A Phase 1b Dose Escalation and Expansion Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Biological Activity of ATRC-101 as Monotherapy and in Combination With Other Anticancer Agents in Adults With Advanced Solid Malignancies

  • STATUS
    Recruiting
  • End date
    Mar 23, 2025
  • participants needed
    240
  • sponsor
    Atreca, Inc.
Updated on 23 October 2022
platelet count
cancer
ascites
combination therapy
monoclonal antibodies
measurable disease
breast cancer
growth factor
doxorubicin
BRAF
neutrophil count
pet scan
pembrolizumab
EGFR
chemotherapy regimen
cancer treatment
cancer chemotherapy
antineoplastic
mek inhibitor
ovarian cancer
fallopian tube
platinum-based chemotherapy
peritoneal cancer
cancer of the ovary

Summary

ATRC-101-A01 is a Phase 1b, open-label dose escalation and expansion 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.

Description

For the monotherapy cohorts, including the efficacy expansion cohorts, enrollment is restricted to adults with inoperable, locally advanced or metastatic breast cancer, NSCLC, CRC, ovarian cancer, and acral melanoma, which are all tumor types that have demonstrated ATRC-101 immunoreactivity on at least 50% of tested commercially procured archival specimens.

For the pembrolizumab combination therapy cohort, enrollment is restricted to adults with inoperable, locally advanced or metastatic NSCLC, CRC (only MSI-H or dMMR), melanoma (with the exception of uveal melanoma), HCC, HNSCC, ESCC, UC or TNBC, that have been treated with anti-PD-1 or anti-PD-L1 therapy and have progressed radiographically or have achieved stable disease for a minimum of two months and who, in the judgment of their treating physicians, could benefit from a combination of ATRC 101 and pembrolizumab.

For the PLD combination therapy cohort, enrollment is restricted to adult females with inoperable, locally advanced or metastatic high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer that is platinum resistant, defined as progression during or within 6 months of the last dose of platinum-based chemotherapy OR breast cancer that is refractory to other standard therapies.

For target-enriched expansion cohorts, enrollment will be limited to participants with pretreatment tumor biopsies demonstrating ATRC-101 target expression above a predefined threshold by IHC at a central laboratory.

Details
Condition Breast Cancer, Colorectal Cancer, Ovarian Cancer, Non-Small Cell Lung Cancer, Acral Lentiginous Melanoma, Head and Neck Squamous Cell Carcinoma, Hepatocellular Carcinoma, Esophageal Squamous Cell Carcinoma, Urothelial Carcinoma, DMMR Colorectal Cancer, MSI-H Colorectal Cancer, Melanoma, Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Resistant Fallopian Tube Carcinoma, Platinum-Resistant Epithelial Ovarian Cancer, Triple Negative Breast Cancer
Treatment Pembrolizumab, Pegylated Liposomal Doxorubicin (PLD), ATRC-101
Clinical Study IdentifierNCT04244552
SponsorAtreca, Inc.
Last Modified on23 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Confirmed diagnosis of
For the monotherapy cohorts: Inoperable, locally advanced or metastatic breast cancer, 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
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
For the pembrolizumab combination therapy cohort: Inoperable, locally advanced or metastatic NSCLC, CRC (only MSI-H or dMMR), melanoma (with the exception of uveal melanoma), HCC, HNSCC, ESCC,UC, or TNBC with prior or ongoing anti-PD-1 or anti-PD-L1 treatment and have progressed radiographically or have achieved stable disease for a minimum of two months and who, in the judgment of their treating physicians, could benefit from a combination of ATRC-101 and pembrolizumab . The anti-PD-1/anti-PD-L1 therapy must be FDA approved for their cancer indication at the time of screening. Patients with the tumor types eligible for monotherapy that are TMB-H, MSI-H or dMMR and have had an unsatisfactory response to anti-PD-1/anti-PD-L1 therapy may enroll for the pembrolizumab combination, and additional indications that have been identified as ATRC-101 target positive and are FDA approved for pembrolizumab may be added following discussion with the study Medical Monitor
Individuals with BRAF mutant melanoma must have received BRAF inhibitors alone or in combination with a MEK inhibitor, if indicated
Individuals with NSCLC should have received platinum-based therapy unless contraindicated
For the PLD combination therapy cohort: Inoperable, locally advanced or metastatic
high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal
cancer that is platinum resistant, defined as progression during or within 6
Adequate organ and marrow function (i.e., without chronic, ongoing growth factor or transfusion support) at Screening as defined by the following laboratory parameters via central laboratory results
months of the last dose of platinum-based chemotherapy OR breast cancer that
Absolute neutrophil count (ANC)
is refractory to other standard therapies
Measurable disease based on RECIST 1.1, as assessed by the local site investigator/radiologist. As per RECIST, lesions situated in an area treated with radiation or other loco-regional therapy are considered measurable only if progression has been demonstrated in such lesions following loco-regional therapy
For monotherapy and pembrolizumab combination therapy cohorts: ≥ 1000/µL
For PLD combination therapy cohort: ≥ 1500/µL
Platelet count ≥ 75,000/µL
Bilirubin
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
Willing and able to provide written informed consent and able to comply with all trial procedures
For monotherapy and pembrolizumab combination therapy cohorts: ≤ 2 x ULN; or bilirubin ≤ 3 x ULN if due to Gilbert's or Crigler-Najjar disease
For PLD combination therapy cohort: ≤ ULN
Available representative tumor specimens in paraffin blocks (preferred) or ≥ 20
unstained slides (serial sections), with an associated pathology report
obtained after last systemic anticancer therapy and within 60 days prior to
the planned first dose of investigational product (Cycle 1-Day 1). 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 ≥ 2 cm in longest
diameter. Fine-needle aspirates, cell pellets from pleural effusions, ascites
and bone metastases are not acceptable
For target-enriched expansion cohorts, enrollment will be limited to participants with pretreatment tumor biopsies demonstrating ATRC-101 target expression above a predefined threshold by IHC at a central laboratory
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 anti-PD-1/anti-PD-L1 therapy 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

