Solid tumors / cancer
Conditions
Interventions
For each subject, the assigned dose of MP0317 will be based on the available
cohort as recommended by the dose escalation review committee (DERC).
For the dose-escalation study part on q3w schedule,
Sponsors
Molecular Partners AG
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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: 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 50 mL/min on the basis of Cockcroft-Gault glomerular filtration rate estimation c. Coagulation: i. International normalized ratio (INR) 2.8 g/dL or > 28 g/L, and without albumin transfusion for >= 7 days before screening 11. Is using high
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Incidence of dose-limiting toxicities (DLTs) • Type, incidence and severity of adverse events (AEs) and serious adverse events (SAEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 • Changes between screening and post-screening laboratory parameters and vital signs | — |
Secondary
| Measure | Time frame |
|---|---|
| Secundary endpoints: • Serum concentration-time profiles following first and repeated MP0317 infusions • Determination of PK parameters including (but not limited to) maximum serum concentration (Cmax), time to Cmax (Tmax), minimal serum concentration (Cmin), area under the curve (AUC), total clearance (CL), volume of distribution at steady state (Vss) and half-life (t1/2) • Overall response rate (ORR) based on best overall response (BOR) of complete response (CR) and partial response (PR) locally assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and iRECIST • Disease control rate (DCR) of CR, PR or stable disease (SD) lasting 4 or more weeks following the initiation of MP0317 • Duration of response (DOR) of CR or PR based on RECIST v1.1 and iRECIST, time to progression (TTP) following the initiation of MP0317 • Progression-free survival (PFS) based on RECIST v1.1 and iRECIST • Overall survival (OS) Exploratory endpoints: • Changes in frequency and functionality of B cells, dendritic cells (DC), macrophages and T cell subsets in peripheral blood and tissue biopsies • Assess FAP and CD40 expression and co-localization with MP0317 in tissue biopsies • Changes in cytokines in serum • Changes in soluble FAP (sFAP) and soluble CD40 (sCD40) in serum • Circulating tumor DNA (ctDNA) (safety expansion part only) • Occurrence of anti-drug antibodies (ADAs) • Incidence, titer and time-course of ADAs | — |
Countries
Netherlands
Outcome results
None listed