In Situ Immunomodulation With CDX-301, Radiation Therapy, CDX-1140 and Poly-ICLC in Patients w/ Unresectable and Metastatic Solid Tumors
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
2 other identifiers
interventional
14
1 country
2
Brief 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, 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jan 2023
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 26, 2020
CompletedFirst Posted
Study publicly available on registry
November 4, 2020
CompletedStudy Start
First participant enrolled
January 9, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 9, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 9, 2028
January 7, 2026
January 1, 2026
4 years
October 26, 2020
January 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events
Up to 30 days
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.
Up to 30 days
Secondary Outcomes (4)
Changes in Immune signatures in the tumor microenvironment
Baseline up to 2 years
Changes in the levels of infiltrating CD4+ and CD8+ T cells
Baseline up to 2 years
Changes in the levels of infiltrating myeloid cell subsets
Baseline up to 2 years
Changes in the levels of PD-L1 expression
Baseline up to 2 years
Other Outcomes (4)
Overall response rate (ORR)
Up to 2 years
Overall survival
From treatment initiation until death due to any cause (event) or last follow-up, assessed up to 2 years
Progression free survival
From treatment initiation until disease progression, death due to disease (events), or last follow-up, assessed at 1 year
- +1 more other outcomes
Study Arms (2)
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.
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.
Interventions
Given IT
Given IT
Undergo radiation therapy
Given IT
Eligibility Criteria
You may qualify if:
- 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.
- 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)
- +7 more criteria
You may not qualify if:
- 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).
- 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.
- 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.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Fumito Ito, MD
University of Southern California
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 26, 2020
First Posted
November 4, 2020
Study Start
January 9, 2023
Primary Completion (Estimated)
January 9, 2027
Study Completion (Estimated)
January 9, 2028
Last Updated
January 7, 2026
Record last verified: 2026-01