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Anatomic Stage IV Breast Cancer AJCC v8Phase 1NCT04616248

In Situ Immunomodulation With CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients w/ Unresectable and Metastatic Solid Tumors

A Phase 1 study testing Anti-CD40 Agonist Monoclonal Antibody CDX-1140, Poly ICLC and Radiation Therapy in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Breast Carcinoma, run by University of Southern California at 2 sites 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 phase I trial evaluates the safety and effectiveness of in situ immunomodulation with CDX-301, radiotherapy, CDX-1140 and Poly-ICLC (Cohort A) and these with intravenous (IV) pembrolizumab and subcutaneous (SC) tocilizumab (Cohort B) in treating patients with unresectable and measurable metastatic melanoma… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anti-CD40 Agonist Monoclonal Antibody CDX-1140, Poly ICLC and Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
2 sitesUnited States
Study dates
9 Jan 2023to 9 Jan 2028
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have clinically or pathologically confirmed diagnosis of unresectable and metastatic melanoma, cutaneous SCC, basal cell carcinoma, Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or HER2/neu (-) breast cancer with no curative treatment options.
  • The unresectable disease to be irradiated and injected with medications must be located in breast, dermal, subcutaneous, or soft tissue, or lymph nodes with the longest axis of the tumor 2-7 centimeters, and should be considered safe for injection by the investigator.
  • The metastatic disease must be measured per irRECIST criteria.
  • Patient must have lesion that can be biopsied and is willing to undergo the procedure as part of the protocol.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 1.
  • Participants of child-bearing potential and men must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
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  • For patients with history of radiotherapy to the same location that will be treated on study, he/she will be eligible only if the prior radiation dose was under or equal to 68 Gy total and delivered more than 6 months prior to planned re-treatment. (The cumulative dose received to the irradiated area will be no more than 87 Gy total, including a maximum of 68 Gy allowed from prior treatment course.)
  • Patient requires the use of radiation therapy to the target lesion of palliation of symptoms and/or achieving local control as part of standard of care as deemed appropriate by treating radiation oncologist.
  • Patients must agree to radiation to the tumor.
  • Any line of therapy allowed, radiologically or clinically confirmed progression on prior therapy
  • Must have adequate organ and marrow function present as defined below:
  • Platelets >= 100,000/uL
  • Hemoglobin >= 8.0 g/dL
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN.
  • Creatinine =< 1.5 X ULN OR creatinine clearance >= 50 mL/min per Cockcroft-Gault equation for patients with creatinine levels greater than ULN.
  • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
  • Patients must agree to injections of CDX-301, CDX-1140, and poly-ICLC.
  • Patients must agree to appropriate clinical monitoring to receive the study regimens.
  • Patients must agree to photos of tumors and use of the photos for publication.
  • Patients should have an administration site for all injections that is free of potentially complicating dermatologic conditions such as rashes.

