AzTrials
AzTrials

Advanced Malignant Solid TumorPhase 1NCT05098405

First-in-human Safety and Tolerability of MP0317 in Patients With Relapsed/Refractory Advanced Solid Tumors

A Phase 1 study testing MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q3w regimen) and MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q1w regimen) in people with Advanced Malignant Solid Tumor, run by Molecular Partners AG at 4 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This study is investigating a new experimental therapy, MP0317, a DARPin® drug candidate targeting fibroblast activation protein (FAP) and CD40. Preclinical studies suggest that MP0317 may provide benefit for the treatment of tumors known to express high levels of FAP and for which approved therapies have been… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Malignant Solid Tumor
What is being tested?
MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q3w regimen) and MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q1w regimen)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
4 sitesin 2 countries
Study dates
11 Oct 2021to 19 Jan 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • Colorectal cancer
  • Ovarian cancer
  • Endometrial cancer
  • Gastric cancer
  • Pancreatic cancer
Show all 38Show fewer
  • Anal cancer
  • Cervical cancer
  • Head and neck squamous cell carcinoma (HNSCC)
  • Mesothelioma
  • Prostate cancer
  • Non-small cell lung cancer (NSCLC)
  • Melanoma
  • Urothelial/bladder cancer
  • Microsatellite instability high cancer of any type
  • Cutaneous squamous cell cancer
  • Breast cancer
  • Has signed and dated written informed consent before performing any study procedure, including screening
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1
  • Anticipated life expectancy ≥ 12 weeks by Investigator judgement
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • 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:
  • 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.
  • 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.
  • For core needle biopsy specimens, at least 3 to 6 cores with an 18-gauge needle should be collected.
  • 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.
  • Should agree to undergo mandatory paired (pre and on-treatment) skin biopsies
  • At least 28 days must have elapsed between any prior major surgery and screening. The following procedures are not considered major:
  • Obtaining the pre-treatment tumor and skin biopsies as per protocol requirements
  • Placement of a port for central venous access
  • Needle, punch or excisional biopsy of a clinically or radiographically detected lesion
  • Laboratory parameters at screening:
  • 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
  • Is using highly effective contraception, for females of childbearing potential (FCBP) and for men, as follows:
  • 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.

Who cannot join

  • Known hypersensitivity to excipients used in the MP0317 formulation
  • Autoimmune diseases, except autoimmune endocrinopathies that are stable with hormone replacement therapy
  • 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
  • Serious illness or concomitant non-oncological disease considered by the Investigator to be incompatible with participating in the protocol
  • Left ventricular ejection fraction of < 50% on echocardiographic exam or multi-gated acquisition (MUGA) scan at screening
  • History or evidence of clinically significant cardiovascular disease defined as at least one of the following criteria:
Show all 40Show fewer
  • Evidence of poorly controlled arterial hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg)
  • Myocardial infarction or instable angina pectoris within 6 months before screening
  • Heart failure (New York Heart Association Class III or IV)
  • Any cardiac arrhythmia that is not well controlled
  • QT corrected (QTc) prolongation ≥ Grade 2 (> 480 ms) at screening measured on 2 separate electrocardiograms (ECG) at least 10 minutes apart
  • Clinically significant valvular heart disease
  • Severe dyspnea, pulmonary dysfunction or need for continuous supportive oxygen inhalation
  • Arterial thromboembolic event, stroke or transient ischemia attack within 12 months before screening
  • 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.
  • Active uncontrolled bleeding or a bleeding diathesis
  • Therapy for active infection needs to be completed at least 7 days before first study drug administration
  • Known positivity for human immunodeficiency virus (HIV) or history of HIV (HIV testing is not mandatory)
  • 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.
  • 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.
  • Serious or non-healing wound, skin ulcer or non-healing bone fracture
  • Abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months before screening
  • Any vaccines within 28 days before first study drug administration
  • An allogenic tissue/solid organ transplant
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥ 2 years before screening and of relatively low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of residual disease
  • Adequately treated carcinoma in situ without evidence of disease
  • 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
  • Previous treatment with a DARPin® molecule
  • 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
  • Use of an investigational agent within 28 days before first study drug administration
  • Any anticancer treatment, including chemotherapy, hormonal therapy or radiotherapy, within 21 days before first study drug administration; however, the following are allowed:
  • Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists or antagonists
  • Hormone-replacement therapy or oral contraceptives
  • Palliative radiotherapy for bone metastases within 14 days before first study drug administration
  • Continuous corticosteroid use exceeding 10 mg/day prednisone or equivalent
  • 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
  • Unable or unwilling to comply with all study requirements for clinical visits, examinations, tests and procedures
  • 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

