| | | | | The world is experiencing a major health care crisis. Thus far, over 2.5 million infections with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been confirmed in this global pandemic. With health care systems worldwide operating under heavy strain, continuity in care for cancer patients and clinical trials requires adapting treatment and trial procedures to coronavirus disease (COVID-19). |
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Cancer Care in Times of COVID-19
The highly infectious nature of SARS-CoV-2 entails a risk of contagion for anyone entering public areas such as clinics and hospitals. In addition, the immune function of patients with cancer may be reduced by cancer therapy or the disease itself. It is still unclear if patients with cancer run particular risks, but early studies find that they have higher risks of infection1 and severe events2,3, and active cancer is prevalent among patients succumbing to COVID-19 in Italy4. Patients with cancer now have to balance their necessity for medical care against the risk of exposure to SARS-CoV-2 involved in visiting a hospital. To reduce the number of hospital visits, updates in the process of cancer care were implemented, including the postponement of treatment, use of alternative treatments, remote consultations, or attending visits unaccompanied. Patients may be called the day before a scheduled visit to prescreen for signs of infection such as fever, and may be evaluated and treated in dedicated COVID-19 facilities or an outpatient setting. Lastly, several international organizations, such as the European Society for Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO), have provided advice for cancer patients.
Risk/Benefit
Health care practitioners are faced with the task of providing optimal cancer care to patients while minimizing the risk of infection. To this end, frameworks of reprioritization need to be developed. In a recent publication in Nature Reviews, Hanna et al.5 describe a reprioritization scheme based on important clinical and circumstantial factors, including the magnitude of treatment benefit, possible effect of therapy on outcome of viral infection, and the local pandemic status and health care capacity. The authors suggest that in health care systems moderately affected by COVID-19, treatment can be continued for indications where delay of therapy is expected to negatively affect outcome, whereas in scenarios of severe disease outbreak, treatment may only be possible for patients at immediate risk of severe morbidity or death. In any case, prioritization requires weighing of the risk of potential infection against the risk of cancer progression. According to the ESMO, specific risk categories include patients who receive chemotherapy, radiotherapy, bone marrow or stem cell transplantation, or immunosuppressive therapy, and patients with certain blood cancers such as chronic leukemia. Guidance on clinical decision making is provided by different institutions (ESMO, ASCO) and options include delaying therapy, switching to outpatient treatment (e.g., replacing intravenous drugs with oral drugs), and switching to shorter treatment regimens (e.g., with shorter high-intensity radiotherapy regimens). In a discussion of reprioritization treatment of lung cancer in ESMO Open, the authors suggest that adjuvant treatment with limited survival benefit may not be favorable to absolute risk under current circumstances6. On the other hand, neoadjuvant treatment may be an attractive option to delay surgery. In practice, during the COVID-19 pandemic, health care practitioners are urged to apply their medical judgement to take complex decisions on a case-by-case basis.
New Opportunities for Old Drugs
To aid in this global crisis, pharmaceutical companies all over the world are racing to develop vaccines and medication targeting COVID-19. Several companies have found opportunities to repurpose anticancer drugs to treat patients with COVID-19. For example, CYNK-001 (Celularity), an NK-based therapy being developed for multiple indications, will be tested in a Phase I/II trial for the ability to eliminate infected cells7. Patients with COVID-19 may also suffer from the effects of an exaggerated immune response called a ‘cytokine storm’. To address this issue, Jakavi® (Novartis and Incyte), a Janus kinase (JAK) inhibitor used in the treatment of myelofibrosis, will be tested in a Phase III clinical trial8. Early studies have already shown promising early results. For instance, leronlimab (CytoDyn), a C-C chemokine receptor 5 (CCR5) antagonist in development for treatment of triple-negative breast cancer, showed normalization of cytokine levels and CD4/CD8 ratio in eight severely ill patients with COVID-199. The drug has received a Fast Track designation from the Food and Drug Administration (FDA), and a new Phase IIb/III trial has been initiated10.