Who cannot join

  • Patients currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment. (inhaled steroids are allowed)
  • Patients with HER2+ breast cancer
  • Concurrent use of targeted therapy including CDK4/6, mTOR, PIK3CA, PARP, BRAF, MEK, hedgehog inhibitors or chemotherapy (endocrine therapy is allowed).
  • Targeted therapy including CDK4/6, mTOR, PIK3CA, PARP, BRAF, MEK, hedgehog inhibitors, chemotherapy, or immunotherapy within 2 weeks prior to first dosing of study agent. (endocrine therapy is allowed).
  • Patients with active or history of autoimmune disease or history of transplantation except for the patients with Graves' disease with ablative therapy of total thyroidectomy.
  • Patients with history of (non-infectious) pneumonitis/interstitial lung disease, including grade 1 pneumonitis (asymptomatic; clinical or diagnostic observations only; intervention not indicated).
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  • Patients with prior history of acute myeloid leukemia (AML) or known FLT3 aberrations
  • Pregnant or nursing female participants.
  • Unwilling or unable to follow protocol requirements.
  • Patients with known serious mood disorders. (Major depression diagnosis is an exclusion: Other stable mood disorders on stable therapy for > 6 months or not requiring therapy may be allowed after consultation with principal investigator [PI]).
  • Cardiac risk factors including:
  • Patients experiencing cardiac event(s) (acute coronary syndrome, myocardial infarction, or ischemia) within 3 months of signing consent.
  • Patients with a New York Heart Association classification of III or IV.
  • Patients with uveal melanoma.
  • Patients with uncontrolled diseases other than cancer may be excluded if after consultation with PI and research team it is decided it might affect the treatment efficacy or toxicity.
  • Evidence of current drug or alcohol abuse or psychiatric impairment, which in the investigator's opinion will prevent completion of the protocol therapy or follow-up. Specific testing is not required, however may be done as clinically indicated.
  • Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug.
  • Participants with symptomatic known brain metastases < 4 weeks from radiation treatment should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Other invasive cancers diagnosed < 3 years back that required systemic treatment. If diagnosed with other invasive cancer >= 3 years, should have complete recovery from all systemic toxicity except neuropathy, vitiligo, alopecia, and endocrinopathies on stable hormone replacement therapy.
  • Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine.
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected).
  • Current use of anticoagulants (warfarin, heparin) at therapeutic levels.
  • Patients who have had stroke/TIA and DVT/PE within the last 12 months.
  • Patients at risk for impending visceral crisis of the liver and lungs as follows, or any condition which in the patient's primary treating oncologist's opinion deems the participant an unsuitable candidate to receive study drug:
  • A visceral crisis of the liver exists when bilirubin levels increase very rapidly (>1.5 times the upper limit of normal) without the presence of Gilbert syndrome (i.e., Meulengracht syndrome) or a biliary tract obstruction.
  • A visceral crisis of the lungs can be assumed when dyspnea at rest increases more rapidly and cannot be relieved by pleural drainage.
  • Radiation induced angiosarcoma.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

Other trials in United States

About this study

Official title: A Phase I Study of In Situ Immunomodulation With CDX-301, Radiotherapy, CDX-1140, and Poly-ICLC in Patients With Unresectable and Metastatic Solid Tumors With Injectable Palpable Disease

This phase I trial evaluates the safety and effectiveness of in situ immunomodulation with CDX-301, radiotherapy, CDX-1140 and Poly-ICLC (Cohort A) and these with intravenous (IV) pembrolizumab and subcutaneous (SC) tocilizumab (Cohort B) in treating patients with unresectable and measurable metastatic melanoma, cutaneous squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or HER2/neu(-) breast cancer. CDX-301 may induce cross-presenting dendritic cells, master regulators in the immune system. Radiation therapy uses high energy to kill tumor cells and release antigens that may be picked up, processed and presented by cross-presenting dendritic cells. CDX-1140 and Poly-ICLC may activate tumor antigen-loaded,cross-presenting dendritic cells, and generate tumor-specific T lymphocytes, a type of immune cells, that can search out and attack cancers. Giving immune modulators and radiation therapy may stimulate tumor cell death and activate the immune system.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety profile of in situ immunomodulation with CDX-301, radiotherapy, CDX-1140, and Poly-ICLC (Cohort A) and these with pembrolizumab (IV) and tocilizumab (SC) (Cohort B) in unresectable and metastatic melanoma, cutaneous squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or breast cancer patients with injectable palpable disease by determining the maximum tolerated dose (MTD) of CDX-1140 that has an acceptable adverse event profile.

SECONDARY OBJECTIVE:

  1. To evaluate the immune signatures in the tumor microenvironment before and after in situ immunomodulation with CDX-301, radiotherapy, CDX-1140, and Poly-ICLC (Cohort A) and these with pembrolizumab (IV) and tocilizumab (SC) (Cohort B).

