AzTrials
AzTrials

Metastatic Soft Tissue SarcomaPhase 2NCT04028063

Doxorubicin Plus Dual Checkpoint Blockade for Soft Tissue Sarcomas

A Phase 2 study testing Balstilimab, Zalifrelimab and Doxorubicin in people with Metastatic Soft Tissue Sarcoma and Advanced Soft Tissue Sarcoma, run by University of Colorado, Denver at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is an open-label, non-randomized, single-institution, single arm Phase II study conducted using a Simon two-stage design with an additional safety lead-in. The overall objective is to determine the efficacy of combination doxorubicin with dual checkpoint blockade with anti-CTLA-4 antibody AGEN1884 and anti-PD-1… Read more about this study

Who is it for?
Ages 18 to 100 years
What is being tested?
Balstilimab, Zalifrelimab and Doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
1 siteUnited States
Study dates
28 Jan 2020to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Part One:
  • Provision to sign and date the consent form.
  • Stated willingness to comply with all study procedures and be available for the duration of the study.
  • Be male or female aged 18-100 years at the time of signing informed consent.
  • Have a histological diagnosis of advanced or metastatic soft tissue sarcoma (STS) (by local pathology review), not curable by surgery, for which treatment with doxorubicin is deemed appropriate by the investigator.
  • Has one of the following histologies:
Show all 77Show fewer
  • synovial sarcoma,
  • malignant peripheral nerve sheath tumors,
  • dedifferentiated, pleomorphic or myxoid/round cell liposarcoma,
  • uterine or soft tissue leiomyosarcoma,
  • malignant phylloides tumor,
  • high grade undifferentiated pleomorphic sarcomas (HGUPS/MFH),
  • myxofibrosarcoma,
  • fibrosarcoma,
  • angiosarcoma,
  • spindle cell or undifferentiated sarcoma NOS,
  • malignant myoepithelioma,
  • malignant solitary fibrous tumor/hemangiopericytoma,
  • epithelioid hemangioendothelioma,
  • Any other histology or standard of care treatment not specifically addressed will be reviewed by the principal investigator and pathologist for final determination of eligibility.
  • Have measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Tumors within a previously irradiated field will be designated as "nontarget" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy.
  • Have received 0 or 1 prior systemic therapies for metastatic sarcoma and NO prior anthracyclines or checkpoint inhibitors.
  • Adequate organ function as defined in protocol.
  • Absolute neutrophil count (ANC) ≥1,000 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥8 g/dL without EPO dependency
  • Serum creatinine OR Measured or calculated creatiniecclearance
  • ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
  • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN Exception: Subjects with known history of Gilbert's disease should be ≤ 1.5 X of the patient's prior baseline AST (SGOT) and ALT (SGPT) ≤2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Albumin >2.5 mg/dL
  • International Normalized Ratio (INR) or Prothrombin Time (PT)
  • ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Creatinine clearance should be calculated per institutional standard.
  • ECOG performance status of 0 or 1.
  • Patients must consent and be willing to undergo tumor core needle biopsies at two timepoints: 1. Baseline, 2. Cycle 2 Day 5; a third biopsy for off-study/progression is optional but advised. At least one tumor site must be amenable to biopsy in the judgment of the interventional radiologist.
  • Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Females of child bearing potential that are sexually active must agree to either practice 2 medically accepted highly effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 120 days after the last dose of study drug. See Appendix B for protocol-approved highly effective methods of contraceptive combinations. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Negative test for pregnancy is required of females of child-bearing potential. A female of child-bearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1. Has not undergone a hysterectomy or bilateral oophorectomy; or 2. Has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months or 730 days.)
  • Conception while on treatment must be avoided.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Prior history of vasectomy does NOT replace requirement for contraceptive use.
