Roswell Park Comprehensive Cancer Center, Buffalo, NY
Karan Jatwani , Suresh Kalathil , Ronald Slomba , Bailey Farmer , Kristopher Attwood , Arya Mariam Roy , Prashant Singh , Eric Kauffman , Dharmesh Gopalakrishnan , Saby George , Ellis Glenn Levine , Khurshid Guru , Pawel Kalinski , Gurkamal S. Chatta
Background: Most patients with high or very high risk localized prostate cancer (PCa) experience disease recurrence after radical prostatectomy (RP). A high intra-tumoral CD8+ T lymphocyte density is associated with improved survival post-RP,1 suggesting possible clinical benefit from neoadjuvant chemokine modulation (CKM).2,3 We present the interim results of a three-arm, phase II trial where patients with localized PCa scheduled to undergo RP were randomized in 1:1:1 ratio to a 2-week regimen of neoadjuvant CKM triplet (Arm A: rintatolimod + aspirin + IFN-α: “Complete CKM regimen”) vs CKM doublet (Arm B: rintatolimod + aspirin) vs no CKM (Arm C). Methods: Thirty patients (10 per arm) are to be enrolled to assess CD8+ T cell density in the RP specimen as the primary endpoint. Pathological and PSA responses, surgical margin positivity, and safety/toxicity of the CKM combinations represent secondary endpoints. Correlative blood studies analyzed the pre- vs post-CKM changes in Granzyme B (GrB; marker of effector/cytotoxic function in CD8+ T cells and FoxP3 (Treg marker) in CD4+ T cells. Results: The trial has enrolled 11 patients thus far (N=5 Arm A, 3 Arm B, 3 Arm C). There were no clinicopathological differences between the groups. Eight patients (on Arms A and B) were analyzed for changes in cytotoxic T cell numbers (CTL-D: GrB+CD8+ T-cells) in the blood. In Arm A, the mean pre-CKM CTL-D was 35.5% (±23.2%) and post-CKM was 47.7% (± 32.5%), while in Arm B, respectively, 37.9% (±22.2%) vs 37.1% (± 21.6%). These changes were reflected in the increased CTL/Treg markers in the post-treatment samples of patients on Arm A. These data indicate the ability of the “complete CKM regimen” (Arm A) to selectively enhance the CTL effector function in circulating CD8+ T cells, without enhancing the Treg markers. CKM regimen was well tolerated with no Grade 3 or above adverse events (AEs). Conclusions: In this interim analysis, treatment in all arms was feasible and safe. CTL-D and CTL-D/Treg in Arm A (“complete CKM”) shows an increasing trend over the course of CKM treatment. The levels of CTL-D in the resected prostate tissues are being currently evaluated. The study continues recruiting patients. 1. Yang, Y et al (PMID 33085799). 2. Muthuswamy, R et al (PMID 27199259). 3. Theodoraki, MN et al (PMID 29853604). Clinical trial information: NCT03899987.
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Abstract Disclosures
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