Study to Investigate the Safety, Blood Levels and Activity of MP0310 in Patients With Advanced Solid Tumors

NCT04049903 | Completed Phase 1

• 2 other identifiers: MP0310-CP1012018-004786-13
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

Brief Summary

To evaluate the safety and tolerability of MP0310, a DARPin® therapeutic candidate for tumor targeted activation of T cells, in patients with advanced solid tumors

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Incidence of Adverse Events (AEs)

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

  From signing of informed consent form (ICF) until 10 weeks following the last dose or start of new anticancer therapy.

• Incidence of dose-limiting toxicities (DLTs)

  Dose-limiting toxicities will be reviewed as a subset of AEs that occur within the first 21 days of dosing and meet the protocol-specified criteria.

  First 21 days of dosing.

• Maximum tolerated dose (MTD) or a tolerated dose below MTD (if MTD is not reached)

  Based on occurrence of DLTs within a 3+3 clinical trial design

  From signing of ICF until 10 weeks following the last dose or start of new anticancer therapy.

• Recommended expansion dose (RED)

  Based on incidence and nature of DLTs, and incidence, nature, and severity of AEs and serious adverse events (SAEs)

  From signing of ICF until 10 weeks following the last dose or start of new anticancer therapy.

Secondary Outcomes (10)

• Serum concentration - time profiles

  24 months

• Area under the serum concentration-time curve (AUC)

  24 months

• Total clearance (CL)

  24 months

• Volume of distribution (Vd), volume at steady state (Vss)

  24 months

• Terminal elimination half-life (t1/2)

  24 months

Study Arms (3)

MP0310 Part A

EXPERIMENTAL

Enrollment will follow a standard 3 + 3 dose escalation design. Sequential Cohorts of patients will be dosed until the MTD or unacceptable toxicity is reached. Up to 12 additional patients in total may be included at selected dose levels (up to 3).

Drug: MP0310

MP0310 Part B

EXPERIMENTAL

weekly schedule, at least 3 and up to 24 patients evaluable for DLT assessment will be enrolled (1 to 4 cohorts with 3 to 6 patients each (3 initial plus up to 3 backfill patients)).

Drug: MP0310

MP0310 Part C

EXPERIMENTAL

q3w schedule implementing B-cell depletion, at least 3 and up to 12 patients evaluable for DLT assessment will be enrolled (1 to 2 cohorts with 3 to 6 patients each (3 initial plus up to 3 backfill patients)).

Drug: MP0310

Interventions

MP0310 DRUG

MP0310 will be examined for safety, tolerability, PK, and PD activity in subjects with advanced solid tumors

MP0310 Part A; MP0310 Part B; MP0310 Part C

Eligibility Criteria

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

You may qualify if:

• 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,
• Patients have to be willing to comply with study procedures
• ≥18 years of age
• Mentally competent, able to understand and willing to sign the ICF
• Eastern Cooperative Oncology Group performance status (ECOG; PS) ≤1
• Anticipated life expectancy ≥12 weeks by Investigator judgment
• The disease is measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
• Mandatory paired pre- and on-treatment biopsies - preferably from the same lesion - are required as follows:
• 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
• 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
• 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.
• At least 4 weeks must have elapsed from any prior major surgery. The following procedures are not considered major surgical procedure:
• Obtaining the pre-treatment biopsy as per protocol requirements
• Placement of a port for central venous access
• Needle, punch or excisional biopsy of a clinically or radiographically detected lesion

You may not qualify if:

• Known hypersensitivity to the following excipients that are used for formulation of MP0310:
• a. L-histidine, L-histidine hydrochloride, D-mannitol and polysorbate 20
• Patients with autoimmune diseases, except auto-immune endocrinopathies that are stable with hormone replacement therapy
• 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).
• 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
• Patient was previously treated in this study
• Serious illness or concomitant non-oncological disease considered by the Investigator to be incompatible with participating in the protocol
• 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
• Use of an investigational agent within the past 4 weeks before first MP0310 IMP administration in this study
• Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to first MP0310 IMP administration; however, the following are allowed:
• Hormonal therapy with gonadotropin-releasing hormone (GnRH) agonists or antagonists for prostate cancer
• Hormone-replacement therapy or oral contraceptives
• Palliative radiotherapy for bone metastases 2 weeks prior to first MP0310 IMP administration
• Corticosteroid use exceeding 10 mg/day prednisone or equivalent

Sponsors & Collaborators

• Molecular Partners AG: lead

Study Sites (3)

Centre Léon Bérard

Lyon, 69008, France

Location

Institut Claudius Regaud; Institut Universitaire du Cancer Toulouse Oncopole (IUCT-O)

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

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: August 5, 2019
• First Posted: August 8, 2019
• Study Start: September 2, 2019
• Primary Completion: June 27, 2022
• Study Completion: December 21, 2022
• Last Updated: December 22, 2022

Record last verified: 2022-12

Locations

FR (3)