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.
For the ATRC-101 monotherapy cohorts, enrollment is restricted to adults with breast cancer
(BC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), ovarian cancer, and acral
melanoma.
For the pembrolizumab combination therapy cohort, enrollment is restricted to adults with
NSCLC, CRC (only MSI-H or dMMR), melanoma (with the exception of uveal melanoma),
hepatocellular carcinoma (HCC), head and neck squamous cell carcinoma (HNSCC), esophageal
squamous cell carcinoma (ESCC), or urothelial carcinoma (UC), that have been treated with
pembrolizumab 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.
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