2017 ASCO Annual Meeting!
Session: Developmental Therapeutics—Immunotherapy
Type: Oral Abstract Session
Time: Monday June 5, 1:15 PM to 4:15 PM
Location: Hall D1
Phase Ia and Ib studies of the novel carcinoembryonic antigen (CEA) T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab: Preliminary efficacy and safety in patients with metastatic colorectal cancer (mCRC).
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 3002)
Author(s): Josep Tabernero, Ignacio Melero, Willeke Ros, Guillem Argiles, Aurelien Marabelle, Maria E. Rodriguez-Ruiz, Joan Albanell, Emiliano Calvo, Victor Moreno, James M. Cleary, Joseph Paul Eder, Vaios Karanikas, Said Bouseida, Federico Sandoval, Daniel Sabanes, Sasha Sreckovic, Herbert Hurwitz, Luis G. Paz-Ares, Jose M. Saro Suarez, Neil Howard Segal; Vall d’Hebron University Hospital Institute of Oncology (VHIO), Barcelona, Spain; CIMA, CUN, University Navarra, Centro de Investigación Biomédica en Red de Oncología (CIBERONC), Pamplona, Spain; Netherlands Cancer Institute, Amsterdam, Netherlands; Gustave Roussy, Université Paris-Saclay, Villejuif, France; CIMA, CUN, University Navarra, Centro de Investigación Biomédica en Red de Oncología (CIBERONC), Madrid, Spain; Medical Oncology Department, Hospital del Mar, Barcelona, Spain; START Madrid, Centro Integral Oncológico Clara Campal, Madrid, Spain; START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain; Dana-Farber Cancer Institute, Boston, MA; Yale Cancer Center, New Haven, CT; Roche Innovation Center, Zurich, Switzerland; Roche Innovation Center, Basel, Switzerland; F. Hoffmann-La Roche Ltd., Basel, Switzerland; Duke University Medical Center, Durham, NC; Medical Oncology Department, Hospital 12 de Octubre, Madrid, Spain; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Background: CEA CD3 TCB (RG7802, RO6958688) is a novel T-cell bispecific antibody targeting CEA on tumor cells and CD3 on T cells. In preclinical models, CEA CD3 TCB displays potent anti-tumor activity, leads to increased intra-tumoral T cell infiltration and activation and upregulates PD-1/PD-L1. Methods: Intwo ongoing dose-escalation phase I studies, RO6958688 is given as monotherapy (S1) i.v. QW or in combination (QW) with atezolizumab 1200 mg Q3W (S2) in adult patients (pts) with advanced CEA+ solid tumors. In S1, 80 pts (mCRC: 68) were treated at dose levels from 0.05 mg to 600 mg; in S2, 38 pts (mCRC: 28) from 5 mg to 160 mg. In S1, a Bayesian logistic regression model with overdose control guided dose escalation. Data cutoff 25.01.17. Results: At doses ≥60mg (36 pts in S1; 10 in S2), CT scans revealed tumor inflammation within days of first dose, consistent with the mode of action of RO6958688. 2 (5%) pts in S1 (both microsatellite stable (MSS) and 2 (20%; 1 MSS) in S2 had a partial response (RECIST v1.1). Preliminary tumor size reduction ( > -10% and < -30% [stable disease]) was observed in 4 (11%) additional pts in S1 and 5 (50%) in S2. At week 4-6 FDG PET scan assessment, 10 (28%) pts with mCRC in S1 and 6 (60%) in S2 had a metabolic partial response (EORTC criteria). At all doses in S1, the most common related AEs were pyrexia (56.3%), infusion related reaction (IRR, 50%) and diarrhea (40%). The most common grade ≥ 3 (G3) related AEs were IRR (16.3%) and diarrhea (5%). 5 patients experienced DLTs: G3 dyspnea, G3 diarrhea, G3 hypoxia, G4 colitis and G5 respiratory failure (G4-5 at 600mg). DLT events were likely associated with tumor lesion inflammation. In S2, there was no evidence of new or additive toxicities, with 1 DLT at 160 mg (G3 transient increase of ALT in a patient with liver metastases). PK/PD data are reported separately. Conclusions: Evidence of antitumor activity was observed with RO6958688 monotherapy in ongoing dose escalation. Activity appeared to be enhanced with doses in combination with atezolizumab, with a manageable safety profile. Updated data will be presented. Clinical trial information: NCT02324257 and NCT02650713