NCT04244552

Brief 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
87

participants targeted

Target at P75+ for phase_1 breast-cancer

Timeline
Completed

Started Feb 2020

Geographic Reach
1 country

19 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 21, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 28, 2020

Completed
14 days until next milestone

Study Start

First participant enrolled

February 11, 2020

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2023

Completed
Last Updated

December 29, 2023

Status Verified

December 1, 2023

Enrollment Period

3.7 years

First QC Date

January 21, 2020

Last Update Submit

December 26, 2023

Conditions

Outcome Measures

Primary Outcomes (1)

  • Incidence of DLTs (dose escalation cohorts only), treatment emergent adverse events (TEAEs), and changes in safety parameters

    24 months

Secondary Outcomes (9)

  • Maximum plasma concentration (Cmax) of ATRC-101

    24 months

  • Elimination half-life (t1/2) of ATRC-101

    24 months

  • Area under the plasma concentration-time curve from zero to the last measurable concentration [AUC(0-t)] of ATRC-101

    24 months

  • Incidence of anti-drug antibodies (ADAs) and ATRC-101 neutralizing antibodies

    24 months

  • Overall Response Rate (ORR), defined as the proportion of participants with a CR or a PR on two consecutive occasions > 4 weeks apart, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    24 months

  • +4 more secondary outcomes

Study Arms (4)

ATRC-101 Q3W

EXPERIMENTAL
Biological: ATRC-101

ATRC-101 Q2W

EXPERIMENTAL
Biological: ATRC-101

ATRC-101 Q3W + Pembrolizumab

EXPERIMENTAL

Pembrolizumab 200mg IV Q3W or 400mg IV Q6W

Biological: ATRC-101Biological: Pembrolizumab

ATRC-101 Q2W + Pegylated liposomal doxorubicin (PLD)

EXPERIMENTAL

PLD 40mg/m\^2 IV Run-in period of 28 days, and then 40mg/m\^2 IV Q4W

Biological: ATRC-101Drug: Pegylated liposomal doxorubicin (PLD)

Interventions

ATRC-101BIOLOGICAL

ATRC-101 is an engineered, fully-human IgG1 antibody derived from a naturally-occurring human antibody.

ATRC-101 Q2WATRC-101 Q2W + Pegylated liposomal doxorubicin (PLD)ATRC-101 Q3WATRC-101 Q3W + Pembrolizumab
PembrolizumabBIOLOGICAL

Pembrolizumab (Keytruda®) is a humanized immunoglobulin G4 monoclonal antibody with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2).

ATRC-101 Q3W + Pembrolizumab

Pegylated liposomal doxorubicin (PLD) is doxorubicin hydrochloride (HCl), an anthracycline topoisomerase inhibitor that can bind DNA and inhibit nucleic acid synthesis. PLD is doxorubicin HCL encapsulated in liposomes formulated with surface-bound methoxypolyethylene glycol

Also known as: DOXIL®, PLD
ATRC-101 Q2W + Pegylated liposomal doxorubicin (PLD)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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 months of the last dose of platinum-based chemotherapy OR breast cancer that 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.
  • 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 via central laboratory results:
  • Absolute neutrophil count (ANC)
  • For monotherapy and pembrolizumab combination therapy cohorts: ≥ 1000/µL
  • For PLD combination therapy cohort: ≥ 1500/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
  • +11 more criteria

You may not qualify if:

  • Individuals who meet any of the following criteria are not eligible to participate in this trial:
  • 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:
  • a. malignancies previously treated with curative intent with a 5-year OS rate \>90% (consultation with the Medical Monitor is required prior to enrollment).
  • 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 for the autoimmune disease.
  • Active or prior paraneoplastic neurologic disorder of the central nervous system (CNS) 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
  • For the PLD Combination Therapy Cohort:
  • Any history of documented congestive heart failure (CHF), arrhythmia, or uncontrolled hypertension (systolic BP \> 200 mmHg or diastolic BP \> 100 mmHg)
  • 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 2 weeks prior to the planned first dose of investigational product
  • +32 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California, Los Angeles Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Florida Cancer Specialists

Lake Mary, Florida, 32746, United States

Location

University of Miami Hospital - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Oncology Specialists of Charlotte

Charlotte, North Carolina, 28207, United States

Location

Carolina BioOncology

Huntersville, North Carolina, 28078, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Stephenson Cancer Center, University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Oncology Consultants, PLLC

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast NeoplasmsColorectal NeoplasmsOvarian NeoplasmsCarcinoma, Non-Small-Cell LungSquamous Cell Carcinoma of Head and NeckCarcinoma, HepatocellularEsophageal Squamous Cell CarcinomaCarcinoma, Transitional CellMelanomaTriple Negative Breast Neoplasms

Interventions

pembrolizumabliposomal doxorubicin1-dodecylpyridoxal

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesCarcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeHead and Neck NeoplasmsAdenocarcinomaLiver NeoplasmsLiver DiseasesNeoplasms, Squamous CellEsophageal NeoplasmsEsophageal DiseasesNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Nerve TissueNevi and MelanomasSkin Neoplasms

Study Officials

  • Sudha Khurana, PhD

    Atreca, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 21, 2020

First Posted

January 28, 2020

Study Start

February 11, 2020

Primary Completion

November 1, 2023

Study Completion

November 1, 2023

Last Updated

December 29, 2023

Record last verified: 2023-12

Data Sharing

IPD Sharing
Will not share

Locations