Inhaled or topical steroids, and adrenal replacement steroid s (> 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. Version number: 6.0, 27 December 2021 22 of 49 Addition al criteria for cohort A:  Current or previous diagnosis of a solid malignancy , unless treated with curative intent >5 years befo re enrolment and with out signs of recurrence during proper follow -up  Previous history of a hematologic malignancy Addition al criteria for cohort B:  Treatment with cytotoxic chemotherapy within 4 weeks of vaccination Addition al criteria for cohort C:  Treatment with an ICI within 3 months of vaccination 4.4 Sample size calculation The primary endpoint is the antibody based immune response on day 28 after the second vaccination in patients receiving cancer treatment as compared to individuals without cancer . Participants are classifie d as responders or non -responders to vaccination against COVID -19. In patients treated with immunotherapy, we assume that the immune response rate is similar to that in individuals without cancer . In patients treated with chemotherapy or chemo -immunotherapy, we expect a lower immune response rate. As the percentage of responders is still unknown for vaccination against COVID -19, especially when a lower rate of immune response is expected, a power calculation for different s cenarios has been performed, thereby comparing cohorts B, C, and D separately with cohort A. Patients receiving immunotherapy (cohort B) vs. individuals without cancer (cohort A) We assume that 90% of the individuals without cancer will be responders an d that this will be similar in patients receiving immunotherapy. If there is truly no difference (90% responders in both groups), then 112 individuals without cancer and 112 patients are required to be 80% sure that the upper limit of a one -sided 95% confi dence interval will exclude a difference in favor of the individuals without cancer of more than 10%. Patients receiving chemotherapy (cohort C) or chemo -immunotherapy (cohort D) vs. individuals without cancer (cohort A) For patient s receiving chemotherapy or chemo -immunotherapy, we expect a lower percentage of responders compared to the group without cancer based on influenza vaccination trials [29]. However, the percentage of responders is still unknown for vaccination against COVI D-19. Therefore, we performed a power calculation for two different scenarios, 1) anticipated true response rate in the groups receiving Version number: 6.0, 27 December 2021 23 of 49 chemotherapy and chemo -immunotherapy of 60% and 2) anticipated true response rate in the groups receiving chemotherapy and chemo -immunotherapy of 40%. Scenario 1: If there is a true difference in favor of the group without cancer of 30% (90% vs. 60%), then 205 individuals without cancer and 205 patients in cohort C and D are required to be 80% sure that the upper limit of a one -sided 95% confidence interval will exclude a difference in favor of the group without cancer of more than 40%. Scenario 2: If there is a true difference in favor of the group without cancer of 50% (90% vs. 40%), then 205 individuals without cancer and 205 patients in cohort C and D are required to be 80% sure that the upper limit of a one -sided 95% confidence interval will exclude a difference in favor of the group without cancer of more than 50%. In summary, these power calculations indicate that f or the cohort C vs. cohort A comparison and for the cohort D vs. A comparison we need a total of 205 individuals without cancer , 205 patients treated with chemotherapy and 2 05 patients treated with chemo -immunotherapy. With these numbers we have enough po wer to assess non - inferiority in both scenarios with a n alpha of 0. 05 and 80% power. Correction for drop -out We expect that a proportion of the participant s will already have SARS -CoV-2 antibodies at baseline and will not be evaluable for the primary endpoint. In addition, we anticipate that there will be a drop -out of participants at later time points. Reasons for drop -out may include death or poor performance status as a result of progr essive malignancy and/or cancer treatment related AEs. Therefore, we will correct for non -evaluable patients by increasing each cohort with 20%. This means that 246 participants will be recruited in cohorts A, C and D, and 135 participants will be enrolled in cohort B. In total, 873 participants ( 627 patients and 246 individuals without cancer ) will be included. 