Experience of patients with HIV and squamous cell carcinoma of the anal canal (SCAC) treated with retifanlimab.

3521 Background: People living with HIV (PLHIV) usually have more advanced cancer at diagnosis and a higher cancer-related mortality, posing a significant burden on health care. However, clinical studies often exclude cancer patients with HIV, thereby limiting access to therapies for this patient population. PLHIV have a 25- to 35-fold higher chance of being diagnosed with SCAC than individuals who are HIV negative. We therefore evaluated safety and efficacy of retifanlimab in PLHIV with SCAC. Methods: The study designs for POD1UM-202 (NCT03597295) and POD1UM-303/InterAACT-2 (NCT04472429) have previously been described. Both trials permitted PLHIV to enroll if CD4+ count was ≥200/μL with an undetectable viral load per standard of care assay, and who did not experience any HIV-related opportunistic infection for ≥4 weeks prior to study enrollment. Patients continued to receive antiretroviral therapy (ART/HAART) without interruption or dose reduction. HIV viral load and CD4+ cell count was assessed every 8 weeks during the studies and could be reduced to every 6 months during safety and disease follow-up. Results: Patient and disease characteristics were similar among PLHIV and the overall study populations. Among the 20 patients with HIV enrolled in these SCAC trials, median age was 58 years, 70% (n = 14) were male, and 80% (n = 16) were White. Forty-five percent (n = 9) of patients received retifanlimab and 30% (n = 6) received retifanlimab with platinum-based chemotherapy, whereas the remaining 5 patients were assigned to placebo plus chemotherapy. During these studies, no patient experienced a sustained drop in CD4+ T-cell counts or increase in HIV viral load of clinical significance. No treatment-emergent opportunistic infections were recorded. Immune-related adverse events (irAEs) and grade ≥3 irAEs were consistent with the non-HIV population. Objective response rates were 22% (2/9) with retifanlimab in second-line and 67% (4/6) with retifanlimab and chemotherapy in first-line (previously untreated). Patient-reported outcomes showed no negative impact and based on Quality-of-Life Questionnaire for Anal Cancer, good scores for bowel function, sexual, and symptom domains were maintained. Retifanlimab pharmacokinetics was independent of HIV status and not impacted by the HAART required for ongoing HIV management. Conclusions: Among PLHIV and advanced SCAC who received treatment, retifanlimab showed significant clinical activity with efficacy qualitatively similar to patients without HIV and no excess toxicity or reduced HIV control. The analysis indicates that retifanlimab is generally safe for PLHIV and SCAC and also supports inclusion of HIV-positive patients in other immunotherapy trials. The favorable outcomes in PLHIV are encouraging because infection with HIV is among the most important risk factors for SCAC. Clinical trial information: NCT03597295 and NCT04472429 .