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

France2 sites

  • Centre Léon Bérard

    Lyon, 69373

  • IUCT-O Institut Claudius Régaud

    Toulouse, 31059

Other trials in France

Netherlands2 sites

  • NKI-AvL

    Amsterdam, 1066 CX

  • UMCU

    Utrecht, 3584 CW

Other trials in Netherlands

About this study

Official title: 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

This study is investigating a new experimental therapy, MP0317, a DARPin® drug candidate targeting fibroblast activation protein (FAP) and CD40. Preclinical studies suggest that MP0317 may provide benefit for the treatment of tumors known to express high levels of FAP and for which approved therapies have been exhausted. This is the first study of MP0317 in humans and its main purpose is to test its safety and tolerability in patients with advanced solid tumors. This study will also examine the blood levels of MP0317 at several increasing dose levels and a recommended dose for further development will be determined. The recommended dose will be tested in a second part of the study to confirm safety and to further assess the preliminary biologic and anti-tumor activity.

Being tested
MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q3w regimen), MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q1w regimen)
Keywords
Designed ankyrin repeat protein, DARPin®, fibroblast activation protein, CD40 antigen, advanced malignant solid neoplasm, relapsed malignant solid neoplasm, refractory malignant solid neoplasm

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q3w regimen)Drug

    The study will start with dose-escalation cohorts to determine the recommended dose for expansion (RDE) or the maximum tolerated dose (MTD).

    Once the RDE (or MTD) has been determined, a safety expansion cohort will be opened and additional patients will be treated with MP0317 monotherapy at this dose to confirm safety in a larger population.

    Study treatment will be administered every 3 weeks (q3w) as an intravenous (IV) infusion until progressive disease (PD), unacceptable toxicity, withdrawal of consent or other reasons to discontinue treatment occur, whichever comes first. Treatment beyond PD will be allowed as per Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST).

  • MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q1w regimen)Drug

    The study will start with dose-escalation cohorts to determine the recommended dose for expansion (RDE) or the maximum tolerated dose (MTD).

    Once the RDE (or MTD) has been determined, a safety expansion cohort will be opened and additional patients will be treated with MP0317 monotherapy at this dose to confirm safety in a larger population.

    Study treatment will be administered every week (q1w) as an intravenous (IV) infusion until progressive disease (PD), unacceptable toxicity, withdrawal of consent or other reasons to discontinue treatment occur, whichever comes first. Treatment beyond PD will be allowed as per Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST).

Study groups in NCT05098405
Study groupRoleWhat they receive
Dose-escalation Cohorts (q3w)ExperimentalThe starting dose is 0.03 mg/kg every 3 weeks (q3w) and up to 6 dose levels are planned. Study treatment will be administered as an intravenous (IV) infusion until progressive disease (PD), unacceptable toxicity, withdrawal of consent or other reasons to discontinue treatment occur, whichever comes first.
Receives: Drug: MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q3w regimen)
Dose-escalation Cohorts (q1w)ExperimentalThe starting dose is 0,5 mg/kg every week (q1w) and up to 3 dose levels are planned. Study treatment will be administered as an intravenous (IV) infusion until progressive disease (PD), unacceptable toxicity, withdrawal of consent or other reasons to discontinue treatment occur, whichever comes first.
Receives: Drug: MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q1w regimen)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Type, incidence and severity of AEs and serious adverse events (SAEs)

    According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    Measured: From first study drug administration and until 28 days after the last study drug administration or end of study (EOS)

  2. Incidence of dose-limiting toxicities (DLTs)

    DLTs will be reviewed as a subset of AEs that occur within 4 weeks after first study drug administration

