Trials / Active Not Recruiting

Active Not RecruitingNCT04616248

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

Status: Active Not Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 14 (actual)

Sponsor: University of Southern California · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. 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: I. 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: I. 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.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Anti-CD40 Agonist Monoclonal Antibody CDX-1140	Given IT
DRUG	Poly ICLC	Given IT
RADIATION	Radiation Therapy	Undergo radiation therapy
BIOLOGICAL	Recombinant Flt3 Ligand	Given IT
DRUG	Pembrolizumab	Given IV
DRUG	Tocilizumab	Given SC

Timeline

Start date: 2023-01-09
Primary completion: 2027-01-09
Completion: 2028-01-09
First posted: 2020-11-04
Last updated: 2026-01-07

Locations

2 sites across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04616248. Inclusion in this directory is not an endorsement.