Overview

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.

Eligibility

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/L
• 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.