  • Subjects must either possess or undergo placement of central venous catheter, including pheresis or trifusion catheter, PICC line, or port.
  • Part Two: In order to be eligible to participate in this study, an individual must meet all of the following criteria:
  • Provision to sign and date the consent form.
  • Stated willingness to comply with all study procedures and be available for the duration of the study.
  • Be male or female aged 18-100 years at the time of signing informed consent.
  • Have a histological diagnosis of advanced or metastatic soft tissue sarcoma (STS) (by local pathology review), not curable by surgery, for which treatment with doxorubicin is deemed appropriate by the investigator.
  • Has one of the following histologies:
  • synovial sarcoma,
  • malignant peripheral nerve sheath tumors,
  • dedifferentiated, pleomorphic or myxoid/round cell liposarcoma,
  • uterine or soft tissue leiomyosarcoma,
  • malignant phylloides tumor,
  • high grade undifferentiated pleomorphic sarcomas (HGUPS/MFH),
  • myxofibrosarcoma,
  • fibrosarcoma,
  • angiosarcoma,
  • spindle cell or undifferentiated sarcoma NOS,
  • malignant myoepithelioma,
  • malignant solitary fibrous tumor/hemangiopericytoma,
  • epithelioid hemangioendothelioma,
  • Any other histology or standard of care treatment not specifically addressed will be reviewed by the principal investigator in consultation with pathology as needed for final determination of eligibility.
  • Have measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (modified RECIST 1.1). Tumors within a previously irradiated field will be designated as "nontarget" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy.
  • Have received any number of prior systemic therapies for metastatic sarcoma but NO prior anthracyclines or checkpoint inhibitors. Re-treatment with the same drug or regimen after interruption (i.e. chemotherapy holiday) is not considered a new line of treatment, and those patients are eligible.
  • Adequate organ function as defined in protocol.
  • Absolute neutrophil count (ANC) ≥1,000 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥8 g/dL without EPO dependency
  • Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)
  • ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
  • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN. Exception: Subjects with known history of Gilbert's disease should be ≤ 1.5 X of the patient's prior baseline
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Albumin >2.5 mg/dL
  • International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Creatinine clearance should be calculated per institutional standard.
  • ECOG performance status of 0 or 1.
  • Patients must consent and be willing to undergo tumor core needle biopsies at two timepoints: 1. Baseline, 2. Cycle 2 Day 5; a third biopsy for off-study/progression is optional but advised. At least one tumor site must be amenable to biopsy in the judgment of the investigator, with consultation with the interventional radiologist as needed.
  • Female subjects of childbearing potential must have a negative urine or serum pregnancy test at screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the rare case where the sarcoma is thought to be producing beta HCG, patients with a positive serum HCG test must have a uterine ultrasound for confirmation of negative pregnancy status.
  • Females of child bearing potential that are sexually active must agree to either practice 2 medically accepted highly effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 120 days after the last dose of study drug. See Appendix B for protocol-approved highly effective methods of contraceptive combinations. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Negative test for pregnancy is required of females of child-bearing potential. A female of child-bearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1. Has not undergone a hysterectomy or bilateral oophorectomy; or 2. Has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months or 730 days.)
  • Conception while on treatment must be avoided.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Prior history of vasectomy does NOT replace requirement for contraceptive use.
  • Subjects must either possess or undergo placement of central venous catheter, including pheresis or trifusion catheter, PICC line, or port.

