| Eligibility |
Inclusion criteria:
1. Patient has an advanced, histologically-proven solid tumor of one of the following
types, treated with at least one line of systemic therapy, and for which approved
therapies have been exhausted or for which the Investigator considers the patient
ineligible or intolerant of other forms of treatment: Colorectal, Ovarian,
Endometrial, Gastric, Pancreatic, Anal, Cervical, Squamous cell cancer of the head and
neck, Mesothelioma, Prostate, Non-small cell lung cancer, Melanoma,
Urothelial/bladder, Microsatellite instability high tumors of any type, Cutaneous
squamous cell, Breast,
2. Patients have to be willing to comply with study procedures
3. =18 years of age
4. Mentally competent, able to understand and willing to sign the ICF
5. Eastern Cooperative Oncology Group performance status (ECOG; PS) =1
6. Anticipated life expectancy =12 weeks by Investigator judgment
7. The disease is measurable according to Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1 criteria
8. Mandatory paired pre- and on-treatment biopsies - preferably from the same lesion -
are required as follows:
1. At least 1 tumor lesion =10 mm amenable to percutaneous biopsy other than the
target lesion used to follow response as defined by RECIST v1.1
2. For cutaneous or subcutaneous lesions, tumors should be = 5mm in diameter
amenable to paired biopsy by excisional or punch biopsies without unacceptable
risk of a major procedural complication
3. For core needle biopsy specimens three to six 18 gauge cores should be collected.
If more than 1 biopsy is planned to be taken from one lesion, the lesion should
be large enough to permit successive biopsies preferably =1 cm apart.
9. At least 4 weeks must have elapsed from any prior major surgery. The following
procedures are not considered major surgical procedure:
1. Obtaining the pre-treatment biopsy 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
10. Laboratory values at screening must be:
a. Adequate 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 CKD-EPI (Chronic
Kidney Disease Epidemiology Collaboration), Cockcroft-Gault, or Modification of Diet
in Renal Disease (MDRD) glomerular filtration rate estimation c. Adequate coagulation:
iv. INR must be <1.5, unless on therapeutic anticoagulants v. PT and activated partial
thromboplastin time (aPTT) =1.6 x ULN unless therapeutically warranted d. Aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) <3x ULN e. Bilirubin <1.5 x
ULN, except for patients with a known familial hyperbilirubinemia (such as e.g.,
Gilbert syndrome). For patients with documented Gilbert's syndrome
(Gilbert-Meulengracht syndrome) total bilirubin <3 x ULN is acceptable) f. Potassium,
calcium, and magnesium that are >0.9 of LLN and =1.1 of ULN. Supplementation is
allowed for potassium, calcium and magnesium to reach these values
11. A woman of childbearing potential (WOCBP) should only be included after a confirmed
menstrual period and a negative serum pregnancy test at Screening.
a. Where ovarian activity is being suppressed by chemotherapy, confirmation of
non-pregnancy by menstrual period is not required
12. A female patient is eligible to participate if she is not pregnant, not breastfeeding
(for 12 months following last dose of rituximab), and at least one of the following
conditions applies:
1. Not a woman of child bearing potential (WOCBP)
2. A WOCBP who agrees to follow the contraceptive guidance during the treatment
period and for at least 3 months after the last dose of MP0310 and 12 months
after the last dose of rituximab, whichever is longer.
13. Men who are not surgically sterilized (and with appropriate post vasectomy
documentation of the absence of sperm in the ejaculate) and who are partners of WOCBP
must be willing to use adequate contraception as detailed in Section 15.7 from the
Screening visit, during the treatment period, and for at least 3 months after the last
MP0310 IMP administration and refrain from donating sperm during this period.
