Enrollment Begins in Phase 2 Trial of Rintatolimod in PD-1/PD-L1 Resistant Melanoma

Enrollment has begun for a phase 2 study of a polarized dendritic cell vaccine plus interferon alpha-2b, rintatolimod, and celecoxib in melanoma with PD1/PD-L1-resistance.

A phase 2 study examining a polarized dendritic cell (aDC1) vaccine in combination with interferon alpha-2b, rintatolimod (ampligen), and celecoxib (Celebrex), in patients with primary PD-1/PD-L1 resistant melanoma has begun enrolling patients, according to AIM ImmunoTech Inc.1

“The start of this NCI-funded clinical trial marks an important milestone for our Melanoma R&D program. Despite recent successes of immune checkpoint inhibitors in advanced-stage disease, only a minority of treated melanoma patients have a durable benefit, reinforcing the need to develop second-line therapies that are effective against checkpoint-refractory disease,” said Thomas K. Equels, chief executive officer of AIM ImmunoTech Inc, in the press release. “Based on the data seen to-date, we believe Ampligen, in combination with Roswell’s polarized dendritic cell vaccine plus interferon, has an opportunity to fill this gap and potentially provide clinical benefit to melanoma patients in need.”

Rintatolimod is being developed as a combinational therapy for the treatment of a variety of solid tumor types and is currently being evaluated in multiple clinical trials.

In the single-arm, phase 2 study (NCT04093323), investigators will evaluate the aDC1 vaccine in combination with the tumor-selective chemokine modulation made up of interferon alpha 2b, rintatolimod, and celecoxib.2

Up to 24 patients aged 18 years and older with immuno-oncology-refractory melanoma with primary PD1-resistance and who is HLA-A2-positive will be enrolled in the trial. Patients must have 1 or more tumor site amenable to core needle biopsy that is not the site of disease used to measure antitumor response, measurable disease based on RECIST 1.1 criteria, and an ECOG performance status of 0-2.

Those enrolled will be on active experimental treatment for 12 weeks. Patients receive recombinant interferon alpha-2 intravenously (IV) over 30 minutes, rintatolimod IV over 2.5 hours, and celecoxib orally twice a day on days 1-3. When cycle 2 starts, patients also will receive alpha-type-1 polarized dendritic cells intradermally on day 1.

Treatment will repeat every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. At week 12, patients with progressive disease may switch to ipilimumab with or without a PD-1/PD-L1 inhibitor and patients who have either a complete response, partial response, or stable disease may switch to a PD-1/PD-L1 inhibitor or best alternative care.

After completion of study treatment, patients will continue to be monitored for progression-free survival (PFS) and overall survival (OS) within standard care visits that take place every 3 months for up to 2 years.

The primary endpoint of the study is objective response rate (ORR) at 12 weeks and durable ORR. Secondary end points of the study include immune-related PFS, OS, change in density of CD8 positive cytotoxic T cells, and change in density of molecular biomarkers.

The study is actively recruiting in New York and has an estimated study completion date of August 22, 2025.

“We are interested in further exploring the potential of rintatolimod for the treatment of refractory melanoma and appreciate AIM’s participation and collaboration in this study,” said Pawel Kalinski, MD, PhD, Roswell Park Chair of Immunology, in the press release. “Based on the pre-clinical data demonstrated, we believe that combining our vaccine approach with the rintatolimod-based modulation of the tumor microenvironment in a first-in-human trial has potential for converting checkpoint PD1-resistant ‘cold’ melanomas into PD1-sensitive ones. We look forward to getting this study underway and remain dedicated to evaluating the potential effectiveness of rintatolimod for this application.”
  1. AIM mmunoTech and study collaborator roswell park commence enrollment in an NCI-funded phase 2 clinical trial evaluating ampligen® (rintatolimod) in primary PD-1/PD-L1 resistant melanoma. News release. Aim ImmunoTech Inc. August 30, 2022. Accessed September 2, 2022. https://bit.ly/3RacljA
  2. Polarized dendritic cell (aDC1) vaccine, interferon alpha-2, rintatolimod, and celecoxib for the treatment of HLA-A2+ refractory melanoma. ClinicalTrials.gov. Updated August 23, 2022. Accessed September 2, 2022. https://www.clinicaltrials.gov/ct2/show/NCT04093323