Who cannot join

  • Part One:
  • Prior therapy with anthracycline or checkpoint inhibitors.
  • Hypersensitivity to doxorubicin or any excipients.
  • Patients may not be receiving any other investigational agents (within 4 weeks prior to Cycle 1, Day 1).
  • Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to Cycle 1, Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Patient has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Cycle 1, Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Subjects with ≤ Grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
Show all 40Show fewer
  • Additional known malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
  • Patients with underlying immune deficiency, chronic infections including HIV, hepatitis, or tuberculosis (TB) or autoimmune disease.
  • Patients with underlying hematologic issues including bleeding diathesis, such as known previous GI bleeding requiring intervention within the past 6 months. Newly diagnosed pulmonary emboli or deep venous thrombosis must be clinically stable on anticoagulation regimen for ≥ 2 weeks as of Cycle 1 Day 1.
  • Has known history of non-infectious pneumonitis that required oral corticosteroid therapy for resolution within 12 months prior to study entry, or evidence by imaging or symptoms of active non-infectious pneumonitis.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease. Subjects with previously treated brain metastases may participate provided they are stable based on the following: 1) MRI brain obtained during screening evaluations shows no radiographic evidence of progression or new lesions, 2) any neurologic symptoms have returned to baseline, 3) no requirement for steroids for at least 28 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Patients without a known history of brain metastases do not require screening brain MRI prior to study enrollment.
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Any uncontrolled, intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
  • Prolonged QTc interval on Screening EKG >475 ms.
  • Ejection Fraction <50% by 2D ECHO at Screening.
  • Any serious medical or psychiatric illness/condition including substance use disorders likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment, including NYHA Class II or greater heart disease (see Appendix C for definitions).
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Had a previous severe hypersensitivity reaction to another monoclonal antibody.
  • Primary or secondary immunodeficiency (including immunosuppressive disease, autoimmune disease [excluding hypothyroidism, insulin dependent diabetes mellitus, or vitiligo], or usage of immunosuppressive medications).
  • Part Two: An individual who meets any of the following criteria will be excluded from participation in this study:
  • Prior therapy with anthracycline or checkpoint inhibitors.
  • Hypersensitivity to doxorubicin or any excipients.
  • Patients may not be receiving any other investigational agents (within 4 weeks prior to Cycle 1, Day 1).
  • Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to Cycle 1, Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Patient has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Cycle 1, Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. Subjects with ≤ Grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Additional known malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
  • Patients with underlying immune deficiency, chronic infections including HIV, hepatitis, or tuberculosis (TB) or autoimmune disease.
  • Patients with underlying hematologic issues including bleeding diathesis, such as known previous GI bleeding requiring intervention within the past 6 months. Newly diagnosed pulmonary emboli or deep venous thrombosis must be clinically stable on anticoagulation regimen for ≥ 2 weeks as of Cycle 1 Day 1.
  • Has known history of non-infectious pneumonitis that required oral corticosteroid therapy for resolution within 12 months prior to study entry, or evidence by imaging or symptoms of active non-infectious pneumonitis.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease. Subjects with previously treated brain metastases may participate provided they are stable based on the following: 1) MRI brain obtained during screening evaluations shows no radiographic evidence of progression or new lesions, 2) any neurologic symptoms have returned to baseline, 3) no requirement for steroids for at least 28 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Patients without a known history of brain metastases do not require screening brain MRI prior to study enrollment.
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Any uncontrolled, intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
  • Prolonged QTc interval on Screening EKG >475 ms.
  • Ejection Fraction <50% by 2D ECHO at Screening.
  • Any serious medical or psychiatric illness/condition including substance use disorders likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment, including NYHA Class II or greater heart disease (see Appendix C for definitions).
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Had a previous severe hypersensitivity reaction to another monoclonal antibody.
  • Primary or secondary immunodeficiency (including immunosuppressive disease, autoimmune disease [excluding hypothyroidism, insulin dependent diabetes mellitus, or vitiligo], or usage of immunosuppressive medications).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Colorado Hospital

    Aurora, Colorado, 80045

Other trials in United States

About this study

Official title: An Open-Label, Phase II Efficacy Trial of Doxorubicin in Combination With Dual Checkpoint Blockade Using Zalifrelimab (AGEN1884) or Botensilimab (AGEN1181) With Balstilimab (AGEN2034) for Advanced or Metastatic Soft Tissue Sarcomas

This is an open-label, non-randomized, single-institution, single arm Phase II study conducted using a Simon two-stage design with an additional safety lead-in. The overall objective is to determine the efficacy of combination doxorubicin with dual checkpoint blockade with anti-CTLA-4 antibody AGEN1884 and anti-PD-1 antibody AGEN2034. The investigators will estimate the progression-free survival rate at 6 months (PFS6mo) of doxorubicin plus AGEN1884/AGEN2034 in comparison to historical PFS6mo with doxorubicin monotherapy, calculated as the mean from two large randomized Phase 3 clinical trials.