14. Covered by healthcare insurance (if applicable, in accordance with local regulations)
Exclusion criteria
1. Known hypersensitivity to the following excipients that are used for formulation of
MP0310:
a. L-histidine, L-histidine hydrochloride, D-mannitol and polysorbate 20
2. Patients with autoimmune diseases, except auto-immune endocrinopathies that are stable
with hormone replacement therapy
3. Patients with inflammatory diseases such as arthritis, colitis, liver fibrosis,
cirrhosis, interstitial fibrosis, or COPD (chronic obstructive pulmonary disease; that
may have elevated tissue FAP expression) unless approved after consultation by the
Medical Monitor (MM).
4. Concurrent enrollment in another clinical study, unless it is an observational (non
interventional) clinical study for the duration of this study or the follow-up period
of an interventional study
5. Patient was previously treated in this study
6. Serious illness or concomitant non-oncological disease considered by the Investigator
to be incompatible with participating in the protocol
7. Bisphosphonate therapy for symptomatic hypercalcemia
a. Patients on stable dose of bisphosphonate therapy or receptor activator of nuclear
kappa-B ligand (RANKL)-therapy for more than 8 weeks prior to first scheduled dose of
MP0310 for other reasons (e.g., bone metastasis or osteoporosis) are allowed
8. Use of an investigational agent within the past 4 weeks before first MP0310 IMP
administration in this study
9. Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy,
within 3 weeks prior to first MP0310 IMP administration; however, the following are
allowed:
1. Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists or
antagonists for prostate cancer
2. Hormone-replacement therapy or oral contraceptives
3. Palliative radiotherapy for bone metastases 2 weeks prior to first MP0310 IMP
administration
10. Corticosteroid use exceeding 10 mg/day prednisone or equivalent
11. Left ventricular ejection fraction of <50% on echocardiographic exam or multigated
acquisition (MUGA) scan at screening
12. Any 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 the previous 6 months
3. Documented history of congestive heart failure of New York Heart Association >2
criteria
4. Any cardiac arrhythmia that is not well controlled
5. QT corrected (QTc) prolongation > Grade 1 (>480 ms) at screening measured on 2
separate electrocardiograms (ECGs) at least 10 minutes apart
6. Clinically significant valvular heart disease
13. Severe dyspnea, pulmonary dysfunction, or need for continuous supportive oxygen
inhalation
14. Arterial thromboembolic event, stroke, or transient ischemia attack within the past 12
months
15. Patients with known central nervous system (CNS) metastasis that are either untreated
or are treated but are associated with clinical symptoms (e.g., headache,
convulsions). Patients with CNS metastasis that have been treated with radiotherapy
and/or surgery are eligible if they are clinically without symptoms for at least 6
weeks; 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 two weeks.
16. Any active uncontrolled bleeding, or a bleeding diathesis
17. Therapy for active infection needs to be completed at least 7 days prior to the start
of therapy
18. Patients with a known positivity for human immunodeficiency virus (HIV)
19. Patients with 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 antibody to
hepatitis B core antigen antibody test) are eligible.
20. Patients with 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 antibody are eligible only if polymerase chain
reaction (PCR) is negative for HCV RNA.
21. Serious or non-healing wound, skin ulcer, or non-healing bone fracture
22. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the
past 6 months
23. Albumin <2.8 g/dL or <28 g/L, and without albumin transfusion for =7 days prior to
screening
24. Unwilling or unable to follow protocol requirements
25. Any live virus vaccine within 30 days prior to the start of therapy
26. Has had an allogenic tissue/solid organ transplant
27. History of another primary malignancy except for:
1. Malignancy treated with curative intent and with no known active disease =2 years
before the first dose of investigational product and of relatively low potential
risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of 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 enrolled, pending discussion and
approval by the MM
28. Male or female patients of reproductive potential who are not willing to employ
adequate contraception from screening to at least 3 months after the last MP0310 IMP
administration
29. Any condition that, in the opinion of the Investigator, would interfere with
evaluation of the MP0310 IMP or interpretation of the patient's safety or study
results
30. 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
31. Known hypersensitivity or allergy to murine products or any excipients of rituximab
(Part C only)
32. Active, severe infections and/or severely immunocompromised state
33. Contraindication against mandatory prophylactic premedication
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