A Phase I Multicentre, Open-label, Dose Escalation Study to Determine the Safety and Preliminary Efficacy of MBS8(1V270) Administered Intravenously to Cancer Patients With Advanced Solid Tumours

MonTa Biosciences ApS5 sites in 2 countries106 target enrollmentApril 12, 2021

ConditionsAdvanced Solid Tumor

InterventionsMBS8(1V270)MBS8(1V270) and pembrolizumab combination

DrugsMBS8(1V270)

Overview

Phase: Phase 1
Intervention: MBS8(1V270)
Conditions: Advanced Solid Tumor
Sponsor: MonTa Biosciences ApS
Enrollment: 106
Locations: 5
Primary Endpoint: Adverse events
Status: Recruiting
Last Updated: 2 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The Phase I trial is evaluating safety, tolerability, pharmacokinetics and preliminary efficacy of MBS8(1V270) in subjects with advanced solid tumours. The trial is designed to provide data for further clinical development of MBS8(1V270)

Detailed Description

This is a prospective, open-label, single arm, multinational, multicenter Phase I trial in subjects with advanced solid tumors. The trial consists of two stages: Stage I is a dose escalation stage which will include up to eight cohorts with escalating doses of MBS8(1V270) to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Stage II is an expansion phase in which safety and tolerability of MBS8(1V270) will be assessed at the recommended phase 2 dose established in Stage I of the trial. Stage II comprices two cohorts: One cohort in which MBS8(1V270) will be evaluated in combination with pembrolizumab (Keytruda) in cutaneous melanoma patients with acquired resistance to PD-1 therapy; and one cohort in which MBS8(1V270) will be evaluated as monotherapy in uveal melanoma patients previously treated with T-cell engagers. The dose-escalation in stage 1 is based on the 1+2 design for the first cohort and on the 3+3 design for the following cohorts. The investigational medicinal product is a TLR7 agonist and will be administered intravenously by infusion. Subjects will be treated in cycles. Plasma cytokine levels will be assessed, and tumor biopsies will be taken and evaluated. Radiological tumor assessment by MRI or CT will be performed. Safety will be evaluated by the incidence of adverse events (AEs), serious adverse events (SAEs), DLTs, and use of concomitant medications. Anti-tumor activity of MBS8(1V270) will be evaluated via imaging using RECIST and iRECIST criteria, with iRECIST being the leading tumor evaluation criteria.

Registry

clinicaltrials.gov

Start Date

April 12, 2021

End Date

June 1, 2027

Last Updated

2 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

MonTa Biosciences ApS

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Stage I Inclusion Criteria
•Male or female aged ≥18 years.
•Diagnosis of a histologically or cytologically confirmed solid tumour that was advanced and with progression. No standard treatment existed, or the participant refused standard treatment. Experimental immunotherapy appeared as a feasible exploratory treatment option as per Investigator's assessment.
•Tumour lesion(s) accessible to serial biopsies.
•Was willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and tumour biopsies. Mandatory Baseline and on-treatment tumour biopsies were required. However, a biopsy may have been omitted if the procedure was deemed medically unsafe or not feasible, based on the Investigator's clinical judgment and after discussion with the Medical Monitor (or Sponsor's designee).
•Measurable disease according to RECIST v1.
•Previously irradiated lesions were measurable if subsequent progression was documented.
•Eastern Cooperative Oncology Group (ECOG) performance status 0 to
•Life expectancy \>3 months as assessed by the Investigator.
•Adequate bone marrow, cardiopulmonary, renal and hepatic functions:

Exclusion Criteria

•Have had biologic, hormonal, anti-neoplastic chemotherapy, or radiation therapy within 4 weeks prior to Screening (6 weeks required for nitrosourea or mitomycin) except for medications with half-lives \<5.5 days.
•Metastatic disease that involved major airways or blood vessels or centrally located mediastinal tumour masses of large volume with close relation to the major airways, where tumour necrosis may have caused perforation or severe bleeding episodes. Primary or metastatic intestinal disease in situ where tumour necrosis may have caused gastrointestinal perforation.
•Use of investigational agent in the 4 weeks or 5 half-lives prior to the first dose of MBS8(1V270), whichever was shortest.
•Major surgical procedure within 14 days prior to the first dose of trial treatment.
•Had a history of another primary malignancy, except for:
•Malignancy treated with curative intent and with no known active disease within 2 years prior to the first dose of MBS8(1V270)
•Adequately treated non-invasive basal skin cancer or squamous cell skin carcinoma
•Adequately treated uterine cervical cancer Stage 1B or less.
•Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids \[\>10 mg prednisone per day or equivalent, except topical or inhaled\] cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-IL-6 receptor agents, and anti-tumour necrosis factor \[TNF\]α agents) within 2 weeks prior to initiation of trial treatment, or anticipation of need for systemic immunosuppressive medication during trial treatment.
•Treatment with androgen deprivation therapies such as luteinizing hormone-releasing hormone (LHRH) (gonadotropin-releasing hormone \[GnRH\]) agonists within 2 weeks prior to initiation of trial treatment.