last study drug administration. A FCBP must have
a negative serum pregnancy test result at screening.
Male: Agreement to use a highly effective contraception method from screening, during the
treatment period, and for at least 3 months after the last study drug administration and to
refrain from donating sperm during this period.
Exclusion criteria:
1. Known hypersensitivity to excipients used in the MP0317 formulation
2. Autoimmune diseases, except autoimmune endocrinopathies that are stable with hormone
replacement therapy
3. Inflammatory diseases such as arthritis, colitis, liver fibrosis, cirrhosis,
interstitial fibrosis or chronic obstructive pulmonary disease (COPD) that may have
elevated tissue fibroblast activation protein (FAP) expression unless approved after
consultation with the Sponsor
4. Serious illness or concomitant non-oncological disease considered by the Investigator
to be incompatible with participating in the protocol
5. Left ventricular ejection fraction of < 50% on echocardiographic exam or multi-gated
acquisition (MUGA) scan at screening
6. History or evidence of clinically significant cardiovascular disease defined as at
least one of the following criteria:
1. Evidence of poorly controlled arterial hypertension (systolic blood pressure >
160 mmHg or diastolic blood pressure > 100 mmHg)
2. Myocardial infarction or instable angina pectoris within 6 months before
screening
3. Heart failure (New York Heart Association Class III or IV)
4. Any cardiac arrhythmia that is not well controlled
5. QT corrected (QTc) prolongation = Grade 2 (> 480 ms) at screening measured on 2
separate electrocardiograms (ECG) at least 10 minutes apart
6. Clinically significant valvular heart disease
7. Severe dyspnea, pulmonary dysfunction or need for continuous supportive oxygen
inhalation
8. Arterial thromboembolic event, stroke or transient ischemia attack within 12 months
before screening
9. Known central nervous system (CNS) metastases that are either untreated or are treated
but are associated with clinical symptoms (e.g. headache, convulsions); patients with
CNS metastases that have been treated with radiotherapy and/or surgery are eligible if
they are clinically without symptoms for at least 6 weeks before screening; if under
treatment with corticosteroids (not exceeding 10 mg/day prednisone or equivalent)
and/or anticonvulsive agents, patients must be on a stable dose for at least 14 days
before first study drug administration.
10. Active uncontrolled bleeding or a bleeding diathesis
11. Therapy for active infection needs to be completed at least 7 days before first study
drug administration
12. Known positivity for human immunodeficiency virus (HIV) or history of HIV (HIV testing
is not mandatory)
13. Active hepatitis B (chronic or acute; HBV) defined as having a positive hepatitis B
surface antigen (HBsAg) test at screening. Patients with past or resolved HBV
infection (defined as having a negative HBsAg test and a positive hepatitis B core
antigen antibody test) are eligible.
14. Active hepatitis C (HCV) infection defined as having a positive HCV antibody test
followed by a positive HCV ribonucleic acid (RNA) test at screening. The HCV RNA test
will be performed only for patients who have a positive HCV antibody test. Patients
who are positive for HCV antibodies are eligible only if polymerase chain reaction
(PCR) is negative for HCV RNA.
15. Serious or non-healing wound, skin ulcer or non-healing bone fracture
16. Abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6
months before screening
17. Any vaccines within 28 days before first study drug administration
18. An allogenic tissue/solid organ transplant
19. History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease = 2
years before screening and of relatively low potential risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of residual disease
3. Adequately treated carcinoma in situ without evidence of disease
4. Cancer patients with incidental histologic findings of prostate cancer that, in
the opinion of the Investigator, is not deemed to require active therapy (e.g.
incidental prostate cancer identified following cystoprostatectomy that is
tumor/node/metastasis Stage = pT2N0) may be eligible, pending discussion and
approval by the Sponsor
20. Previous treatment with a DARPin® molecule
21. Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study, or it is the follow-up period of an
interventional study
22. Use of an investigational agent within 28 days before first study drug administration
23. Any anticancer treatment, including chemotherapy, hormonal therapy or radiotherapy,
within 21 days before first study drug administration; however, the following are
allowed:
1. Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists or
antagonists
2. Hormone-replacement therapy or oral contraceptives
3. Palliative radiotherapy for bone metastases within 14 days before first study
drug administration
24. Continuous corticosteroid use exceeding 10 mg/day prednisone or equivalent
25. Any condition that, in the opinion of the Investigator, would interfere with
evaluation of the investigational medicinal product (IMP) or interpretation of the
patient's data
26. Unable or unwilling to comply with all study requirements for clinical visits,
examinations, tests and procedures
27. Patient deprived of liberty by a judicial or administrative decision, patient admitted
to a social institution or who is under a measure of legal protection, patient
hospitalized without consent or who is in an emergency situation
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