Clinical Trials /

Study to Investigate the Safety, Blood Levels and Activity of MP0310 (AMG 506) in Patients With Advanced Solid Tumors

NCT04049903

Description:

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

Related Conditions:
  • Anal Carcinoma
  • Bladder Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Mesothelioma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Prostate Carcinoma
  • Skin Squamous Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Investigate the Safety, Blood Levels and Activity of MP0310 in Patients With Advanced Solid Tumors
  • Official Title: A First-In-Human, Single-Arm, Multi-Center, Open-Label, Repeated-Dose, Dose-Escalation Study of MP0310 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: MP0310-CP101
  • SECONDARY ID: 2018-004786-13
  • NCT ID: NCT04049903

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
MP0310MP0310

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
MP0310ExperimentalEnrollment will follow a standard 3 + 3 dose escalation design. Sequential Cohorts of patients will be dosed until the MTD is exceeded, unacceptable toxicity is reached, or until the maximum protocol specified dose is delivered. Up to 12 additional patients in total may be included at selected dose levels (up to 3).
  • MP0310

Eligibility Criteria

        Inclusion Criteria

          -  Advanced solid tumor of one of the following types, treated with at least one line of
             systemic therapy, with no available treatment options: 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

          -  ≥18 years of age

          -  Eastern Cooperative Oncology Group performance status (ECOG; PS) ≤1

          -  Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
             v1.1 criteria

          -  Mandatory paired (pre- and on-treatment) biopsies

          -  Adequate organ function as defined in the protocol

          -  A woman of childbearing potential (WOCBP) should only be included after a confirmed
             menstrual period and a negative serum pregnancy test at Screening.

          -  Female participant is eligible to participate if she is not pregnant, not
             breastfeeding, and at least one of the following conditions applies:

               -  Not a woman of child bearing potential (WOCBP) as defined in the protocol

               -  A WOCBP who agrees to follow the contraceptive guidance as defined in the
                  protocol

          -  Men who are not surgically sterilized and who are partners of WOCBP must be willing to
             use adequate contraception as detailed in the protocol

        Exclusion Criteria

          -  Autoimmune diseases, except auto-immune 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)

          -  Bisphosphonate therapy for symptomatic hypercalcemia

          -  Use of an investigational agent within the past 4 weeks before first MP0310
             administration in this study

          -  Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy,
             within 3 weeks prior to first MP0310 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
                  administration

          -  Corticosteroid use exceeding 10 mg/day prednisone or equivalent

          -  Left ventricular ejection fraction of <50%

          -  Any history or evidence of clinically significant cardiovascular disease as defined in
             the protocol

          -  Severe dyspnea, pulmonary dysfunction, or need for continuous supportive oxygen
             inhalation

          -  Arterial thromboembolic event, stroke, or transient ischemia attack within the past 12
             months

          -  Known central nervous system (CNS) metastasis that are either untreated or are treated
             but are associated with clinical symptoms (e.g., headache, convulsions). Participants
             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; 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 two weeks.

          -  Any active uncontrolled bleeding, or a bleeding diathesis

          -  Patients with a known positivity for human immunodeficiency virus (HIV)

          -  Patients with active hepatitis B (chronic or acute; HBV)

          -  Patients with active hepatitis C (HCV) infection

          -  Serious or non-healing wound, skin ulcer, or non-healing bone fracture

          -  Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the
             past 6 months

          -  Albumin <2.8 g/dL or <28 g/L, and without albumin transfusion for ≥7 days prior to
             screening

          -  Any live virus vaccine within 30 days prior to the start of therapy (Note: Inactivated
             seasonal flu vaccine is acceptable)

          -  Has had 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 the first dose of investigational product and of relatively low potential
                  risk for recurrence

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated carcinoma in situ without evidence of disease

               -  Incidental histologic findings of prostate cancer that, in the opinion of the
                  Investigator, is not deemed to require active therapy

          -  Male or female participants of reproductive potential who are not willing to employ
             adequate contraception from screening to 3 months after the last MP0310 administration
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events (AEs)
Time Frame:From signing of informed consent form (ICF) until 10 weeks following the last dose or start of new anticancer therapy.
Safety Issue:
Description:According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

Secondary Outcome Measures

Measure:Serum concentration - time profiles
Time Frame:24 months
Safety Issue:
Description:Including parameters like maximal serum concentration (Cmax), time at Cmax (Tmax), minimal serum concentration (Cmin)
Measure:Area under the serum concentration-time curve (AUC)
Time Frame:24 months
Safety Issue:
Description:Pharmacokinetic (PK) analysis of MP0310
Measure:Total clearance (CL)
Time Frame:24 months
Safety Issue:
Description:PK analysis of MP0310
Measure:Volume of distribution (Vd), volume at steady state (Vss)
Time Frame:24 months
Safety Issue:
Description:PK analysis of MP0310
Measure:Terminal elimination half-life (t1/2)
Time Frame:24 months
Safety Issue:
Description:PK analysis of MP0310
Measure:Accumulation ratio
Time Frame:24 months
Safety Issue:
Description:PK analysis of MP0310
Measure:Incidence of anti-drug-antibodies
Time Frame:24 months
Safety Issue:
Description:Serum concentration-time profile of anti-drug antibodies
Measure:Objective response rate (ORR)
Time Frame:24 months
Safety Issue:
Description:The proportion of participants with confirmed 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)
Measure:Disease control rate (DCR)
Time Frame:24 months
Safety Issue:
Description:Stable disease lasting 4 or more weeks following the initiation of MP0310
Measure:Duration of response (DoR)
Time Frame:24 months
Safety Issue:
Description:For participants with CR or PR, DOR will be calculated as time from initial response of CR or PR to progressive disease or death.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Molecular Partners AG

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