Researchers today (Monday 22 June) presented results from a phase 1 study, that saw some cancer patients receive vaccines based on unique information taken from their own tumor. Researchers found the personalized treatment was well tolerated, with patients largely experiencing low to moderate side effects.
Dr. Juanita Lopez, a Consultant Medical Oncologist at the Oak Drug Development Unit at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (ICR), explained: “Many cancers are able to successfully avoid the immune system, and we are only starting to understand the myriad ways in which cancers can do this. Because mutations are not shared between cancers, a personalized treatment approach that targets individual tumor neoantigens may be a viable immunotherapeutic strategy for numerous patients with cancer.”
Clinicians led by The Royal Marsden, The Institute of Cancer Research, London, and Barts Health NHS Trust investigated the vaccine, RO7198457, when given in combination with the immunotherapy drug atezolizumab (Tecentriq), in 144 patients who had advanced cancers. Cancer types ranged but included lung, breast, colorectal, and melanoma. Patients had received several treatments previously, with nearly 40 percent having had prior immunotherapy.
To produce the vaccine, samples of the tumor and blood are taken and run through an algorithm. This finds a part of the tumor that the body would recognize as ‘foreign’ and uses the information to create a vaccine that is unique for that patient. When given back to the patient, alongside the immunotherapy, it is hoped the body elicits an immune response, identifying and killing those cancer cells.
During the induction phase of treatment, patients received one of the different doses of RO7198457 ranging from 15 to 50 micrograms once per week for six weeks; the seventh and eighth doses were administered fortnightly. Atezolizumab was given on a 21-day cycle. Patients received a booster dose of the vaccine during the seventh cycle of atezolizumab, along with a maintenance dose of the vaccine every 24 weeks following the induction phase.
Of the 108 patients who had at least one tumor assessment, nine responded, representing an overall response rate of 8 percent. One patient with colorectal cancer had a complete response, and 53 patients, representing 49 percent of evaluable patients, had stable disease.
Researchers found when they analyzed blood samples of 63 patients, the immune system in 73 percent had been activated in response to the vaccine.
The clinical response rate was therefore low overall but did provide researchers with information for future research.
We were able to generate tumor-specific immune responses in the majority of evaluable patients, using a personalized cancer vaccine approach in combination with immune checkpoint blockade.
Dr. Lopez, who presented the results at this year’s virtual AACR conference (American Association for Cancer Research), added: “We were able to generate tumor-specific immune responses in the majority of evaluable patients, using a personalized cancer vaccine approach in combination with immune checkpoint blockade. It is like our overall low clinical response rate is due to the advanced disease many patients had, and the large number of treatments they had already received.”
Researchers are looking to expand this area of investigation, to understand the potential for patients with earlier-stage cancers, and with a larger patient population.
The study was funded by Genentech and BioNTech. Limitations of the study include a small sample size. Furthermore, due to the single-arm nature, the study results cannot be directly compared with atezolizumab monotherapy.
The Oak Foundation Drug Development Unit is a joint unit of The Royal Marsden and The Institute of Cancer Research, London. The unit treats close to 300 patients a year on Phase I trials, making it one of the largest facilities of its kind in the world. The Unit was funded thanks to a donation by The Oak Foundation to The Royal Marsden Cancer Charity, and since opening has continued to have a global impact with novel drug treatments.
Supported by The Royal Marsden Cancer Charity
Supporters of The Royal Marsden Cancer Charity have enabled the Charity to help improve the patient experience for children and their families. The Charity contributed £16 million to the cost of the Oak Centre for Children and Young People when it was built and have since funded the creation of break-out spaces such as the Pandora parents’ lounge and outdoor play areas.
The Charity continues to fund a number of different services within the centre including a team of play specialists who use their understanding of child development, therapeutic play activities, and distraction techniques to help young patients prepare for and cope with painful or invasive procedures, scans, and treatment and to ensure the service runs smoothly. The Charity also supports the pain management team, who work closely with the physiotherapists and psychologists to help children and young people improve their pain management and find ways of coping.