Read the detailed description

The primary endpoint for the study is PFS6mo by RECIST 1.1. The sample size calculation is based on a Simon Two-Stage design with incorporation of early stopping rules for safety and futility (See section 9 for statistical considerations). The Investigators will enroll up to 35 patients on the study to obtain 28 evaluable patients for the primary endpoint. Safety of the combination will be evaluated after the first six patients complete the DLT observation period of 9 weeks. This lengthy DLT period is designed to capture safety and toxicity profile, understanding that immune-related toxicities from checkpoint inhibitors may not emerge immediately. This will also ensure adequate evaluation of potential cardiac and hepatic toxicity from combination doxorubicin and checkpoint inhibitor therapy. If two or more patients experience DLT in the initial safety lead-in cohort, the regimen will be declared intolerable. Any patients who do not complete study therapy through the 9-week DLT observation period for any reasons other than toxicity will be replaced for safety lead-in assessment. If fewer than two patients experience DLT, the investigators will proceed to expansion to complete enrollment of 15 patients in Stage 1. Following enrollment of stage one, accrual will pause for analysis of efficacy. If 6 or fewer of the 15 patients are progression-free at 6 months, the investigators will halt the study for futility. If 7 or more patients are free from progression, then the investigators will proceed with enrollment of 13 additional patients to complete stage 2. the investigators are powered to detect improvement in 6-month PFS rate to 63.4% with the combination over the 43.4% historical PFS6mo.

Being tested
Balstilimab, Zalifrelimab, Doxorubicin, Botensilimab
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BalstilimabDrug

    Also called AGEN2034

    Balstilimab (AGEN2034) is a human monoclonal antibody that targets programmed cell death 1 (PD-1). Engagement of PD-1 by its ligands, programmed death ligand (PD-L1) and PD-L2, leads to signal transduction that inhibits important aspects of T cell function including proliferation, cytokine production and cytolytic activity. Balstilimab (AGEN2034) potently inhibits PD-1 binding to PD- L1 and PD- L2 and is intended to reverse the immunosuppressive effects of this signaling pathway in the context of tumor immuno-surveillance by T cells. Balstilimab (AGEN2034) is intended for development as a treatment for advanced malignancies as a single agent or in combinations.

  • ZalifrelimabDrug

    Also called AGEN1884

    Zalifrelimab (AGEN1884) is a fully human monoclonal immunoglobulin G1 κ subclass (IgG1κ) antibody that specifically recognizes cytotoxic T lymphocyte-associated protein 4 (CTLA-4, also known as CD152). Zalifrelimab (AGEN1884) is being developed as a monotherapy for cancer indications with potential for future development in combination with other immunotherapies.

  • DoxorubicinDrug

    Also called Lipodox, Doxil

    Doxorubicin is the standard of care first-line therapy for most subtypes of metastatic soft tissue sarcomas. Doxorubicin monotherapy administered at 75 mg/m2 has resulted in objective response rate of 14%, and median progression-free survival of 4.6 months, and another study reported progression-free survival at 6 months of 46.3%, with a median PFS of 5.8 months, and best objective response rate of 19%.

  • BotensilimabDrug

    Also called AGEN1181

    Botensilimab (AGEN1181) is a novel, human, fragment-crystallizable (Fc)-engineered immunoglobulin G1 (IgG1) anti-CTLA-4 antibody designed to exploit a novel mechanism by which increased Fc engagement enhances antigen-specific effector T cell responses.

