403P - Phase I Studies of the Novel Carcinoembryonic Antigen T-cell Bispecific (CEA-CD3 TCB) Antibody as a Single Agent and in Combination with Atezolizum...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Drug Development
Colon Cancer
Cancer Immunology and Immunotherapy
Rectal Cancer
Presenter Neil Segal
Citation Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
Authors N.H. Segal1, J. Saro2, I. Melero3, W. Ros4, G. Argiles5, A. Marabelle6, M.E. Rodriguez Ruiz3, J. Albanell7, E. Calvo8, V. Moreno9, J.M. Cleary10, J.P. Eder11, V. Karanikas2, S. Bouseida12, F. Sandoval12, D. Sabanes13, S. Sreckovic14, H.I. Hurwitz15, L. Paz-Ares16, J. Tabernero17
  • 1Department Of Medicine, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2Roche Pharmaceutical Research And Early Development, Roche Innovation Centre, Zurich/CH
  • 3Immunology And Immunotherapy Department, CIMA, CUN University of Navarra, 31009 - Pamplona/ES
  • 4Molecular Pathology, Netherlands Cancer Institute, Amesterdam/NL
  • 5Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 6Département D’innovation Thérapeutique Et D’essais Précoces, Gustave Roussy, Université Paris-Saclay, Villejuif/FR
  • 7Medical Oncology Department, Hospital del Mar, Pompeu Fabra University, 8003 - Barcelona/ES
  • 8Medical Oncology, START Madrid, Centro Integral Oncologico Clara Campal, Madrid/ES
  • 9Start Madrid-fjd, Hopital Fundacion Jimenez Diaz, 28040 - Madrid/ES
  • 10Early Drug Development Center, Dana-Farber Cancer Institute, Boston, MA/US
  • 11Early Drug Development Program, Yale University Cancer Center New Haven Hospital, New Haven, CT/US
  • 12Roche Pharmaceutical Research And Early Development, Roche Innovation Centre, Basel/CH
  • 13Biostatistics, F Hoffmann-La Roche Ltd., Basel/CH
  • 14Safety Science, F Hoffmann-La Roche Ltd., Basel/CH
  • 15Duke Cancer Institute, Duke University Medical Center, 27710 - Durham/US
  • 16Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid/ES
  • 17Biomédica En Red De Oncología, Centro de Investigación, 31009 - Madrid/ES

Abstract

Background

CEA-CD3 TCB (RG7802, RO6958688) is a novel T-cell bispecific antibody targeting CEA on tumor cells and CD3 on T cells. Preclinically, CEA-CD3 TCB had potent antitumor activity, leading to increased intratumoral T-cell infiltration and activation, T-cell–mediated tumor cell killing and PD-L1/PD-1 upregulation.

Methods

In 2 ongoing dose-escalation phase I studies, CEA-CD3 TCB is given as monotherapy IV QW (S1) or in combination (QW) with atezolizumab 1200 mg Q3W (S2) in pts with advanced CEA positive (> 20% of tumor cells expressing moderate or high) solid tumors. In S1, 80 pts (70 CRC) were treated at dose levels of 0.05-600 mg; in S2, 45 pts (35 CRC) at 5-160 mg.

Results

At doses ≥ 60 mg (31 evaluable pts with CRC in S1; 14 in S2), CT scans revealed signs of tumor inflammation within 48 h of the first dose, consistent with CEA-CD3 TCB mode of action. 2 (6%) CRC pts in S1 (both microsatellite stable [MSS]) and 3 (21.5%) in S2 (2 MSS CRC, 1 MSI high [out of 2]) had confirmed partial response (PR; RECIST v1.1). Additionally, tumor reduction of − 10% to − 30% (stable disease) was seen in MSS CRC pts (4 [13%] in S1 and 5 [36%] in S2). At weeks 4-6, 9 (29%) CRC pts in S1 and 7 (50%) in S2 had metabolic PR (FDG PET; EORTC criteria). At all doses in S1, the most common related AEs were pyrexia (56%), infusion-related reactions (IRRs; 50%) and diarrhea (40%). In S1 (out of 59 pts > 40 mg), the most common grade ≥ 3 (G3) related AEs were IRRs (24%) and diarrhea (7%). Five pts experienced DLTs: G3 dyspnea, G3 diarrhea, G3 hypoxia, G4 colitis and G5 respiratory failure (G4 and G5 at 600 mg [exceeding MTD]). DLT events were likely associated with tumor lesion inflammation, per investigators. In S2, there was no evidence of new or additive toxicities, with 2 DLTs at 160 mg (1 G3 ALT increase in a pt with liver metastases and 1 G3 maculopapular rash). Updated data will be presented.

Conclusions

Evidence of antitumor activity in advanced CRC and other CEA-expressing tumors was observed during dose escalation with CEA-CD3 TCB monotherapy. Enhanced activity and a manageable safety profile was seen in combination with atezolizumab.

Clinical trial identification

NCT02324257

Legal entity responsible for the study

F Hoffmann-La Roche Ltd.

Funding

F Hoffmann-La Roche Ltd.

Disclosure

N.H. Segal: Advisory board and research funding from Genentech/Roche, MedImmune/AstraZeneca, Bristol-Myers Squibb, Merck and Pfizer. J. Saro: Employee of Roche and stock holder of Roche. I. Melero: Advisory board: Bristol-Myers, Roche-genentech, AstraZeneca, Lilly, Merck Serono, Bayer, Genmab, Alligator, Bioncotech, Tusk Grants from: Roche-Genetech, Bristol-Myers, Bioncotech. A. Marabelle: PI: Roche, Bristol-Myers Squibb, Merck, Pfizer, Lytix, Eisai, Astra Zen Kyowa Kirin Pharma, Novartis, Bristol-Myers Squibb, Symphogen, Genmab, Amgen, Biothera, Nektar, GSK, Oncovir, Seattle Genetics, Flexus Bio, Pierre Fabre, Onxeo, Bayer, Daichii Sankyo, Imaxio, Sanofi, BioNTech. J.M. Cleary: Research funding to his institution from Merrimack Pharmaceuticals, Taiho Oncology, Merck, Roche, Abbvie, Precision Biologics, and Bristol-Myers Squibb. V. Karanikas, S. Bouseida, F. Sandoval, D. Sabanes: Roche employee. S. Sreckovic: Roche employee and in a possession of Roche stock. H.I. Hurwitz: Honoraria: Roche and Lilly Consultant: Roche, Bristol-Myers Squibb, Lilly, Novartis, Incyte, TRACON Pharma, Acceleron Pharma, GlaxoSmithKline, OncoMed Institutional Funding: Roche, GlaxoSmithKline, Novartis, TRACON Pharma, Bristol-Myers Squibb, Regeneron, Lilly, Macrogeneics, NCI. L. Paz-Ares: Scientific Advise to Roche, Bristol-Myers Squibb, MSD, AstraZeneca, Novartis, Lilly, Pfizer and Merck AG. J. Tabernero: Advisory boards for Amgen, Bayer, Boehringer Ingelheim, Celgene, Chugai, Genentech, Lilly, MSD, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Symphogen, Taiho, and Takeda. All other authors have declared no conflicts of interest.