1. What are the current main characteristics of clinical trials for cancer treatments?
Sarah Bischof: Oncology is a leading area for innovative R&D on many metrics – whether number of active approaches, the level of targets being pursued, or clinical trial activity. It is common for novel drugs to focus on metastatic or advanced cancers first, but trials for early cancers have more than doubled in 10 years. Almost 6,000 ongoing clinical trials are currently investigating therapeutic approaches targeting PD-1/-L1 inhibitors, while hundreds and thousands of studies are investigating treatments based on novel immune-oncological assets in hematological and solid tumors. This puts huge pressure on patient recruitment.
Companies may have clinical-stage pipelines running from one to multiple drugs, targeting rare and ultra-rare cancers through to more common tumor indications where an unmet medical need still exists. invIOs is currently running a phase 1b trial of its lead candidate cell-therapy treatment APN401. Because the trial is designed as a basket study, we can enroll patients with various solid tumors. Patients who have already undergone two or more lines of therapy are eligible as there is no other effective treatment available to them.
In a Phase 1 clinical trial in oncology, we are able to judge whether an experimental treatment is safe and well tolerated, and what is the best dosage. In the case of cutting-edge cell therapies such as APN401, the definition of a maximum tolerated dose (MTD) may be replaced by a maximum manufacturable dose. This trial phase may also include secondary endpoints such as surrogate parameters for anti-tumor immune response, which can be measured by release of cytokines and chemokines aimed at killing tumor cells.
From the patient point of view, participation in a clinical trial opens up access to new treatments before they become widely available after successful clinical development and registration. In many tumor indications, where huge unmet medical need still exists despite years of progress in research, access to novel therapies via clinical trials is therefore a motivation for patients and their families to become partners in the scientific discovery process.
2. What impact did COVID-19 have on clinical cancer trials?
Sarah Bischof: Cancer diagnoses decreased in 2020 and 2021 during the height of the global pandemic, mainly because people avoided going to doctors and hospitals. However, the disease did not go away, so with more patients going undiagnosed and untreated, we may see the impact of COVID-19 disruptions on cancer and the healthcare system in the longer term. Cancer treatment continued to be delivered during the pandemic, although a backlog in screenings raised worrying questions.
For us, a clinical-stage small biotech company, COVID-19 brought some challenges, but we are confident that we have now returned to routine clinical development. We are making progress with our approaches in a clinical setting and have built up valuable collaborations and networks with academia and clinicians. We are excited about the future and are making plans to advance other novel assets from our EPiC cell therapy platform into clinical studies in the near future, in addition to APN401, as well as a novel small molecule.
3. From a clinical perspective, what is special about invIOs’ cell therapy platform EPiC targeting the novel immune checkpoint Cbl-b?
Sarah Bischof: We want our approaches to become successful examples of personalized cancer cell therapies for treating solid tumors. Our approach is based on white blood cells (PBMCs) which are activated by silencing the master checkpoint inhibitor Cbl-b. In terms of clinical development, it is fascinating to see how individual our patients are in terms of the composition of their immune cells, and how well the APN401 therapy is tolerated in patients with advanced solid tumors.
Adoptive cell therapies have huge potential to bring about positive change for cancer patients compared to existing treatments such as CAR-T cell therapies. These have become an important cornerstone of modern oncology but are still limited to treating hematological indications. CAR-T treatments may have severe side effects, while CAR-T cell manufacturing is a laborious and complex centralized process taking up to several weeks. Moreover, these treatments can have severe side effects, as permanent transgene expression is required to achieve durable clinical responses to commercial CAR-T therapies.
With APN401, by contrast, siRNA technology is applied transiently and specifically to silence Cbl-b, thus removing the brake on anti-tumor immune responses. Our approach is also tailored to the patient, with short needle-to-needle times of approximately 24 hours. Because we use our patients’ most recent immune cell repertoire for each treatment cycle and processing takes place on-site, we avoid the need for long shipment times and complex handling procedures such as cryopreservation. While our initial promising results to date will certainly need validation in larger clinical trials, the process so far resembles an almost “off-the-shelf” but still autologous solution.
About Sarah Bischof, Head of Clinical Operations at invIOs, Vienna
- Over 13 years of experience of conducting and managing clinical trials
- Previously lead Clinical Affairs (Monitoring and Regulatory) at the Phase I unit at Medical University of Graz
- Clinical Research Associate for national and international CROs
- Project manager and Safety Associate for the pharmaceutical industry