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

ID#: NCT04244552

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 1

Recruitment Status: Recruiting

Start Date: February 11, 2020

End Date: March 01, 2025

Contact Information:
Nick Higgins
Summary: ATRC-101-A01 is a Phase 1b, open-label dose escalation trial of ATRC-101, an engineered fully human immunoglobulin G, subclass 1 (IgG1) antibody derived from a naturally occurring human antibody. The safety, tolerability, PK, and biological activity of ATRC-101 will be characterized when administered every two weeks (Q2W) or every 3 weeks (Q3W) as a monotherapy or in combination with other anticancer agents.

Inclusion Criteria:

- Confirmed diagnosis of:

1. For the monotherapy cohorts: Metastatic or unresectable BC, NSCLC, CRC, 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.

2. For the pembrolizumab combination therapy cohort: Metastatic or unresectable NSCLC, CRC (only MSI-H or dMMR), melanoma (with the exception of uveal melanoma), HCC, HNSCC, ESCC, or UC with prior or ongoing pembrolizumab treatment and have progressed or have achieved stable disease and who, in the judgment of their treating physicians, could benefit from the addition of ATRC-101 to improve or maintain their response.

1. Individuals with BRAF mutant melanoma must have received BRAF inhibitors alone or in combination with a MEK inhibitor, if indicated

2. Individuals with NSCLC should have received platinum-based therapy unless contraindicated

- Measurable disease based on RECIST v1.1, as assessed by the local site investigator/radiologist. Lesions situated in an area treated with radiation or other loco-regional therapy are considered measurable only if the progression has been demonstrated in such lesions following loco-regional therapy.

- 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 as defined by the following laboratory parameters:

- Absolute neutrophil count (ANC) ≥ 1000/µL

- Absolute lymphocyte count (ALC) ≥ 500/ µL

- Platelet count ≥ 75,000/µL

- Hemoglobin ≥ 9.0 g/dL

- PT/INR, aPTT ≤ 1.5 x ULN unless participant is receiving a stable dose of therapeutic anticoagulation

- Albumin ≥ 3.0 g/dL

- Creatinine clearance or eGFR ≥ 30 mL/min as estimated by the Cockcroft-Gault equation

- AST/ALT ≤ 2 x ULN. If documented liver metastases, then ≤ 5X ULN

- Bilirubin ≤ 2 x ULN; or bilirubin ≤ 3 x ULN if due to Gilbert's or Crigler-Najjar disease

- 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. If fewer than 20 unstained slides are available, a discussion with the Medical Monitor is required prior to enrollment. If an archived sample is not available, participant must have a tumor that is amenable to biopsy without unacceptable risk of a major procedural complication and consent to have a tumor biopsy. Tumor lesions used for biopsy should not be lesions used as RECIST 1.1 target lesions unless there are no other lesions suitable for biopsy. If a RECIST target lesion is used for biopsy, the lesion must be ≥ 2cm in longest diameter. a. For the pembrolizumab combination therapy cohort: A biopsy collected within 60 days of the planned first dose of investigational product while the participant is receiving pembrolizumab is acceptable.

- 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

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

Exclusion Criteria:

- Disease that is suitable for local therapy administered with curative intent.

- 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 treat in situ disease.

- Autoimmune disease requiring systemic treatment (e.g., with disease modifying agents, corticosteroids, or immunosuppressive drugs) in the past 2 years. Hormone replacement therapy (e.g., insulin, thyroxine, and replacement-dose hydrocortisone) is not considered systemic treatment.

- 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 (and 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:

1. Grade 2 neuropathy or alopecia

2. For the monotherapy cohorts: 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 with the following exception: a. For the pembrolizumab combination therapy cohort: Pembrolizumab treatment 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 28 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

- History of ≥ Grade 3 infusion-related reaction associated with antibody administration; or:

1. For the monotherapy cohorts: Known allergy/intolerance to ATRC-101 or its excipients

2. For the pembrolizumab combination therapy cohort: Known allergy/intolerance to ATRC 101, pembrolizumab, or their excipients

- 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.

- Receipt of a live vaccine within 30 days of planned Cycle 1-Day

1. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed. Intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed. For the pembrolizumab combination therapy cohort ONLY:

- Experienced ≥ Grade 3 or higher immune related adverse events while on immunotherapy prior to enrollment

- Have not recovered from ≥ Grade 2 immune related adverse events attributed to immunotherapy prior to enrollment.

- NSCLC with epidermal growth factor receptor (EGFR) or anaplastic lymphoma receptor tyrosine kinase (ALK) genomic tumor alterations

- Isolated intracranial relapse

- Interstitial lung disease or active, non-infectious pneumonitis

- Signs and symptoms consistent with clinically significant, decreased pulmonary function: (1) blood saturation oxygen level (SpO2) < 90% at rest on room air; (2) dyspnea at rest (CTCAE ≥ Grade 3) or required supplemental oxygenation within 14 days prior to the planned first dose of investigational product

- Ongoing immune-related toxicity or immune-related toxicity at any time requiring systemic corticosteroids