Oxford UK, 20 January 2022 – Celleron Therapeutics, the UK-based company developing personalised medicines for cancer patients, announced today a 14.5% patient two-year survival rate following treatment in their Phase II clinical trial testing the immune check point inhibitor (ICI) nivolumab in combination with zabadinostat in patients suffering from advanced micro-satellite stable colorectal cancer (MSS CRC).
Celleron Therapeutics’ Phase II clinical trial (the CAROSELL Study) tested the effect of zabadinostat (formerly CXD101) in combination with nivolumab in MSS CRC, which typically does not respond to immune checkpoint inhibitors agents as mono-therapy. The clinical trial strategy rests on compelling pre-clinical results which provide novel insights into how zabadinostat and ICI drugs work together to re-engage recognition of tumours by the immune system, frequently described as turning ‘cold’ tumours ‘hot’. The patients studied, had advanced or metastatic disease, having relapsed after at least two previous lines of therapy.
Enrolment to the Phase II study was completed in May 2019, and all ongoing subjects have completed the study treatment. Interim analysis of the evaluable MSS CRC subjects saw a significant level of durable disease control (stable disease plus partial response) and overall response rate (ORR). Patients have now been followed-up for survival post-study treatment, where 14.5% of the subjects had survived for two years or more, from first dose of study treatment. This clinical activity compares favourably with products that have been approved to treat MSS CRC, such as Stivarga (regorafenib) and Lonsurf (trifluridine/tipiracil tablets).
Professor David Kerr, Chief Medical Officer and Founder of Celleron Therapeutics, commented:
“We continue to be extremely excited by these encouraging Phase II trial results which add to the continuing evidence that zabadinostat is a clinically viable drug with wide utility in metastatic colorectal cancer. We expect to further develop our understanding of these responses with our upcoming precision-medicine Phase III study”.
About Colorectal Cancer
Colorectal cancer is the second most common tumour type in women, and the third most common in men, globally. The approximate five-year survival rate for colorectal cancer patients in the United States is 10% for those with advanced metastatic disease (Stage IV).
Surgery is indicated for localized disease, whilst chemotherapy has been the standard management for patients with metastatic colorectal cancer. Two agents have been approved for third line management of advanced colorectal cancer, namely regorafenib (Stivarga) and Trifluridine-tipiracil hydrochloride (Lonsurf).
A subset (5%) of colorectal cancers is characterized with deficient DNA mismatch repair (dMMR or microsatellite instability, MSI). These tumours tend to have a high expression of checkpoint proteins (PD-1 and PD-L1), which interfere with the body’s normal anti-tumour T-cell response. By disabling these proteins, immune checkpoint inhibitors (ICI) such as nivolumab allow the immune system to function properly, and T-cells to kill tumour cells.
However, the majority of patients with a normal Mismatch Repair proficient expression, the microsatellite phenotype is stable (MSS), antigen presentation is believed to be much decreased, and the tumour is thus resistant to checkpoint inhibition. Most MSS patients will ultimately relapse or become resistant to chemotherapy. There remains a very significant unmet clinical need to find novel agents, singly or in combination, for the treatment of these late-stage patients.
About Celleron Therapeutics Ltd
Celleron Therapeutics is a biopharma advancing a clinical and pre-clinical pipeline of precision therapies for different cancer indications. The company is located on the Oxford Science Park, UK. Celleron Therapeutics has built a proprietary platform around epigenetic control and immune modulation, providing its drugs with a two-pronged attack on cancer.
Celleron Therapeutics’ approach seeks to align the right drug with the right patient enabling a personalised approach to cancer therapy.
Celleron Therapeutics’ focus is on those cancers where there is still an unmet need for long-term disease control. It is hoped that not only will patients volunteering for our clinical trials benefit directly, but the results from these studies will ultimately allow the general use of more effective, safer medicines. Our goal is not only to treat cancer but improve quality of life during therapy by reduction of side effects.
Celleron has global license partnerships with Astra Zeneca and Roche. The company secured investment in 2016 from a consortium of South Korean investors; and in 2020 span out an affiliate company, SynOx Therapeutics. For more information see www.cellerontherapeutics.com
Zabadinostat (formerly CXD101) is Celleron Therapeutics’ next generation epigenetic immune-regulator representing a class of drug that kills cancer cells by blocking certain vital functions involved in gene expression (histone–deacetylase [HDAC] inhibitor) and reactivates the patient’s immune system so that cancer cells can no longer evade immune recognition.
The European Medicines Agency (EMA) has previously granted zabadinostat Orphan Drug Designation as single agent therapy, based upon early-phase trial efficacy seen in relapsed or refractory Peripheral T-Cell Lymphoma (PTCL) patients. A PTCL Phase II trial is scheduled to start 2022 in China.