Study groups in NCT04028063
Study groupRoleWhat they receive
Part 1: Stage 1, Safety Lead-InExperimentalThe safety lead-in will enroll 6 participants. Balstilimab 300mg flat q3 weeks up to 2 years; Zalifrelimab 1mg/kg q6 weeks x 4; Doxorubicin 75mg/m2 q3 weeks x 2, starts at C2 The participants will complete a dose-limiting toxiciy (DLT) observation period of 9 weeks.
Receives: Drug: Balstilimab; Drug: Zalifrelimab; Drug: Doxorubicin
Part 1: Stage 2, ExpansionExperimentalBalstilimab 300mg flat q3 weeks up to 2 years; Zalifrelimab 1mg/kg q6 weeks up to 2 years; Doxorubicin 75mg/m2 q3 weeks x 6
Receives: Drug: Balstilimab; Drug: Zalifrelimab; Drug: Doxorubicin
Part 2: Stage 2, Dose 1ExperimentalDoxorubicin 60mg/m2 q3 weeks x 6 doses Botensilimab 75mg q6 weeks up to two years
Receives: Drug: Doxorubicin; Drug: Botensilimab
Stage 2, Dose 2ExperimentalDoxorubicin 75mg/m2 q3 weeks x 6 doses Botensilimab 75mg q6 weeks up to two years
Receives: Drug: Doxorubicin; Drug: Botensilimab
Stage 2, Dose 3 Combination of Doxorubicin with Botensilimab and BalstilimabExperimentalDoxorubicin 75mg/m2 q3 weeks x 6 doses Botensilimab 75mg flat q6 weeks up to 2 years Balstilimab 450mg q3 weeks up to 2 years
Receives: Drug: Balstilimab; Drug: Doxorubicin; Drug: Botensilimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determine the progression-free survival rate

    Determine the progression-free survival rate at 6 months of combination therapy with doxorubicin, AGEN1884, and AGEN2034 in anthracycline-naïve patients with advanced or metastatic soft tissue sarcomas.

    Measured: 6 months

Secondary outcomes (4)

  1. Determine the overall response rate

    Determine the overall response rate of combination therapy with doxorubicin, AGEN1884, and AGEN2034 in anthracycline-naïve patients with advanced or metastatic soft tissue sarcomas.

    Measured: 3 years

  2. Determine the clinical benefit rate

    Determine the clinical benefit rate of combination therapy with doxorubicin, AGEN1884, and AGEN2034 in anthracycline-naïve patients with advanced or metastatic soft tissue sarcomas.

    Measured: 3 years

  3. Determine the duration of response

    Determine the duration of response of combination therapy with doxorubicin, AGEN1884, and AGEN2034 in anthracycline-naïve patients with advanced or metastatic soft tissue sarcomas.

    Measured: 3 years

  4. Determine the incidence of adverse events

    Determine adverse events occurring with combination therapy of doxorubicin, AGEN1884, and AGEN2034 in anthracycline-naïve patients with advanced or metastatic soft tissue sarcomas.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2019
  2. Study start28 Jan 2020
  3. Primary completion7 Apr 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
This is an open-label, non-randomized, single-institution, single arm Phase II study conducted using a Simon two-stage design with an additional safety lead-in.
Masking
None (open label)
Enrolment
65 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04028063
Sponsor's protocol ID
19-0554.cc
Other IDs
NCI-2020-00728
Status last verified
Jan 2026
First submitted
17 Jul 2019
Last updated
20 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Balstilimab, Zalifrelimab and Doxorubicin in people with Metastatic Soft Tissue Sarcoma and Advanced Soft Tissue Sarcoma, run by University of Colorado, Denver at 1 site 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 77 inclusion and 40 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: under way, not looking for participants, as of the sponsor's last update on 20 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Determine the progression-free survival rate (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04028063.

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 20 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in