Atezolizumab plus tiragolumab in combination with chemoradiotherapy in localized squamous cell carcinoma of the anal canal: TIRANUS (GEMCAD-2103) trial.

Abstract

11 Background: Radical chemoradiotherapy (CRT) is the standard of care in patients (pts) with localized squamous cell carcinoma of anal canal (SCAC). However, approximately 30% of pts fail to achieve a complete clinical response (CCR) and require salvage surgery. Overexpression of poliovirus receptor (PVR) and PD-L1 in SCAC, along with the potential of CRT to enhance antigen presentation, provides a strong rationale for combining CRT with immunotherapy. This trial evaluates whether adding atezolizumab (A; anti–PD-L1) and tiragolumab (T; anti–TIGIT) to CRT improves response rates. Methods: TIRANUS is a Phase II, single-arm, open-label, multicenter clinical trial. Pts ≥18 years of age with confirmed diagnosis of localized SCAC eligible for CRT. Pts candidates for curative surgery or with contraindications to study treatment were excluded. Treatment consisted of standard CRT plus A (1200mg) and T (600 mg) for 8 cycles (Q3W). The inclusion of 45 pts was planned to obtain a CCR precision estimation of 85% ±10.4%. The primary endpoint was CCR rate at week 26, defined as radiologic CR by RECIST 1.1 and/or pathological CR. Secondary endpoints included overall CCR and colostomy-free survival (CFS). Results: Between March 23 to October 24, 46 pts were enrolled. The median age was 58 years (range: 36-80), 72% were females. 61% had T3-4 tumors, 74% had nodal involvement, and 88% were HPV-positive. At week 26, 44 pts were evaluable (2 excluded due to withdrawal/protocol deviation). The CCR rate at week 26 was 67.4% (95% CI: 51.5-80.9). With a median follow-up of 15 months, the overall CCR was 79,6% (95% CI: 64.7–90.2), including 3 pts with radiological partial response and 1 pts with stable disease who had no presence of residual tumor cells after salvage surgery. 3 pts required colostomy. The CFS rate was 93.2%. Study treatment was completed as scheduled in 84.8% of pts, while 13.2% discontinued due to unacceptable toxicity. The most common any grade adverse events were asthenia (50%), diarrhoea (47,8%), and nausea (43,5.0%) and G3-G4 grade, neutropenia (10,9%) and diarrhoea (8,7%). Most frequent G1-G2 immune–mediated reactions were pruritus (21.7%), infusion related reaction (8.7%), arthralgia (8,7%), mucositis (6.5%) and skin toxicity (6.5%), and G3-4 neutropenia (6.5%). Conclusions: The addition of A and T to CRT was feasible and generally well tolerated. Further follow-up is warranted to confirm efficacy and assess long-term benefit in reducing the need for surgical rescue. Clinical trial information: NCT05661188 .