Vaccination With Flt3L, Radiation, and Poly-ICLC

Metastatic Breast Cancer Clinical Trial

Official title: In Situ Vaccination With Flt3L, Radiation, and Poly-ICLC Combined With Pembrolizumab in Patients With Non-Hodgkin's Lymphoma, Metastatic Breast Cancer, and Head and Neck Squamous Cell Carcinoma

Status Recruiting

Clinical Trial Summary

This is a combination of 4 therapies, three of which are used to treat a single "target site" of your cancer (such as a lymph node or a single tumor), and the 4th is given directly into the blood stream (intravenous or "IV").

1. Radiation: The target site --lymph node or tumor (the one what will be injected) --will get two small treatments of radiation. Radiation is often times used to shrink and kill tumors in patients with certain types of lymphoma, breast cancer and head and neck cancer, however, the dose of radiation that you will receive --one dose on day one of the clinical trial and one dose on day two --is 10 to 20 time less radiation that you would receive for treatment of these cancers.

2. Flt3L/CDX-301 is an immune cell growth factor, similar to white blood cell growth factors (Neupogen or Neulasta) or red blood cell growth factors (EPO or Epogen) that you may have received to help protect your blood cells previously. Flt3L causes your body to make more immune cells, specifically a type of immune cell called "dendritic cells".

3. Poly-ICLC is an immune cell activating factor. Its function is to turn on the immune cells that have been brought to the tumor by Flt3L.

4. Pembrolizumab is an antibody (a type of human protein) that is being tested to see if it will allow the body's immune system to kill your tumor cells. Pembrolizumab is approved for use by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with many different types of cancer including head and neck cancer. Pembrolizumab is not FDA approved to treat patients with non-Hodgkin's lymphoma or metastatic breast cancer, as it has not been effective at treating these cancers when used alone. While most people do not have immediate side effects when this medication is given, it has the ability to cause side effects for.

Clinical Trial Description

Phase 1 and Phase 2 will occur sequentially:

Phase 1 is the preliminary safety assessment portion of the study, which will follow a modified 3 + 3 design to assess toxicity. The trial would be held for review should there be more than 1 dose-limiting toxicity (DLT) observed within the first 3-6 patients. The toxicity of the in situ vaccine without pembrolizumab (ongoing and previous trials) has been minimal, limited to transient febrile response to the intratumoral Toll-like receptor (TLR) ligand poly-ICLC, typically resolving with oral acetaminophen. As such, the primary objective of Phase 1 is to assess the safety of the addition of pembrolizumab to this in situ vaccine protocol. In Phase 1, patients will only be enrolled at the lead institution (Mount Sinai). After enrollment of the initial 3 patients, enrollment will pause until all three patients have completed cycle 1 of pembrolizumab (DLT evaluation window is 63 days from initiation of in situ vaccine). During the pause, new patients may be consented and screened, but not initiated on therapy. If 1 or no DLTs are observed in the first 3 patients, an additional 3 patients will be enrolled. The regimen will be considered safe (in order to progress to Phase 2) if no more than 1 out of 6 patients experience a DLT. If two or more DLTs are observed at any point in Phase 1 then accrual will be stopped for protocol review by Data Safety Monitoring Board, PIs and sponsor for possibility of protocol amendment.

Phase 2 will follow a Simon's two-stage design. This Phase will proceed only if toxicity is acceptable as determined in Phase 1.

Phase 1/2 design: Patients will be enrolled concurrently into three independent cohorts, with patients from Phase 1 evaluated within their subsequent disease-specific cohorts. iNHL, MBC and HNSCC often have peripherally accessible tumors amenable to intratumoral injection, and have all had relatively modest responses to single-agent checkpoint blockade, so are good candidates for this novel combination. Patients will be enrolled regardless of the PD-L1 staining of their tumor. We will also enroll patients previously exposed to PD-1/PD-L1 targeted therapies either on a clinical trial or as standard of care (as for HNSCC).

Cohort A: iNHL including but not limited to chronic lymphocytic leukemia (CLL/SLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). This cohort excludes patients with diffuse large B cell lymphoma (DLBCL) and any other lymphoma determined to be progressing rapidly by investigator (PI or site PI).

Cohort B: MBC with peripherally palpable disease amenable to intratumoral injection.

Cohort C: HNSCC with peripherally palpable disease amenable to intratumoral injection.

Stage 1: Seven patients will be evaluated in Stage 1 of Phase 2 in each disease-specific cohort, inclusive of patients enrolled in Phase 1. If no patient in a cohort achieves a response, the study in that cohort will close due to a lack of efficacy. The first seven patients in each histology will only be enrolled at Mount Sinai.

Stage 2: If one or more responses are seen in Stage 1, enrollment of an additional 12 patients for Cohorts A and B or 11 patients for Cohort C will proceed. These cohorts may be also be enrolled at collaborator sites (to be determined).

• Cohorts A or B: If at least three out of the 19 patients achieve a response, the intervention will be considered promising and worthy of further investigation.

• Cohort C: If at least four out of the 18 patients achieve a response, the intervention will be considered promising and worthy of further investigation. ;

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma
• Lymphoma
• Lymphoma, Non-Hodgkin
• Metastatic Breast Cancer
• Non-Hodgkin's Lymphoma
• Squamous Cell Carcinoma of Head and Neck

• NCT number: NCT03789097
• Study type: Interventional
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Martine Van Voorthuysen
• Phone: (212) 824-7822
• Email: Martine.VanVoorthuysen@mssm.edu
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 5, 2019
• Completion date: March 2025