Exclusion Criteria

Active or prior paraneoplastic neurologic disorder of the central nervous system (CNS)
Grade 2 neuropathy or alopecia
Disease that is suitable for local therapy administered with curative intent
Prior treatment with ATRC-101
For the PLD Combination Therapy Cohort
For the pembrolizumab combination therapy cohort ONLY
For the PLD combination therapy cohort
Prior treatment with PLD
Individuals who meet any of the following criteria are not eligible to participate in this
trial
a. malignancies previously treated with curative intent with a 5-year OS rate >90%
Isolated intracranial relapse
(consultation with the Medical Monitor is required prior to enrollment)
Interstitial lung disease or active, non-infectious pneumonitis
Malignant disease other than the malignancy to be investigated in this trial within
Prior mediastinal irradiation > 3500 cGY
the last 5 years with the exception of
considered systemic treatment for the autoimmune disease
Autoimmune disease requiring systemic treatment (e.g., with disease modifying agents
Prior allogenic hematopoietic or solid organ transplant, including allogeneic cellular
corticosteroids, or immunosuppressive drugs) in the past 2 years. Hormone replacement
therapy (e.g., allogeneic chimeric antigen receptor (CAR)-modified T cells)
therapy (e.g., insulin, thyroxine, and replacement-dose hydrocortisone) is not
Allogeneic bone grafts are not exclusionary
or history of leptomeningeal disease
Clinically significant cardiovascular disease, e.g., cerebral vascular accident/stroke
or myocardial infarction, within 6 months prior to first dose of investigational
product, unstable angina, congestive heart failure (New York Heart Association ≥ Class
III), or unstable cardiac arrhythmia requiring medication
Any history of documented congestive heart failure (CHF), arrhythmia, or
uncontrolled hypertension (systolic BP > 200 mmHg or diastolic BP > 100 mmHg)
For the PLD combination therapy cohort ONLY
Left ventricular ejection fraction measure by echocardiography or multigated
radionuclide acquisition (MUGA) below normal limits for the institution
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) provided there is
measurable disease (RECIST 1.1) outside of the CNS and there is no ongoing requirement
for corticosteroids to manage the disease
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 Hepatitis B core antibody (anti-HBc or
HBcAb) 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
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
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 and cytokines)
within 28 days of the planned first dose of investigational product with the following
exception
a.For the pembrolizumab combination therapy cohort: -Anti-PD-1/anti-PD-L1 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 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
Prior treatment with doxorubicin or other anthracycline at cumulative doses
greater than 300mg/m2
Anthracycline equivalent doses: 1 mg Doxorubicin = 1.8 mg Epirubicin = 0.3 mg
Mitoxantrone = 0.25 mg Idarubicin
Anthracyclines or anti-HER2 agents, if last dose was administered < 1 year before
enrollment
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
For the monotherapy cohorts: Known allergy/intolerance to ATRC-101 or its
excipients
For the pembrolizumab combination therapy cohort: Known allergy/intolerance to
ATRC-101, anti-PD-1 or anti-PD-L1, , or their excipients
For the PLD combination therapy cohort: Known allergy/intolerance to ATRC-101
doxorubicin, or to the excipients of ATRC-101 or PLD
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
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
Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent
drainage procedures is exclusionary
Receipt of a live, attenuated vaccine within 28 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
Replication-incompetent viral, mRNA, subunit, conjugate, and toxoid vaccines are
allowed
COVID-19 (SARS-CoV-2) pandemic consideration: The COVID-19 vaccination should not be
delayed; however, caution should be exercised when combining vaccination with cancer
therapy, particularly immunotherapy. The COVID-19 vaccines can cause transient
lymphadenopathy and potentially impact assessment of disease burden during screening
and/or on-study. To allow correct interpretation and reduce equivocal findings
investigators should discuss with the participant appropriate timing and selection of
anatomic site of vaccination (alternative) with respect to imaging scans (MRI or CT)
Screening scans should be acquired before the first dose of a COVID-19 vaccine or 4-6
weeks after the second dose of the vaccine. Because cancer patients are considered
vulnerable population, after COVID-19 vaccination there is also a potential for
heightened immune related adverse events including CRS. Investigators should use
judgement when evaluating and managing potentially overlapping adverse events and in
establishing causality with the study treatment (Schönrich and Raftery 2019; Desai et
al. 2021; Edmonds et al. 2021; Indini et al. 2021)
Experienced ≥ Grade 3 immune related adverse events while on immunotherapy prior to
enrollment
Have not recovered from Grade 2 immune related adverse events attributed to
immunotherapy to Grade 1 or baseline prior to enrollment
NSCLC with epidermal growth factor receptor (EGFR) or anaplastic lymphoma receptor
tyrosine kinase (ALK) genomic tumor alterations
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 v. 5.0 ≥ Grade 3) or supplemental oxygen used to maintain
adequate oxygenation within 14 days prior to the planned first dose of investigational
product
Ongoing immune-related toxicity or immune-related toxicity requiring systemic
corticosteroids for 30 or more consecutive days for a prior immune related adverse
event before initiation of study treatment
•Prior drug-induced cardiotoxicity, defined as a sustained decrease in the ejection
fraction (EF) of > 15%
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