Camrelizumab plus apatinib for previously treated advanced adrenocortical carcinoma: A single-arm, open-label, phase 2 trial.

4511 Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with dismal prognosis. Therapeutic options for patients with advanced ACC after failure of standard treatments are limited. The clinical benefit of single-agent immunotherapy as second-line therapy was still unsatisfactory. Methods: This was an investigator-initiated, prospective, single-arm, open-label, phase 2 trial and conducted at a single medical center. Patients were eligible for inclusion if they were aged at least 18 years; were pathologically diagnosed as unresectable or metastatic ACC; had failed first-line therapy; had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; had at least one measurable lesion; and had adequate organ function. The key exclusion criteria included a history of treatment with immunotherapy, anti-angiogenic small molecule TKIs, or anti-angiogenic monoclonal antibodies; a history of uncontrolled hypertension; and a history of an autoimmune condition requiring systemic therapy. All study participants received camrelizumab 200 mg intravenously on the first day of each 3 week cycle, combined with apatinib 250 mg orally once per day until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR), defined as the proportion of participants with complete response (CR) or partial response (PR) per RECIST (version 1.1). Results: A total of 21 patients with advanced ACC received at least one dose of camrelizumab and apatinib. ORR was 52% (95% CI, 30 to 74), and the disease control rate was 95% (95% CI, 84 to 100), superior to PD-1 inhibitor monotherapy and first-line standard therapy. The median PFS was 12.6 months (95% CI, 8.4 to 20.9), and the median OS was 20.9 months (95% CI, 11.0 to 20.9). The most common grade 3—4 treatment-related adverse events were alanine aminotransferase elevation (28.6%), aspartate aminotransferase elevation (23.8%) and lymphopenia (23.8%). Our exploratory analysis showed higher peripheral blood CXCR3+CD8+ T cell abundance, lower immunosuppressive CD4+ T cell abundance, and higher overlap of clonotypes between tumor-infiltrating T cells and circulating T cells, likely related to preferable response to camrelizumab plus apatinib therapy. Conclusions: In conclusion, the combination of camrelizumab with apatinib showed promising activity and acceptable toxicity in advanced ACC patients who failed previous lines of therapy. Pre-treatment peripheral blood immune cell subsets could be regarded as potential predictors of efficacy. Given the promising clinical activity, the potential of camrelizumab with apatinib as first-line therapy for advanced ACC need further evaluated. Clinical trial information: NCT04318730 .