Challenging Times
While the search for COVID-19 treatments is currently ongoing, oncology trials are encountering hurdles. Many processes of clinical trials are affected, including production and distribution of drugs, administration of treatment, protocol-specified trial assessments, and clinical site monitoring. As of 22Apr2020, GlobalData reports 225 disrupted oncology trials, with disruptions including delay of initiation, suspension of enrollment, and delays in data read-out due to inaccessibility of trial sites for quality control. For example, a Phase II clinical trial assessing ficlatuzumab (AVEO Oncology) in patients with relapsed/refractory acute myeloid leukemia was discontinued by the Sponsor due to a shift in medical priority of the trial sites towards COVID-19 treatment11. A large proportion of trials, such as Phase I trials assessing ATOR-1015 and ATOR-1017 (both Alligator Bioscience) in patients with metastatic cancers, has suspended recruitment of subjects12. Additionally, international trials, such as the Phase IIb BRaVac (RhoVAC) trial for prostate cancer, are expected to be delayed13. The European Medicines Agency (EMA) and the FDA have released emergency guidance documents concerning the conduct of clinical trials, which we have discussed previously in our newsletter. The guidelines recommend that Sponsors should perform dedicated risk assessments and modify the trial conduct accordingly, and consider alternative safety assessments and remote monitoring approaches. Sponsors are encouraged to engage with regulatory authorities as soon as possible upon identifying emergent protocol changes/possible deviations as a result of COVID-19.
Here to Help
We are aware that Sponsors face challenges in preparing for new clinical trials or meeting requirements for ongoing trials. CATO SMS offers support to Sponsors who need to adjust their clinical trials as a consequence of the COVID-19 pandemic. In our webinar “Maintaining Momentum”, a panel of CATO SMS experts will review the key issues contained in the emerging Agency Guidance and offer thoughts on what changes and options for Sponsors may be seen in the coming months. Importantly, new technologies can offer support in facing challenges associated with the conduct of clinical trials in times of social distancing. THREAD offers a decentralized research platform that allows virtual visits and additional solutions for decentralized monitoring of ongoing trials. The THREAD LaunchKit will help deploy the platform to support our Sponsor’s clinical activities. For more information, please see the THREAD website.
Contact our Business Development teams in Europe or North America now to see how we can collaborate.
1 Yu et al. (2020), SARS-CoV-2 transmission in cancer patients of a tertiary hospital in Wuhan, doi:10.1001/jamaoncol.2020.0980
2 Liang et al. (2020), Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China, doi: 10.1016/S1470-2045(20)30096-6
3 Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19), https://www.who.int/publications-detail/report-of-the-who-china-joint-mission-on-coronavirus-disease-2019-(covid-19)
4 Onder et al. (2020), Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy, doi: 10.1001/jama.2020.4683
5 Hanna et al. (2020), Cancer, COVID-19 and the precautionary principle: prioritizing treatment during a global pandemic, doi: 10.1038/s41571-020-0362-6
6 Banna et al. (2020), How we treat patients with lung cancer during the SARS-CoV-2 pandemic: primum non nocere, doi: 10.1136/esmoopen-2020-000765
7 https://www.prnewswire.com/news-releases/celularity-announces-fda-clearance-of-ind-application-for-cynk-001-in-coronavirus-first-in-cellular-therapy-301034141.html
8 https://www.novartis.com/news/media-releases/novartis-announces-plan-initiate-clinical-study-jakavi-severe-covid-19-patients-and-establish-international-compassionate-use-program
9 https://www.cytodyn.com/newsroom/press-releases/detail/405/treatment-with-cytodyns-leronlimab-indicates-significant
10 https://www.targetedonc.com/view/first-patient-treated-in-phase-iibiii-trial-of-leronlimab-for-covid19
11 https://investor.aveooncology.com/news-releases/news-release-details/aveo-oncology-and-biodesix-discontinue-cyfi-2-study-ficlatuzumab
12 https://www.biospace.com/article/releases/alligator-bioscience-informs-about-temporary-halt-of-recruitment-of-new-patients-due-to-the-covid-19-pandemic/
13 https://www.rhovac.com/cision/130C659761C95423/
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| CATO SMS is a full-service clinical and regulatory contract research organization (CRO), specializing in complex areas such as (immuno-) oncology, advanced therapeutics and orphan diseases. We offer regulatory consulting and drug development affairs in addition to clinical trial management services, leveraging the experience and expertise in all disciplines to the full benefit of your company. We are committed to supporting small and mid-sized biotech, top-tier pharmaceutical companies and investigator groups from strategy to approval, from phase I to IV. CATO SMS employs over 320 dedicated professionals with offices and operations in over 25 countries around the globe including the United States (US), Canada, Europe, Israel and South Africa. Offices are strategically located close to the European Medicines Agency (EMA) in Amsterdam, the Netherlands, and the Food and Drug Administration (FDA) in Washington, US. |
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