Clinical Trials /

First-in-Human Dose Escalation Trial of ATRC-101 in Adults With Advanced Solid Malignancies

NCT04244552

Description:

ATRC-101-A01 is a first-in-human, Phase 1b, open-label trial to characterize the safety, tolerability, pharmacokinetics (PK), and biological activity of escalating doses of ATRC-101, an engineered, fully human immunoglobulin G, subclass 1 (IgG1) antibody derived from a naturally-occurring human antibody.

Related Conditions:
  • Acral Lentiginous Melanoma
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-Human Dose Escalation Trial of ATRC-101 in Adults With Advanced Solid Malignancies
  • Official Title: A First-in-Human Phase 1b Dose Escalation Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Biological Activity of ATRC-101 in Adults With Advanced Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: ATRC-101-A01
  • NCT ID: NCT04244552

Conditions

  • Breast Cancer
  • Colorectal Cancer
  • Ovarian Cancer
  • Non Small Cell Lung Cancer
  • Acral Lentiginous Melanoma

Interventions

DrugSynonymsArms
ATRC-101ATRC-101 Dose Escalation

Purpose

ATRC-101-A01 is a first-in-human, Phase 1b, open-label trial to characterize the safety, tolerability, pharmacokinetics (PK), and biological activity of escalating doses of ATRC-101, an engineered, fully human immunoglobulin G, subclass 1 (IgG1) antibody derived from a naturally-occurring human antibody.

Trial Arms

NameTypeDescriptionInterventions
ATRC-101 Dose EscalationExperimental
  • ATRC-101

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of metastatic or unresectable breast cancer, NSCLC, colorectal
             cancer, ovarian cancer, or acral melanoma that is refractory to standard therapy or
             for which no standard therapy exists. Participants who are considered intolerant of or
             ineligible for standard therapy(ies), as well as participants who have been offered
             but refused standard therapy(ies), may also be eligible.

          -  Measurable disease based on RECIST v1.1

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Adequate organ and marrow function (i.e. without chronic, ongoing growth factor or
             transfusion support) at Screening

          -  Available representative tumor specimens in paraffin blocks (preferred) or ≥ 20
             unstained slides, with an associated pathology report, obtained after last systemic
             anti-cancer therapy and within 60 days prior to the planned first dose of
             investigational product.

          -  Women of childbearing potential (WOCBP) and fertile males with partners who are WOCBP
             must use highly effective contraception (per CTFG 2014) from first dose and through 90
             days after final dose of investigational product

          -  Willing and able to provide written informed consent and able to comply with all trial
             procedures.

        Exclusion Criteria:

          -  Malignant disease other than the malignancy to be investigated in this trial within
             the last 5 years with the exception of basal or squamous cell carcinoma of the skin OR
             curatively treated in situ disease.

          -  Primary immunodeficiency affecting cellular immunity (2017 IUIS Classification)

          -  Active autoimmune disease with the exception of Type I Diabetes Mellitus,
             hypothyroidism requiring hormone replacement only, an autoimmune dermatologic
             condition that is managed without systemic therapy, or autoimmune arthritis that is
             managed without systemic therapy

          -  Active or prior paraneoplastic neurologic disorder of the central nervous system (CNS)

          -  Prior allograft

          -  Clinically significant cardiovascular disease, e.g., cerebral vascular accident/stroke
             or myocardial infarction, within 6 months prior to the first dose of investigational
             product, unstable angina, congestive heart failure (New York Heart Association ≥ Class
             III), or unstable cardiac arrhythmia requiring medication

          -  Presence of active, symptomatic, or untreated CNS metastasis; or CNS metastasis that
             requires local directed therapy or increasing doses of corticosteroids within the 2
             weeks prior to the planned first dose of investigational product. Individuals with
             treated and/or asymptomatic CNS disease may be enrolled if neurologically stable over
             the prior 2 weeks (after consultation with the Medical Monitor)

          -  HIV infection with an AIDS-defining opportunistic infection within the past 12 months
             or with a CD4+ T cell count <350/µL

          -  Hepatitis B surface antigen (HBsAg) positive OR anti-Hepatitis B core (anti-HBc)
             positive and HBV viral load above the lower limit of quantification

          -  Hepatitis C antibody positive with HCV viral load greater than or equal to the lower
             limit of quantification

          -  Infection requiring intravenous antibacterial, antiviral, or antifungal therapy within
             2 weeks prior to the planned first dose of investigational product

          -  Ongoing ≥ Grade 2 toxicity(ies) due to a previously administered anticancer agent with
             the following exceptions:

               -  Grade 2 neuropathy or alopecia

               -  Grade 2 immune-related endocrinopathy attributed to a checkpoint inhibitor and
                  controlled with hormone replacement alone

          -  Treatment with biological agents (including monoclonal antibodies) within 28 days of
             the planned first dose of investigational product

          -  Treatment with radiation, chemotherapy or anticancer small molecule therapy within 14
             days or 5 half-lives (whichever is longer) prior to the planned first dose of
             investigational product. Treatment with nitrosoureas or mitomycin C require a 42-day
             washout prior to the planned first dose of investigational product

          -  Receipt of any investigational drug or device not otherwise specified above within 14
             days or 5 half-lives (whichever is longer) prior to the planned first dose of
             investigational product

          -  Pregnant or breastfeeding; negative pregnancy status in WOCBP must be confirmed by
             serum pregnancy test at Screening

          -  Known allergy/intolerance to ATRC-101 or its excipients; or history of ≥ Grade 3
             infusion reaction associated with antibody administration

          -  Major surgery or significant traumatic injury occurring within 28 days prior to the
             planned first dose of investigational product. If major surgery occurred > 28 days
             prior to Cycle 1-Day 1, individual must have recovered adequately from the toxicity
             and/or complications from the intervention prior to Cycle 1-Day 1

          -  Prior treatment with ATRC-101

          -  Intercurrent illness that is either life-threatening or of clinical significance such
             that it might limit compliance with trial requirements, or in the Investigator's
             assessment would place the participant at an unacceptable risk for participation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of DLTs, treatment emergent adverse events (TEAEs), and changes in safety parameters
Time Frame:24 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Maximum plasma concentration (Cmax) of ATRC-101
Time Frame:24 months
Safety Issue:
Description:
Measure:Elimination half-life (t1/2) of ATRC-101
Time Frame:24 months
Safety Issue:
Description:
Measure:Area under the plasma concentration-time curve from zero to the last measurable concentration [AUC(0-t)] of ATRC-101
Time Frame:24 months
Safety Issue:
Description:
Measure:Incidence of anti-drug antibodies (ADAs) and ATRC-101 neutralizing antibodies
Time Frame:24 months
Safety Issue:
Description:
Measure:Best Overall Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame:24 months
Safety Issue:
Description:
Measure:Enumeration of tumor-infiltrating CD8+ lymphocytes (TILs) in tumor biopsy specimens at baseline and during treatment
Time Frame:24 months
Safety Issue:
Description:
Measure:Distribution of tumor-infiltrating CD8+ lymphocytes (TILs) in tumor biopsy specimens at baseline and during treatment
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Atreca, Inc.

Last Updated

January 24, 2020