402MO - Final results of the CARACAS study: Randomized phase II trial of avelumab alone or with cetuximab for unresectable, locally advanced or metastatic squamous cell anal carcinoma progressed to at least one line of treatment

Background

Advanced squamous cell anal carcinoma (advSCAC) is a rare disease with no standard therapies beyond first line currently available. Case series and phase I and II prospective studies have documented respectively promising activity of the anti-EGFR cetuximab (CET) and of immunotherapy in chemorefractory advSCAC. In this study, we aimed to evaluate activity and safety of avelumab (AVE) alone or in combination with CET in pretreated advSCAC.

Methods

This was an open-label, “pick the winner”, prospective, multicenter randomized phase 2 trial (NCT03944252). Patients (pts) with mSCAC who had progressed after at least one line of treatment were randomized 1:1 to receive either AVE (arm A) or AVE+CET (arm B). A Simon’s two-stage Mini-Max design was used. Primary endpoint was overall response rate (ORR). The null hypothesis that the true response rate was 5% (P = 0,05) was tested against the alternative of a true response rate of 20% (P1= 0,20) in each arm. Type I error rate was set at 0,05. Secondary endpoints were progression free survival (PFS), overall survival (OS) and safety. No formal comparison was allowed between the two arms.

Results

60 pts were enrolled, 30 in each arm. Median age was 63 years; M/F distribution was 19/41. All baseline characteristics were well balanced between the two arms. At a median follow up of 11 months, 5 patients out of 30 showed PR in arm B, reaching the primary endpoint. ORR was 10% (95% CI 2.5 - 27) and 17% (95% CI 6.3 – 34,1) in arm A and B, respectively; Disease control rate (DCR) was 50% (95% CI 35.3 – 71.3) in arm A and 57% (95% CI 42.4 – 77.6) in arm B. Median PFS was 2.05 months (95% CI 1.84 – 5.52) in arm A and 3.88 months (95% CI 2.07 – 6.14) in arm B. Median OS data were not yet mature. The most common treatment related adverse event (TRAE) were fatigue in Arm A (17%) and skin and subcutaneous disorders in arm B (87%); 2 patients (7%) in arm B permanently interrupted the treatment due to TRAE; no permanent interruptions due to TRAE were observed in arm A.

Conclusions

The CARACAS Study met its primary endpoint in patients receiving AVE+CET (arm B), with promising activity of dual EGFR and PD-L1 blockade in advSCAC deserving further investigation. A favourable safety profile was observed in both of the study arms.

Clinical trial identification

NCT03944252.

Editorial acknowledgement

Legal entity responsible for the study

Veneto Institute of Oncology IOV – IRCCS.

Funding

Veneto Institute of Oncology IOV - IRCCS; GONO - Gruppo Oncologico Nord Ovest; Pharmaceutical/Biotech Company: Merck Serono.

Disclosure

S. Lonardi: Advisory/Consultancy: Amgen; Lilly; Merck Serono; Servier; Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Lilly; Merck Serono; Roche; Servier; Research grant/Funding (self): Amgen; Merck Serono;. F. Pietrantonio: Advisory/Consultancy: Amgen; Bayer; Lilly; Merck Serono; Roche; Sanofi; Servier; Research grant/Funding (self): Bristol-Myers Squibb. V. Formica: Honoraria (self): Amgen; Servier. M. Scartozzi: Advisory/Consultancy: Amgen; Bayer; Bristol-Myers Squibb; Celgene; Eisai; Merck Serono; Sanofi; Speaker Bureau/Expert testimony: Amgen; Bayer; Eisai; Merck Serono; Roche/Genentech; Servier; Research grant/Funding (self), Research grant/Funding (institution): Bayer; Celgene (Inst); Merck Serono (Inst); Merck Sharp & Dohme (Inst); Sanofi (Inst); Travel/Accommodation/Expenses: Celgene; Merck Serono; Servier. V. Zagonel: Advisory/Consultancy: Bristol-Myers Squibb; Merck; Speaker Bureau/Expert testimony: Astellas Pharma; AstraZeneca; Bayer; Bristol-Myers Squibb; Lilly; Roche; Servier laboratories Ltd; Travel/Accommodation/Expenses: Bayer; Roche; Servier laboratories Ltd. All other authors have declared no conflicts of interest.