5. TREATMENT OF SUBJECTS Vaccination will be performed according to the standard of care. The name of the vaccine, batch number and date and time of administration will be recorded. This study investigates the immune response and AEs in a vulnerable population of patients who receive cancer treatment . If subjects had not participated in this study, they would have received the same vaccine or another registered vaccine against COVID -19 according to standard of care via their general practitioner without additional testing. Version number: 6.0, 27 December 2021 24 of 49 6. INVESTIGATIONAL PRODUCT The product information of the approved mRNA -1273 SARS -CoV-2 vaccine administered to participants in this study is provided in Appendix 4 . 7. NON -INVESTIGATIONAL PRODUCT Not applicable 8. METHODS 8.1 Study parameters /endpoints 8.1.1 Main study parameter /endpoint The primary endpoint is the a ntibody based i mmune r esponse to vaccination against COVID -19 on day 28 after the second vaccination in patients receiving cancer treatment as compared to individuals without cancer . Participants will be classified as responders or non -responders. The definition of response is seroconvers ion 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 th e primary endpoint (see paragrap h 10.1) . The percentage of responders of each patient cohort will be compared with the percentage responders in the group without cancer . 8.1.2 Secondary study parameter s/endpoints  Safety assessment through: o Incidence and severity of solicited AEs during 7 days after each vaccination (see Appendix 1) o Incidence and nature of SAEs during 7 days after each vaccination o Incidence and nature of newly occurring irAEs [38] grade ≥ 3 in cohort B and D up to 28 days after the last vaccination graded according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) o Incidence, nature and severity of AESIs (see Appendix 2) graded according to CTCAE v5.0  In depth assessment of immune response through: Version number: 6.0, 27 December 2021 25 of 49 o Measurement of SARS -CoV2 specific antibodies before the second vaccination to analy ze initial response, and at 6 and 11 and 18 months after the second vaccination to measure longevity o Measurement of SARS -CoV2 specific antibodies at day 28 after the third vaccination if applicable o Assessment of SARS -CoV2 specific T cells response at 28 days after the second and third vaccination and at 6, 11 and 18 months after the second vaccination using a high throughput Interferon ɣ ELIspot 8.1.3 Exploratory study parameters  In-depth flow -cytometric analyses for functional and phenotypical characterization of SARS -CoV-2 specific cellular immune responses will be performed followed by assessment of proliferative capacity, cytokine production and phenotypical markers in a subset of patients  To determine b aseline (immune) parameters associated with immune response to COVID -19 vaccination  To assess the induction of SARS -CoV-2-specific antibodies in mucosal lining fluid  Neutralizing capacity of antibodies to test functionality .  Information on incidence of SARS -CoV-2 infection , outcome of COVID -19 will be collected and reported during 18 months after the second vaccination . To this end, questionnaires will be used. Information on positive corona tests during the study will also be collected from the RIVM .  To analyze SARS -CoV-2-binding antibody concentration after a third vaccination in pa rticipants without an adequate antibody response after two vaccinations on day 28 after the third vaccination.  To analyze safety of a third vaccination as indicated under 8.1.2  To assess SARS -CoV2 specific T ce ll response at 28 days after the third vaccination 8.2 Randomization , blinding and treatment allocation Not applicable. 8.3 Study procedures This study is executed as a low -risk intervention trial, for which no labeling is required according to Annex 13. However, the vaccine release and drug accountability will be done according to GCP. Version number: 6.0, 27 December 2021 26 of 49 Table 1: Flow chart/time and events schedu le Procedure Screeninga (within 28 days) Vacc 1 Vacc 2 Day 28 vacc 2b (± 3) Day 90 (± 7) Day 180 (± 7) Vacc 3m Day 28 vacc 3 (± 3) Day 270 (±7) Day 330 (± 14) Day 540 (± 21) Informed consent x x Inclusion/exclusion criteria x Medical history x Concomitant medication x x x x x x x x x Smoking history x ECOG PSb x Height/weight x x Vital signsc x x x x Blood testsd x x x x x x x x Nasal MLF collectione x x Sollicited adverse eventsf x x x x x SAEsg x x x x irAEsh x x x x x x AESIsi Will be reported for the entire duration of the study Vaccine administrationj x x x COVID -19 questionnairek x x x x x x x Survival status x x x a Screening should be performed within 28 days prior to the first vaccination but can be done on the same day as the first vaccination . b ECOG performance status: see appendix 3 .