Background: Probody™ therapeutics are novel, fully recombinant antibody prodrugs designed to remain relatively inactive in healthy tissue and to be specifically activated by proteases in the tumor microenvironment. In this way, Probody therapeutics may broaden the therapeutic window for effective but potentially toxic anticancer agents. CX-072 is a Probody therapeutic directed against programmed death-ligand 1 (PD-L1) for the treatment of cancer patients. In a first-in-human, open-label, multicenter, dose-escalation, 3+3 design, phase 1-2 study, PROCLAIM-CX-072 (PRObody CLinical Assessment In Man) (NCT03013491), 22 patients were enrolled in the phase 1 dose escalation portion. Twenty patients were evaluable per RECIST v1.1. Three patients had confirmed partial response (15%), including a 39-year-old woman with stage IV triple negative breast cancer (TNBC) treated with 10 mg/kg CX-072 monotherapy whose disease had progressed on one previous line of chemotherapy for metastatic disease. Metastatic sites included extensive nodal disease and skin/chest wall lesions. The tumor was negative for PD-L1 expression, was microsatellite stable, and had a low tumor mutational burden (4 mutations/megabase). Positive results from the phase 1 study suggest that additional exploration of treatment with CX-072 monotherapy in the TNBC patient population is warranted.

Dose expansion trial design: The phase 2 dose expansion part of the PROCLAIM-CX-072 study will include enrollment of TNBC patients with skin metastases. Key inclusion criteria for patients in the TNBC cohort are as follows: naive to immunotherapy (PD-1/PD-L1 and CTLA-4 inhibitors), approved immune checkpoint inhibitor agents not available, histologically confirmed triple negative (estrogen receptor–, progesterone receptor–, and human epidermal growth factor receptor-2–negative cancer per ASCO-CAP guidelines), previously treated with 1 to 3 systemic chemotherapy regimens, and locally advanced and recurrent skin or subcutaneous metastases not suitable for surgical resection or radiotherapy. Patients will receive doses of 10 mg/kg CX-072 intravenously every 2 weeks. Efficacy will be evaluated using RECIST v1.1 and immune-related RECIST criteria. Safety and tolerability will be assessed based on the incidence and severity of adverse events (categorized by NCI CTCAE criteria, v4.03) and relationship to study drug. Other analyses will include pharmacokinetics, incidence of anti-drug antibodies against CX-072, exploratory analysis for immune response, and CX-072 activation in the tumor.

PROBODY is a trademark of CytomX Therapeutics, Inc.

Citation Format: Adams S, Hamilton E, Ott PA, Cho D, Kalinsky K, LoRusso P, Will M, Huels V, Benson B, Murias C, Arkenau H-T. PROCLAIM-CX-072: Monotherapy for advanced triple negative breast cancer with skin metastases in a phase 1-2 trial of the PD-L1 probody therapeutic CX-072 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-31.