Cancer Research UK announces first patient dosed in trial for hard-to-treat cancers

Published date:
December 6 2021

Cancer Research UK and Hummingbird Bioscience today announce the first patient dosed in their first-in-human trial of Hummingbird’s anti-HER3 antibody HMBD-001* for the treatment of people with a range of HER3** driven cancers.

Cancer Research UK is the world’s leading cancer charity, and Hummingbird Bioscience is an innovative clinical-stage biotech company developing precision therapies against hard-to-drug targets in cancer and autoimmune disease.   

Under the terms of the clinical development partnership, Cancer Research UK is sponsoring and managing the phase I/IIa clinical trial through its Centre for Drug Development.   

The trial is exploring the safety and preliminary evidence of activity of HMBD-001 in patients with advanced HER3 positive solid tumours***, both as a monotherapy and in combination with other anticancer drugs. 

Previous attempts to inhibit HER3 have been unsuccessful because they haven’t been able to completely block all the ways in which HER3 is activated. This means that the patient’s cancer can become resistant to the drug. 

HMBD-001 is unique in that it is designed to block all forms of HER3 signalling, which may overcome the issue of drug resistance seen in previous HER3 inhibitors.  

If successful in clinical trials, HMBD-001 could be the first targeted treatment for hard-to-treat HER3 driven tumours. 

People with an extremely rare subtype of cancer involving the receptor known as a neuregulin 1 (NRG1) fusion subtype**** will also be recruited. Patients with this subtype have few available treatment options.  

The trial is being led by chief investigator Professor Johann De Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, where the first trial site opened to recruitment. Additional sites in Oxford and Newcastle will open shortly. 

Researchers at The Institute of Cancer Research are also leading key experiments and statistical analysis for the trial. 

Cancer Research UK and Hummingbird Bioscience expect to see some initial results from the phase I dose escalation phase of the trial in the second half of 2022.  

Dr Nigel Blackburn, Director of Cancer Research UK’s Centre for Drug Development, said:   

“We are thrilled to be working with Hummingbird Bioscience to advance their novel drug candidate into clinical trials.   

“Although HER3 was discovered over 30 years ago, no therapies able to block its cancer-promoting action have been approved. 

“Hummingbird has taken fresh aim at a difficult drug target and has come up with a novel, potentially transformative antibody for cancer patients who desperately need new treatments.” 

Professor Johann De Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:  

“We are delighted to be launching a clinical trial using HMBD-001 to target HER3 driven cancers. Studies indicate that HER3 plays a vital role in the development of drug resistance and the overall fuelling of many types of cancer.  

“We hope HMBD-001 will prove to be effective and that long-term, this trial will help us to further improve outcomes for advanced prostate cancer through this HER3 targeting strategy.” 

Dr Jerome Boyd-Kirkup, Chief Scientific Officer for Hummingbird Bioscience, said:  

“Dosing of the first patient in the clinical trial of HMBD-001, Hummingbird’s most advanced program, marks the beginning of a potentially transformative approach to treating HER3-driven cancers. 

“I am immensely proud of the teamwork that has brought our differentiated program to this point. Hummingbird Bioscience is dedicated to discovering and developing important medicines for cancer and autoimmune disease with our unique Rational Antibody Discovery platform.” 

Notes to editors

For media enquiries please contact Sophie Lane in the Cancer Research UK press office on 020 3469 5661 or, out of hours, 020 3469 8301.

Following the completion of the trial, Hummingbird Bioscience will retain the rights to further advance the HMBD-001 programme and will have the option to acquire the rights to the clinical trial results to support further development of the antibody.  

*HMBD-001 is the first of Hummingbird Bioscience’s deep pipeline of antibody drug candidates to enter clinical trials. Rationally developed using Hummingbird Bioscience’s proprietary Rational Antibody Discovery (RAD) platform, HMBD-001 is the only reported anti-HER3 antibody in clinical development that uses a highly differentiated mechanism of action designed to block the formation of all active HER3 dimers, regardless of NRG1 ligand binding or HER2/EGFR overexpression.  

Previous attempts to block the HER3 receptor have focused on preventing the binding of NRG1 to HER3. But HER2/EGFR levels can be high in cancer cells so the presence of NRG1 is not needed and blocking this protein does not stop the activation of the MAPK/PI3K cancer pathway.   

HMBD-001 uses a different tactic and rather than stopping the binding of NRG1, it directly blocks the point where HER3 and HER2/EGFR bind to one another.  

 This means that even if there are elevated levels of HER2/EGFR, HMBD-001 should prevent the MAPK/PI3K pathway being activated.  

**The Human Epidermal Growth Factor Receptor (HER) family is part of the receptor tyrosine kinome and consists of four members: EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4. The HER3 receptor plays a vital role in activating the MAPK/PI3K signalling pathway which under normal circumstances promotes the growth of healthy cells. In the context of cancer however, over-activation of this pathway causes rapid and uncontrolled cell division, promoting tumour growth.  

***Colorectal carcinoma, head and neck squamous cell carcinoma, melanoma, breast, gastric, ovarian, prostate, and bladder cancers.  

****A subpopulation of cancer patients has been identified with NRG1 fusions in their tumours; that is, the hybridization of the NRG1 gene with another gene to produce NRG1 fusion proteins that potently activate HER3. Professor de Bono’s team have recently demonstrated in patient-derived tumour models, including organoid cultures, the importance of HER3 in advanced prostate cancer, where white blood cells provide the receptor’s activating ligand neuregulin 1 (NRG1) to drive tumour growth.   

About Cancer Research UK’s Centre for Drug Development  

Cancer Research UK has an impressive record of developing novel treatments for cancer. The Cancer Research UK Centre for Drug Development has been pioneering the development of new cancer treatments for 25 years, taking over 140 potential new anti-cancer agents into clinical trials in patients. It currently has a portfolio of 21 new anti-cancer agents in preclinical development, Phase I or early Phase II clinical trials. Six of these new agents have made it to market including temozolomide for brain cancer, abiraterone for prostate cancer and rucaparib for ovarian cancer. Two other drugs are in late development Phase III trials.  

About Cancer Research UK

  • Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research.
  • Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
  • Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years.
  • Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK’s ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 years.
  • Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
  • Together with its partners and supporters, Cancer Research UK's vision is to bring forward the day when all cancers are cured.

For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1022 or visit www.cancerresearchuk.org. Follow us on Twitter and Facebook.

About Hummingbird Bioscience 

Hummingbird Bioscience is a clinical-stage biotechnology company with a proprietary Rational Antibody Discovery (RAD) platform, developing a broad pipeline of novel, precision therapeutics for the treatment of cancer and autoimmune disease.  

We are focused on targets with significant biological validation and disease association that have not been drugged, or are inadequately drugged to date, which we refer to as “hard targets”. Our RAD platform uses data-driven computational and systems biology with the goal of selecting promising protein targets that are associated with dysregulated biology and clinical disease, enabling us to develop antibodies that bind to specific epitopes and have the potential to be advantageous against these targets. We believe our platform has the potential to unlock novel mechanisms of action, making previously undruggable protein targets druggable, offering a significant potential opportunity to benefit patients.  

For more information, please visit www.hummingbirdbioscience.com, and follow Hummingbird Bioscience on LinkedIn and Twitter.  

Media contacts: 
[email protected] 

Stephanie Tan 
APCO Worldwide 
Email: [email protected]