Roche presents the first Phase I efficacy and safety data on CEA-TCB (CEA CD3 TCB), a novel T-cell bispecific antibody targeting solid tumours

Basel, 18 May 2017

Roche presents the first Phase I efficacy and safety data on CEA-TCB (CEA CD3 TCB), a novel T-cell bispecific antibody targeting solid tumours

  • Encouraging clinical activity in metastatic colorectal cancer after failure of at least two prior chemotherapy regimens to be presented at the ASCO Annual Meeting

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from two Phase I studies evaluating the novel cancer immunotherapy CEA-TCB (RO6958688; RG7802), a molecule that binds T-cells and tumour cells simultaneously. CEA-TCB was studied in patients with carcinoembryonic antigen (CEA)-positive solid tumours, including microsatellite stable (MSS) metastatic colorectal cancers (mCRC) that overexpress CEA and progressed after at least two prior chemotherapy regimens.1 The studies demonstrated encouraging anti-tumour activity of CEA-TCB as a monotherapy, which was further enhanced in combination with TECENTRIQ® (atezolizumab). 

In the monotherapy, out of 31 patients with mCRC treated with CEA-TCB doses of 60mg or above, 14 patients (45%) showed either partial response (n=2, 6%) or stable disease (n=12, 39%). For the combination, of 25 patients treated with doses of 5–160mg of CEA-TCB, 11 patients with MSS mCRC were treated at doses shown to induce tumour lesion inflammation (80 and 160 mg). Nine of these patients (82%) showed either a partial response (n=2, 18%) or stable disease (n=7, 64%) in this difficult-to-treat population.

CEA-TCB showed favourable pharmacokinetics and a manageable safety profile in both monotherapy and combination therapy with TECENTRIQ. Including all adverse events (AEs) in both studies, the majority of AEs were Grade 1–2, with 7.9% being Grade 3 or higher in the monotherapy trial and 8.1% being Grade 3 or higher in the combination trial. Two treatment-related AEs with severity greater than grade 3, (one Grade 4, one Grade 5), occurred in the monotherapy dose escalation at the highest dose level, which exceeded the maximum tolerated dose (MTD) in cycle 1. The results of these Phase I studies will be presented at the 2017 American Society for Clinical Oncology (ASCO) Annual Meeting which takes place from 2–6 June in Chicago, IL, United States.1

“These early data in heavily pre-treated metastatic colorectal cancer are particularly encouraging because there is a critical need to improve outcomes for people living with this disease,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “CEA-TCB is currently being further investigated in Phase I clinical trials and has the potential to be combined with a wide variety of other agents. We look forward to continuing the development of this novel cancer immunotherapy across a range of CEA-positive cancers.”

CEA-TCB uses a novel 2-to-1 molecular design. It is engineered to bind simultaneously with one arm to CD3 on T-cells and with two arms to CEA on tumour cells, bringing T-cells into close proximity to the cancer cells. This leads to T-cell activation and subsequent tumour cell killing.

A summary of the Phase I results to be presented at ASCO are provided below.

  • Study 1: 80 patients (MSS mCRC: 70) treated; 31 available for efficacy evaluation at data cut-off 
  • Study 2: 45 patients (MSS mCRC: 35) treated; 25 available for efficacy evaluation at data cut-off 

Efficacy and safety results

About metastatic colorectal cancer

Colorectal cancer (CRC) is the third most common cancer in men (746,000 cases, 10.0% of the total) and the second in women (614,000 cases, 9.2% of the total) worldwide.2 Almost 55% of the cases occur in more developed regions. Incidence rates vary 10-fold in both sexes worldwide.2 The global burden of CRC is expected to increase by 60% to more than 2.2 million new cases and 1.1 million deaths by 2030.3

About CEA-TCB

CEA-TCB is a novel T-cell bispecific antibody being investigated for the treatment of carcinoembryonic antigen (CEA)-expressing solid tumours. As CEA is overexpressed in a variety of cancers, including colorectal cancer (CRC), CEA-TCB has the potential to work in a broad range of solid tumours. CEA-TCB uses a novel 2-to-1 molecular design. It is engineered to bind simultaneously with one arm to CD3 on T-cells and with two arms to CEA on tumour cells, bringing T-cells into close proximity to the cancer cells. This leads to T-cell activation and subsequent tumour cell killing.

About Roche in cancer immunotherapy

For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

About personalised cancer immunotherapy

The aim of personalised cancer immunotherapy (PCI) is to provide patients and physicians with treatment options tailored to the specific immune biology associated with a person’s individual tumour. The purpose is to inform treatment strategies that provide the greatest number of people with a chance for transformative benefit. PCI encompasses the search for reliable biomarkers that correlates with clinical benefit either as a monotherapy or in combination, and across a broad range of tumour types. The Roche PCI research and development programme comprises more than 20 investigational candidates, 11 of which are in clinical trials.

PCI is an essential component of how Roche delivers on the broader commitment to personalised healthcare. To learn more about the Roche approach to cancer immunotherapy please follow this link:

http://www.roche.com/research_and_development/what_we_are_working_on/oncology/cancer-immunotherapy.htm 

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. 

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Twenty-nine medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry eight years in a row by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2016 employed more than 94,000 people worldwide. In 2016, Roche invested CHF 9.9 billion in R&D and posted sales of CHF 50.6 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.