    Measured: 4 weeks after first study drug administration

  3. Maximum tolerated dose (MTD)

    Based on occurrence of DLTs within an adaptive study design following Bayesian Logistic Regression Model (BLRM)

    Measured: From first study drug administration and until 28 days after the last study drug administration or end of study (EOS)

  4. Recommended dose for expansion (RDE)

    Based on incidence and nature of DLTs, and incidence, nature, and severity of AEs and SAEs

    Measured: From first study drug administration and until 28 days after the last study drug administration or end of study (EOS)

Secondary outcomes (11)

  1. Serum concentration-time profiles

    Including parameters like maximum serum concentration (Cmax), time at Cmax (Tmax), minimal serum concentration (Cmin)

    Measured: 4.5 months

  2. Area under the serum curve (AUC)

    Pharmacokinetic (PK) analysis of MP0317

    Measured: 4.5 months

  3. Total clearance (CL)

    PK analysis of MP0317

    Measured: 4.5 months

  4. Volume of distribution at steady state (Vss)

    PK analysis of MP0317

    Measured: 4.5 months

  5. Half-life (t1/2)

    PK analysis of MP0317

    Measured: 4.5 months

  6. Overall response rate (ORR)

    Proportion of participants with complete response (CR) and partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST)

    Measured: 4.5 months

  7. Disease control rate (DCR)

    Best overall response (BOR) of CR, PR or stable disease (SD) lasting 4 or more weeks following first study drug administration

    Measured: 4.5 months

  8. Duration of response (DOR) of CR or PR

    For participants with CR or PR, DOR will be calculated as the time from CR or PR to progressive disease (PD) or death.

    Measured: 4.5 months

  9. Time to progression (TTP)

    Time from first study drug administration to PD

    Measured: 4.5 months

  10. Progression-free survival (PFS)

    Time from first study drug administration to PD or death

    Measured: 4.5 months

  11. Overall survival (OS)

    Time from first study drug administration to death of any cause

    Measured: 12 months; including 4.5 months survival follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2021
  2. Study start11 Oct 2021
  3. Primary completion19 Jan 2024
  4. Study completion19 Jan 2024

Why it stopped: After completion of the dose-escalation part of the study, the safety profile of MP0317 in monotherapy is considered adequately characterized in the dose-escalation part of the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05098405
Sponsor's protocol ID
MP0317-CP101
Other IDs
2020-005516-22
Status last verified
Jan 2025
First submitted
30 Sep 2021
Last updated
30 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Steeghs N, Gomez-Roca C, Korakis I, Gort E, De Winter H, Stojcheva N, Stavropoulou V, Krieg J, Baverel P, Fernandez E, Florescu AM, Hoenig L, Sanderson MP, Kirkin V, Legenne P, Cassier PA. Tumor-localized CD40 agonism with MP0317, a FAP x CD40 DARPin, reprograms the tumor microenvironment in patients with advanced solid tumors: an open-label, nonrandomized, dose-escalation phase 1 study. Nat Cancer. 2026 May;7(5):810-822. doi: 10.1038/s43018-026-01150-1. Epub 2026 May 1.

    PubMed 42067655

  • Rigamonti N, Veitonmaki N, Domke C, Barsin S, Jetzer S, Abdelmotaleb O, Bessey R, Lekishvili T, Malvezzi F, Gachechiladze M, Behe M, Levitsky V, Trail PA. A Multispecific Anti-CD40 DARPin Construct Induces Tumor-Selective CD40 Activation and Tumor Regression. Cancer Immunol Res. 2022 May 3;10(5):626-640. doi: 10.1158/2326-6066.CIR-21-0553.

    PubMed 35319751

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q3w regimen) and MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q1w regimen) in people with Advanced Malignant Solid Tumor, run by Molecular Partners AG at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in France, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: After completion of the dose-escalation part of the study, the safety profile of MP0317 in monotherapy is considered adequately characterized in the dose-escalation part of the study.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Type, incidence and severity of AEs and serious adverse events (SAEs) (time frame: From first study drug administration and until 28 days after the last study drug administration or end of study (EOS)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05098405, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in