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A Phase 1b Trial of ATRC-101 in Adults With Advanced Solid Malignancies

Phase 1
Terminated
Conditions
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
Interventions
Biological: ATRC-101
Biological: Pembrolizumab
Registration Number
NCT04244552
Lead Sponsor
Atreca, Inc.
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.

Detailed 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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
87
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
ATRC-101 Q3WATRC-101-
ATRC-101 Q2WATRC-101-
ATRC-101 Q3W + PembrolizumabATRC-101Pembrolizumab 200mg IV Q3W or 400mg IV Q6W
ATRC-101 Q3W + PembrolizumabPembrolizumabPembrolizumab 200mg IV Q3W or 400mg IV Q6W
ATRC-101 Q2W + Pegylated liposomal doxorubicin (PLD)ATRC-101PLD 40mg/m\^2 IV Run-in period of 28 days, and then 40mg/m\^2 IV Q4W
ATRC-101 Q2W + Pegylated liposomal doxorubicin (PLD)Pegylated liposomal doxorubicin (PLD)PLD 40mg/m\^2 IV Run-in period of 28 days, and then 40mg/m\^2 IV Q4W
Primary Outcome Measures
NameTimeMethod
Incidence of DLTs (dose escalation cohorts only), treatment emergent adverse events (TEAEs), and changes in safety parameters24 months
Secondary Outcome Measures
NameTimeMethod
Maximum plasma concentration (Cmax) of ATRC-10124 months
Elimination half-life (t1/2) of ATRC-10124 months
Area under the plasma concentration-time curve from zero to the last measurable concentration [AUC(0-t)] of ATRC-10124 months
Incidence of anti-drug antibodies (ADAs) and ATRC-101 neutralizing antibodies24 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) v1.124 months
Levels of ATRC-101 immunoreactivity expressed as H-score, tumor proportion score, and maximum intensity24 months
For the PLD Combination Therapy Cohort: ATRC-101 immunoreactivity in tumor biopsies at baseline and during treatment24 months
Enumeration of tumor-infiltrating CD8+ lymphocytes (TILs) in tumor biopsy specimens at baseline and during treatment24 months
Distribution of tumor-infiltrating CD8+ lymphocytes (TILs) in tumor biopsy specimens at baseline and during treatment24 months

Trial Locations

Locations (17)

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

The University of Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

City of Hope

🇺🇸

Duarte, California, United States

University of California, Los Angeles Hematology/Oncology

🇺🇸

Los Angeles, California, United States

Georgetown University Medical Center

🇺🇸

Washington, District of Columbia, United States

Florida Cancer Specialists

🇺🇸

Lake Mary, Florida, United States

University of Miami Hospital - Sylvester Comprehensive Cancer Center

🇺🇸

Miami, Florida, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Nebraska Cancer Specialists

🇺🇸

Omaha, Nebraska, United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

🇺🇸

New York, New York, United States

Scroll for more (7 remaining)
Mayo Clinic
🇺🇸Rochester, Minnesota, United States

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