Breast CancerPhase 1NCT04244552
A Phase 1b Trial of ATRC-101 in Adults With Advanced Solid Malignancies
A Phase 1 study testing ATRC-101, Pembrolizumab and Pegylated liposomal doxorubicin (PLD) in people with Breast Cancer and Colorectal Cancer, run by Atreca, Inc. at 19 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Colorectal Cancer, Ovarian Cancer
- What is being tested?
- ATRC-101, Pembrolizumab and Pegylated liposomal doxorubicin (PLD)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 19 sitesUnited States
- Study dates
- 11 Feb 2020to 1 Nov 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- 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
- 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 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.
- 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.
- 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
- Willing and able to provide written informed consent and able to comply with all trial procedures
Who cannot join
- 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:
- 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
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- Prior allogenic hematopoietic or solid organ transplant, including allogeneic cellular therapy (e.g., allogeneic chimeric antigen receptor (CAR)-modified T cells). Allogeneic bone grafts are not exclusionary.
- 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
- Ongoing ≥ Grade 2 toxicity(ies) due to a previously administered anticancer agent with the following exceptions:
- Grade 2 neuropathy or alopecia
- 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
- For the PLD combination therapy cohort:
- Prior treatment with PLD
- Prior treatment with doxorubicin or other anthracycline at cumulative doses greater than 300mg/m2.
- 1. 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
- Prior mediastinal irradiation > 3500 cGY
- 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
- 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. 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)
- For the pembrolizumab combination therapy cohort ONLY:
- 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
- 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 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
- For the PLD combination therapy cohort ONLY:
- •Prior drug-induced cardiotoxicity, defined as a sustained decrease in the ejection fraction (EF) of > 15%.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Gabrail Cancer Center
Canton, Ohio, 44718
Oncology Specialists of Charlotte
Charlotte, North Carolina, 28207
City of Hope
Duarte, California, 91010
Oncology Consultants, PLLC
Houston, Texas, 77030
Carolina BioOncology
Huntersville, North Carolina, 28078
Mayo Clinic
Jacksonville, Florida, 32224
Florida Cancer Specialists
Lake Mary, Florida, 32746
University of California, Los Angeles Hematology/Oncology
Los Angeles, California, 90095
University of Miami Hospital - Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Stephenson Cancer Center, University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Nebraska Cancer Specialists
Omaha, Nebraska, 68130
Mayo Clinic
Phoenix, Arizona, 85054
Mayo Clinic
Rochester, Minnesota, 55902
The University of Arizona Cancer Center
Tucson, Arizona, 85719
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Breast Cancer, Colorectal Cancer, Ovarian Cancer, Non-Small Cell Lung Cancer, Acral Lentiginous Melanoma, Head and Neck Squamous Cell Carcinoma
- Being tested
- ATRC-101, Pembrolizumab, Pegylated liposomal doxorubicin (PLD)
- Medical subject headings
- Breast Neoplasms, Colorectal Neoplasms, Ovarian Neoplasms, Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Hepatocellular, Esophageal Squamous Cell Carcinoma, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATRC-101Biological
ATRC-101 is an engineered, fully-human IgG1 antibody derived from a naturally-occurring human antibody.
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).
