Combination treatment for certain cancers using radiation and immune therapies

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

This study is testing a new combination of radiation and immune therapies to see if it can help people with non-Hodgkin's lymphoma, metastatic breast cancer, and head and neck cancer fight their disease better.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Icahn School of Medicine at Mount Sinai (Academic / other)
• Drugs / interventions: pembrolizumab, chemotherapy, radiation, prednisone
• Locations: 1 site (New York, New York)
• Trial ID: NCT03789097 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates a combination of four therapies to treat patients with non-Hodgkin's lymphoma, metastatic breast cancer, and head and neck squamous cell carcinoma. The approach includes localized radiation to a tumor site, administration of an immune cell growth factor (Flt3L), and the use of an immune checkpoint inhibitor (pembrolizumab) alongside a Toll-like receptor ligand (poly-ICLC). The study is conducted in two phases, with Phase 1 focusing on safety and toxicity assessment, followed by Phase 2 to further evaluate efficacy. The trial aims to enhance the immune response against cancer cells while minimizing side effects.

Who should consider this trial

Good fit: Ideal candidates include individuals with pathologically confirmed non-Hodgkin's lymphoma, metastatic breast cancer, or head and neck squamous cell carcinoma.

Not a fit: Patients requiring immediate treatment or those with certain aggressive lymphoma subtypes may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with specific types of cancer by enhancing their immune response.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, but this specific combination is novel.

Eligibility criteria

Inclusion Criteria:

* Have pathologically confirmed iNHL, MBC or HNSCC
* Lymphoma subtypes that may be enrolled include small lymphocytic lymphoma

Exclusion Criteria:

* Is currently participating and receiving an investigational therapy (not standard therapies) or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of treatment.
* Any patients that require immediate treatment or cytoreduction are excluded. Note: This is applicable for iNHL, MBC, and HNSCC populations.
* Any patient with transformed lymphoma, or patients with grade 3A follicular lymphoma are excluded.
* MZL patients with gastric MALT lymphomas with disease localized to the stomach are excluded, and any patient with disease in a site where injection is determined to be high risk.
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
* Hypersensitivity to pembrolizumab, poly-ICLC, Flt3L or any of their excipients.
* Has had a prior anti-cancer monoclonal antibody (mAb) within 28 days prior to study D22 (First dose of pembrolizumab) or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to agents administered more than 28 days before initiation of in situ vaccine protocol.
* Has had prior chemotherapy, targeted small molecule therapy, or RT therapy within 14 days prior to study D0 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to a previously administered agent. Note: Patients with chronic ≤ Grade 2 AEs such as neuropathy are an exception to this criterion and may qualify for the study.
* Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
* Has known active central nervous system metastases, leptomeningeal disease and/or lymphomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include leptomeningeal disease or lymphomatous meningitis, which are excluded regardless of clinical stability.
* Has active autoimmune disease that has required systemic treatment in the past 1 year (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 systemic treatment. Patients on chronic steroids (more than 4 weeks at stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy at time of enrollment in trial.
* Has a known additional 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 or anal cancer, prostate cancer on stable dose of hormonal therapy without rising PSA.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
* Has known psychiatric or substance abuse disorders that investigator believes would interfere with cooperation with the requirements of the trial.
* 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 (roughly two and a half years after enrollment).
* HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen.
* Has known active Hepatitis B (e.g., HBV detected by PCR) or active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
* History of allogeneic hematopoietic cell transplantation or solid organ transplantation.
* Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
* Patients with grade 3B follicular lymphoma

Where this trial is running

New York, New York

• Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Joshua Brody, MD — Icahn School of Medicine at Mount Sinai
• Study coordinator: Martine Van Voorthuysen

Conditions Non-Hodgkin's Lymphoma; Metastatic Breast Cancer; Head and Neck Squamous Cell Carcinoma; Radiation; Poly-ICLC; Pembrolizumab; Lymphoma; Breast Cancer