EXPLORATORY OBJECTIVES:

  1. To record the overall response rate (ORR) (complete response [CR] and partial response [PR]) of injected as well as distant uninjected metastatic lesions in metastatic melanoma, cutaneous SCC, basal cell carcinoma, Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or breast cancer patients with injectable palpable disease treated with in situ immunomodulation with CDX-301, radiotherapy, CDX-1140, and Poly-ICLC (Cohort A) and these with pembrolizumab (IV) and tocilizumab (SC) (Cohort B) by immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) response assessment.

II. To record the overall survival (OS) and progression free survival (PFS) in unresectable and metastatic melanoma, cutaneous SCC, basal cell carcinoma, Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or breast cancer patients with injectable palpable disease treated with in situ immunomodulation with CDX-301, radiotherapy, CDX-1140, and Poly-ICLC (Cohort A) and these with pembrolizumab (IV) and tocilizumab (SC) (Cohort B).

III. Examine changes in the levels of T-cell subsets/myeloid derived suppressor cells (MDSC)/cytokines in peripheral blood (PB) of unresectable and metastatic melanoma, cutaneous SCC, basal cell carcinoma, Merkel cell carcinoma, high-grade bone and soft tissue sarcoma or breast cancer patients with injectable palpable disease treated with in situ immunomodulation with CDX-301, radiotherapy, CDX-1140, and Poly-ICLC (Cohort A) and these with pembrolizumab (IV) and tocilizumab (SC) (Cohort B).

OUTLINE:Cohort A will evaluate safety of intratumoral administration of CDX-1140 in combination with CDX-301, radiotherapy and Poly-ICLC. Once cohort A is finished, patients will be enrolled to cohort B to evaluate safety of intratumoral + intravenous administration of CDX-1140 in combination with CDX-301, radiotherapy, pembrolizumab, tocilizumab, and Poly-ICLC.

COHORT A: Patients receive recombinant Flt3 ligand intratumorally (IT) on days 1-5 and agonistic anti-CD40 monoclonal antibody CDX-1140 IT with Poly-ICLC IT on day 9 or 10. Patients also undergo radiation therapy on day 8 or 9. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

COHORT B: Patients receive recombinant Flt3 ligand IT on days 1-5 and agonistic anti-CD40 monoclonal antibody CDX-1140 IT and intravenously (IV) over 90 minutes with Poly-ICLC IT on day 9 or 10. Patients also receive pembrolizumab (IV), tocilizumab (SC), as well as undergo radiation therapy on day 8 or 9. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for 2 years.

Being tested
Anti-CD40 Agonist Monoclonal Antibody CDX-1140, Poly ICLC, Radiation Therapy, Recombinant Flt3 Ligand, Pembrolizumab
Keywords
High-grade bone sarcoma, High-grade soft tissue sarcoma, Basal Cell Carcinoma
Medical subject headings
Breast Neoplasms, Melanoma, Carcinoma, Merkel Cell, Sarcoma, Bone Neoplasms, Osteosarcoma, Carcinoma, Basal Cell

What participants receive

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

  • Anti-CD40 Agonist Monoclonal Antibody CDX-1140Biological

    Also called Agonist CD40 Antibody CDX-1140, Anti-CD40 Agonistic Monoclonal Antibody CDX-1140, CDX 1140, CDX-1140

    Given IT

  • Poly ICLCDrug

    Also called Hiltonol, Poly I:Poly C with Poly-L-Lysine Stabilizer, poly-ICLC, PolyI:PolyC with Poly-L-Lysine Stabilizer

