AIM ImmunoTech Inc (NYSE:AIM) presented positive data from its ongoing Phase 2a clinical study at the Roswell Park Comprehensive Cancer Center evaluating its flagship drug Ampligen (rintatolimod) as a component of a Chemokine Modulatory (CKM) regimen for the treatment of colorectal cancer metastatic to the liver at the six-day annual meeting of the American Association for Cancer Research (AACR), which kicked off on April 8, in New Orleans, Louisiana.
The Ocala, Florida-based immuno-pharma company said the research was led by Roswell Park medical oncologist Sarbajit Mukherjee, in collaboration with senior investigator Pawel Kalinski, who is the chair of Immunology at Roswell Park.
AIM said based on preclinical data showing the prognostic value of intratumoral CD8+ T cell (CTL) in colorectal cancer outcomes, it was hypothesized that “systemic infusion” of the combination of IFNα-2b with Ampligen (selective TLR3 ligand for IV use) could “reprogram” the local balance between the CTL and regulatory T cell (Treg)-attracting chemokines and the resulting patterns of immune infiltrates in liver tumors.
The early Phase 2a trial studied how well celecoxib, recombinant interferon alfa-2b, and Ampligen work in treating patients with colorectal cancer that has spread to the liver.
The study was designed on the basis that celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth; while recombinant interferon alfa-2b is a substance that can improve the body's natural response and may interfere with the growth of tumor cells; and AIM’s drug Ampligen may stimulate the immune system. Therefore, giving celecoxib, recombinant interferon alfa-2b, and Ampligen together may help “reprogram the tumor microenvironment and make the tumors more responsive to immune therapy,” said the company.
The study selected patients with recurrent/metastatic colorectal cancer with unresectable liver metastases amenable to biopsy. Patients had prior treatment (Rx) with fluoropyrimidine, irinotecan, oxaliplatin, and an anti-EGFR targeted therapy (if RAS wt), or contra-indication to such.
According to AIM, the patients received IFNα-2b IV (20 million units/m2 IV daily) and Ampligen (200 mg IV daily) plus oral celecoxib (200 mg twice daily) on days 1, 2, 3, 8, 9, 10, 15, 16, and 17. Response assessment was done through liver biopsies (pre-Rx and on day 24 ± 4 days) and CT imaging (RECIST v1.1) on Day 46.
The primary endpoint was the change in CD8+ T-cells before Rx, with that seen post-Rx. With a sample size of N=12 evaluable points, the study design had a 90% power to detect a 0.77 standard deviation increase (pre- to post Rx) at a significance level of 0.1.
AIM revealed that 19 patients with microsatellite stable (MSS) colorectal cancer were enrolled in the study between April 2018 and October 2020, and 12 were evaluable for the primary endpoint.
“The primary endpoint of this study, a significant increase in CD8a expression post-treatment, along with increases in CTL-attracting chemokines coupled with a decrease in a key Treg/MDSC attractant indicate a positive immune effect on the tumor microenvironment and suggest this CKM approach has the potential to increase tumor responses to checkpoint inhibitors,” said medical expert David R. Strayer, MD.
Here are the key findings of the study:
- The study's primary endpoint was met, evidenced by increased CD8a expression post-treatment (p=0.046);
- Saw increase in the CD8a/CD4 (p=0.03), CD8a/FOXP3 (p<0.01) and GZMB/FOXP3 (p<0.01) ratios;
- No tumor responses were seen, and the treatment was well tolerated.
Contact the author Uttara Choudhury at uttara@proactiveinvestors.com
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