This study will collect information on immune response and adverse events after vaccination against coronavirus disease (COVID-19) in a vulnerable patient cohort. Understanding the ability or disability to mount a protective immune response after vaccination will help to counsel patients during the pandemic and support decisions on whom to vaccinate and to identify patients who require other measures to protect them from COVID-19.

Rationale:

Patients with cancer have an increased risk of adverse outcome of COVID-19, which is determined by their underlying disease and/or cancer treatment. Therefore, vaccination of cancer patients against COVID-19 is recommended. However, phase III studies do not provide robust information on efficacy and safety in this vulnerable population. In patients with cancer, the disease itself, but also immunotherapy and chemotherapy, may have a significant impact on the ability to develop an effective immune response to COVID-19 vaccination, and could even increase the risk of adverse events.

Objective:

To assess immune response and adverse events after administration of one approved vaccine against COVID-19 in patients with cancer treated with immunotherapy and/or chemotherapy.

Study design:

This is a prospective multicenter, multicohort study.

Study population:

Four cohorts will receive vaccination against COVID-19:

A. Individuals without cancer (N=246, i.e., partners of patients in cohort B, C, and D) B. Patients with cancer treated with immunotherapy (N=135) C. Patients with cancer treated with chemotherapy (N=246) D. Patients with cancer treated with chemo-immunotherapy (N=246)

Intervention:

Participants will be vaccinated against COVID-19 with an approved vaccine. Blood will be drawn at different time points by venipuncture and mucosal lining fluid will be collected at 2 time points.

Main study parameters/endpoints:

The primary endpoint is the antibody based immune response on day 28 after the second vaccination. Participants will be classified as responders or non-responders. The definition of response is seroconversion defined as presence of SARS-CoV-2 spike S1-specific IgG antibodies in individuals without measurable anti-S antibodies at baseline. Participants who are seropositive at baseline will not be included in the analysis of the primary endpoint. The percentage of responders of each patient cohort will be compared with the percentage responders in the control group. Safety is a secondary endpoint which will be reported in terms of percentage of solicited local and systemic adverse events (AEs) graded according to severity. Other secondary endpoints include longevity at 6 months and levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific T cell responses.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Participants will have to visit the hospital at 6 time points and participants who receive a third vaccination will have 2 additional hospital visits. The vaccine will be administered two times according to standard of care, with the option of a third vaccination for participants without an adequate response after 2 vaccinations. Blood will be drawn (~373 ml in total for participants receiving 2 vaccinations, and ~539ml in participants receiving 3 vaccinations) prior to the vaccinations and at day 28 and 6 months, 11 months and 18 months after the second vaccination. Nasal mucosal lining fluid samples will be collected at baseline and day 28 after the second vaccination in a subgroup of patients. Blood sampling will give minor discomfort. Vaccination can cause AEs including fatigue, chills, headache, myalgia, and pain at the injection site. For seven days after each vaccination, participants will be asked to record local and systemic reactions using a questionnaire. At baseline and at 3, 6, 9, 12, 15 and 18 months after the second vaccination, patients will be asked to complete questionnaires about potential subsequent testing for SARS-CoV-2, diagnosis of COVID-19, and severity of COVID-19.

This study will collect information on immune response and adverse events after vaccination against COVID-19 in a vulnerable patient cohort. It will also explore immune response and safety of a third vaccination in participants without an adequate antibody response after the second vaccination. Understanding the ability or disability to mount a protective immune response after vaccination will help to counsel patients during the pandemic and support decisions on whom to vaccinate and to identify patients who require other measures to protect them from COVID-19. Participants will be informed about their antibody titer in a letter that includes an explanation about what this means to them. This will be done after antibody measurements have been completed for day 28 after second vaccination, and again after completion of measurements for 6 months and 28 days after third vaccination, and 11 months and 18 months after the second vaccination.

Inclusion Criteria:

To be eligible to participate in this study, a subject must meet all of the following criteria:

• Age of 18 years or older
• Life expectancy > 12 months
• Ability to provide informed consent

Additional criteria for cohort A:

• Partner of a participating patient

Additional criteria for cohort B:

• Histological diagnosis of a solid malignancy
• Treatment with monotherapy immune checkpoint inhibitor (ICI) against Programmed Death 1 (PD1) or its ligand PD-L1 (in curative or non-curative setting)
• Last ICI administration within 3 months of vaccination

Additional criteria for cohort C:

• Histological diagnosis of a solid malignancy
• Treatment with cytotoxic chemotherapy (monotherapy and combination chemotherapy is allowed, as well as a combination with radiotherapy, in curative or non-curative setting)
• Last chemotherapy administration within 4 weeks of vaccination

Additional criteria for cohort D:

• Histological diagnosis of a solid malignancy
• Treatment with a PD1 or PD-L1 antibody in combination with cytotoxic chemotherapy (in curative or non-curative setting)
• Last chemotherapy administration within 4 weeks of vaccination
• Last ICI administration within 3 months of vaccination

Exclusion criteria:

• Confirmed SARS-CoV-2 infection (current or previous)
• Women who are pregnant or breastfeeding
• Active hematologic malignancy
• Any immune deficiency not related to cancer or cancer treatment (e.g. inherited immune deficiency or known infection with Human Immunodeficiency Virus)
• Systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medication within 14 days of vaccination. Inhaled or topical steroids, and adrenal replacement steroids (> 10 mg daily prednisone equivalent) are permitted. In addition, standard of care with short course steroids to prevent nausea and allergic reactions from chemotherapy or iodinated CT contrast is allowed.

Additional criteria for cohort A:

• Current or previous diagnosis of a solid malignancy, unless treated with curative intent >5 years before enrolment and without signs of recurrence during proper follow-up
• Previous history of a hematologic malignancy

Additional criteria for cohort B:

• Treatment with cytotoxic chemotherapy within 4 weeks of vaccination

Additional criteria for cohort C:

• Treatment with an ICI within 3 months of vaccination

Alignment and reuse Our options for reusing data, biological materials, and/or other resources (from research or practice) in your project.

• Data: Clinicopathological parameters as described in the protocol
• Biological materials: Blood
• Research software: R statistical package, Castor, MOLGENIS
• Other resources, i.e.,Nederlandse Kankerregistratie (NKR), the Dutch Cancer Registry, electronic patient dossiers (EPDs)

FAIR data within the COVID-19 research community

• A COVID-19 related or other Findability, Accessibility, Interoperability, and Reuse (FAIR) data points
• COVID-19 research platform for data sharing

we will make protocol etc. available on the website soon voicetrial.nl

we start the make interim results available second half of 2021

we aim to share as much as possible also through own website, and COVID-19 platforms that are considered for this kind of research