A phase 1, first-in-human, multicenter, open-label, dose-escalation study to characterize the safety and tolerability of MP0317 in patients with relapsed/refractory advanced solid tumors
- Conditions
- Solid tumors / cancer10027655
- Registration Number
- NL-OMON51895
- Lead Sponsor
- Molecular Partners AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
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:
a. Colorectal cancer
b. Ovarian cancer
c. Endometrial cancer
d. Gastric cancer
e. Pancreatic cancer
f. Anal cancer
g. Cervical cancer
h. Head and neck squamous cell carcinoma (HNSCC)
i. Mesothelioma
j. Prostate cancer
k. Non-small cell lung cancer (NSCLC)
l. Melanoma
m.Urothelial/bladder cancer
n. Microsatellite instability high cancer of any type
o. Cutaneous squamous cell cancer
p. Breast cancer
2. >= 18 years of age on the day of signing informed consent
3. Has signed and dated written informed consent before performing any study
procedure, including screening
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1
5. Anticipated life expectancy >= 12 weeks by Investigator judgement
6. Measurable disease according to Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1
7. 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:
a. 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.
b. 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.
c. For core needle biopsy specimens, at least 3 to 6 cores with an 18-gauge
needle should be collected.
d. 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.
8. Should agree to undergo mandatory paired (pre and on-treatment) skin
biopsies
9. At least 28 days must have elapsed between any prior major surgery and
screening. The following procedures are not considered major:
a. Obtaining the pre-treatment tumor and skin biopsies as per protocol
requirements
b. Placement of a port for central venous access
c. Needle, punch or excisional biopsy of a clinically or radiographically
detected lesion
10. 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
11. Is using high
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:
a. Evidence of poorly controlled arterial hypertension (systolic blood
pressure > 160 mmHg or diastolic blood pressure > 100 mmHg)
b. Myocardial infarction or instable angina pectoris within 6 months before
screening
c. Heart failure (New York Heart Association Class III or IV)
d. Any cardiac arrhythmia that is not well controlled
e. QT corrected (QTc) prolongation >= Grade 2 (> 480 ms) at screening
measured on 2 separate electrocardiograms (ECG) at least 10 minutes apart
f. 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 CNS metastases 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 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 al
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Incidence of dose-limiting toxicities (DLTs)<br /><br>• Type, incidence and severity of adverse events (AEs) and serious adverse<br /><br>events (SAEs) according to the National Cancer Institute Common Terminology<br /><br>Criteria for Adverse Events (NCI CTCAE) v5.0<br /><br>• Changes between screening and post-screening laboratory parameters and vital<br /><br>signs</p><br>
- Secondary Outcome Measures
Name Time Method