    Given IT

  • Radiation TherapyRadiation

    Also called Cancer Radiotherapy, Irradiate, Irradiated, Irradiation

    Undergo radiation therapy

  • Recombinant Flt3 LigandBiological

    Also called CDX-301, FLT 3 Ligand, FLT3 Ligand, Flt3-Ligand

    Given IT

  • PembrolizumabDrug

    Also called Keytruda

    Given IV

  • TocilizumabDrug

    Also called Actemra

    Given SC

Study groups in NCT04616248
Study groupRoleWhat they receive
Cohort A (immunomodulators, radiation therapy)ExperimentalPatients receive recombinant Flt3 ligand IT on days 1-5 and undergo radiation therapy on day 8 or 9. Patients also receive agonistic anti-CD40 monoclonal antibody CDX-1140 IT and Poly-ICLC IT on day 9 or 10. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Anti-CD40 Agonist Monoclonal Antibody CDX-1140; Drug: Poly ICLC; Radiation: Radiation Therapy; Biological: Recombinant Flt3 Ligand
Cohort B (immunomodulators, radiation therapy)ExperimentalPatients receive recombinant Flt3 ligand IT on days 1-5 and also receive pembrolizumab (IV), tocilizumab (SC) as well as undergo radiation therapy on day 8 or 9. Patients also receive agonistic anti-CD40 monoclonal antibody IT and IV over 90 minutes and Poly-ICLC IT on day 9 or 10. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Anti-CD40 Agonist Monoclonal Antibody CDX-1140; Drug: Poly ICLC; Radiation: Radiation Therapy; Biological: Recombinant Flt3 Ligand; Drug: Pembrolizumab; Drug: Tocilizumab

What is being measured

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

  1. Incidence of adverse events

    Measured: Up to 30 days

  2. Maximum tolerated dose or maximum administered dose

    The dose limiting toxicity rate will be estimated by cohort and dose-level (if appropriate) using 90% confidence intervals obtained by Jeffrey's prior method.

    Measured: Up to 30 days

Secondary outcomes (4)

  1. Changes in Immune signatures in the tumor microenvironment

    Will examine changes in the immune biomarkers levels from baseline to end of treatment

    Measured: Baseline up to 2 years

  2. Changes in the levels of infiltrating CD4+ and CD8+ T cells

    Will examine changes in the levels of infiltrating CD4+ and CD8+ T cells and their proteomic, genomic and transcriptomic signatures in the tumor microenvironment. The immune biomarker levels are treated as continuous variables and will be summarized in the overall sample and within treatment-arm by time-point using the mean and standard error, and graphically using dot-plots.

    Measured: Baseline up to 2 years

  3. Changes in the levels of infiltrating myeloid cell subsets

    Will examine changes in the levels of infiltrating myeloid cell subsets including dendritic cells (DCs), macrophages, and monocytes, and their proteomic, genomic and transcriptomic signatures in the tumor microenvironment. The immune biomarker levels are treated as continuous variables and will be summarized in the overall sample and within treatment-arm by time-point using the mean and standard error, and graphically using dot-plots.

    Measured: Baseline up to 2 years

  4. Changes in the levels of PD-L1 expression

    Will examine changes in the levels of PD-L1 expression within both neoplastic and nonneoplastic stromal elements of the tumor microenvironment. The immune biomarker levels are treated as continuous variables and will be summarized in the overall sample and within treatment-arm by time-point using the mean and standard error, and graphically using dot-plots.

    Measured: Baseline up to 2 years

Timeline

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

  1. First posted4 Nov 2020
  2. Study start9 Jan 2023
  3. Primary completion9 Jan 2027 (estimated)
  4. Study completion9 Jan 2028 (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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04616248
Sponsor's protocol ID
1B-22-2
Other IDs
NCI-2022-07303, 1B-22-2
Status last verified
Jun 2026
First submitted
26 Oct 2020
Last updated
18 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anti-CD40 Agonist Monoclonal Antibody CDX-1140, Poly ICLC and Radiation Therapy in people with Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Breast Carcinoma, run by University of Southern California at 2 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 22 inclusion and 28 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 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

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?

Incidence of adverse events (time frame: Up to 30 days). The study lists 2 primary outcomes in all. 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 NCT04616248.

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 18 Jun 2026.

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