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

NCT05098405 | Terminated Phase 1

• 2 other identifiers: MP0317-CP1012020-005516-22
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 4

Brief 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 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.

Conditions

Advanced Malignant Solid Tumor

Keywords

Designed ankyrin repeat protein; DARPin®; fibroblast activation protein; CD40 antigen; advanced malignant solid neoplasm; relapsed malignant solid neoplasm; refractory malignant solid neoplasm

Outcome Measures

Primary Outcomes (4)

• 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

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

• 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

  4 weeks after first study drug administration

• Maximum tolerated dose (MTD)

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

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

• Recommended dose for expansion (RDE)

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

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

Secondary Outcomes (11)

• Serum concentration-time profiles

  4.5 months

• Area under the serum curve (AUC)

  4.5 months

• Total clearance (CL)

  4.5 months

• Volume of distribution at steady state (Vss)

  4.5 months

• Half-life (t1/2)

  4.5 months

Study Arms (2)

Dose-escalation Cohorts (q3w)

EXPERIMENTAL

The 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.

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

Dose-escalation Cohorts (q1w)

EXPERIMENTAL

The 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.

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

Interventions

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).

Dose-escalation Cohorts (q3w)

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).

Dose-escalation Cohorts (q1w)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Molecular Partners AG: lead

Study Sites (4)

Centre Léon Bérard

Lyon, 69373, France

Location

IUCT-O Institut Claudius Régaud

Toulouse, 31059, France

Location

NKI-AvL

Amsterdam, 1066 CX, Netherlands

Location

UMCU

Utrecht, 3584 CW, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 35319751 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2021
• First Posted: October 28, 2021
• Study Start: October 11, 2021
• Primary Completion: January 19, 2024
• Study Completion: January 19, 2024
• Last Updated: January 30, 2025

Record last verified: 2025-01

Locations

NL (2); FR (2)