Pegylated liposomal doxorubicin (PLD)Drug
Also called DOXIL®, PLD
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
| Study group | Role | What they receive |
|---|---|---|
| ATRC-101 Q3W | Experimental | Not described Receives: Biological: ATRC-101 |
| ATRC-101 Q2W | Experimental | Not described Receives: Biological: ATRC-101 |
| ATRC-101 Q3W + Pembrolizumab | Experimental | Pembrolizumab 200mg IV Q3W or 400mg IV Q6W Receives: Biological: ATRC-101; Biological: 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 Receives: Biological: ATRC-101; Drug: Pegylated liposomal doxorubicin (PLD) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of DLTs (dose escalation cohorts only), treatment emergent adverse events (TEAEs), and changes in safety parameters
Measured: 24 months
Secondary outcomes (9)
Maximum plasma concentration (Cmax) of ATRC-101
Measured: 24 months
Elimination half-life (t1/2) of ATRC-101
Measured: 24 months
Area under the plasma concentration-time curve from zero to the last measurable concentration [AUC(0-t)] of ATRC-101
Measured: 24 months
Incidence of anti-drug antibodies (ADAs) and ATRC-101 neutralizing antibodies
Measured: 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
Measured: 24 months
Enumeration of tumor-infiltrating CD8+ lymphocytes (TILs) in tumor biopsy specimens at baseline and during treatment
Measured: 24 months
Distribution of tumor-infiltrating CD8+ lymphocytes (TILs) in tumor biopsy specimens at baseline and during treatment
Measured: 24 months
Levels of ATRC-101 immunoreactivity expressed as H-score, tumor proportion score, and maximum intensity
Measured: 24 months
For the PLD Combination Therapy Cohort: ATRC-101 immunoreactivity in tumor biopsies at baseline and during treatment
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2020
- Study start11 Feb 2020
- Primary completion1 Nov 2023
- Study completion1 Nov 2023
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Atreca, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sudha Khurana, PhD, Study director, Atreca, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04244552
- Sponsor's protocol ID
- ATRC-101-A01
- Status last verified
- Dec 2023
- First submitted
- 21 Jan 2020
- Last updated
- 29 Dec 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04244552
- Acronym / sponsor ID
- ATRC-101-A01
- Conditions
- Breast Cancer, Colorectal Cancer, Ovarian Cancer, Non-Small Cell Lung Cancer, Acral Lentiginous Melanoma, Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Atreca, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Feb 2020 (actual)
- Primary completion
- 1 Nov 2023 (actual)
- Study completion
- 1 Nov 2023 (actual)
- First posted
- 28 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ATRC-101 Q3W | Experimental | Biological: ATRC-101 |
| ATRC-101 Q2W | Experimental | Biological: ATRC-101 |
| ATRC-101 Q3W + Pembrolizumab | Experimental | Biological: ATRC-101, Biological: PembrolizumabPembrolizumab 200mg IV Q3W or 400mg IV Q6W |
| ATRC-101 Q2W + Pegylated liposomal doxorubicin (PLD) | Experimental | Biological: ATRC-101, Drug: Pegylated liposomal doxorubicin (PLD)PLD 40mg/m^2 IV Run-in period of 28 days, and then 40mg/m^2 IV Q4W |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- 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.
- 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.
Key exclusion criteria (49 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ATRC-101ATRC-101 is an engineered, fully-human IgG1 antibody derived from a naturally-occurring human antibody. | Biological | ATRC-101 Q2W, ATRC-101 Q2W + Pegylated liposomal doxorubicin (PLD), ATRC-101 Q3W, ATRC-101 Q3W + Pembrolizumab |
| PembrolizumabPembrolizumab (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). | Biological | ATRC-101 Q3W + Pembrolizumab |
| Pegylated liposomal doxorubicin (PLD)Also: DOXIL®, PLDPegylated 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 | Drug | ATRC-101 Q2W + Pegylated liposomal doxorubicin (PLD) |
Primary outcome
Incidence of DLTs (dose escalation cohorts only), treatment emergent adverse events (TEAEs), and changes in safety parameters
Time frame: 24 months
9 secondary outcomes
Maximum plasma concentration (Cmax) of ATRC-101
Time frame: 24 months
Elimination half-life (t1/2) of ATRC-101
Time frame: 24 months
Area under the plasma concentration-time curve from zero to the last measurable concentration [AUC(0-t)] of ATRC-101
Time frame: 24 months
Incidence of anti-drug antibodies (ADAs) and ATRC-101 neutralizing antibodies
Time frame: 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
Time frame: 24 months
Enumeration of tumor-infiltrating CD8+ lymphocytes (TILs) in tumor biopsy specimens at baseline and during treatment
Time frame: 24 months
Distribution of tumor-infiltrating CD8+ lymphocytes (TILs) in tumor biopsy specimens at baseline and during treatment
Time frame: 24 months
Levels of ATRC-101 immunoreactivity expressed as H-score, tumor proportion score, and maximum intensity
Time frame: 24 months
For the PLD Combination Therapy Cohort: ATRC-101 immunoreactivity in tumor biopsies at baseline and during treatment
Time frame: 24 months
Results and safety
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2023.
- Individual participant dataSharing planned: No
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Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sudha Khurana, PhD study director
Atreca, Inc.
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ATRC-101, Pembrolizumab and Pegylated liposomal doxorubicin (PLD) in people with Breast Cancer and Colorectal Cancer, run by Atreca, Inc. at 19 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 49 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of DLTs (dose escalation cohorts only), treatment emergent adverse events (TEAEs), and changes in safety parameters (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2023.