COVID-19 Prevention and Treatment in Cancer; a Sequential Multiple Assignment Randomised Trial;

Inclusion Criteria:

- ARM 1:

1. Age equal to or greater than 18 years old

2. Any haematological or solid tumour

3. Signed written and verbal informed consent

4. Willingness to inform the study nurse/co-ordinator of COVID-19 testing

5. Willingness to perform a self-collect nose/throat swab

ARM 2

1. Age equal to or greater than 18 years old.

2. Any haematological or solid tumour

3. Signed written and verbal informed consent

4. Have been exposed to a known COVID-19 case within the last 72 hours, defined by the
current Department of Health and Human services such as household contact, 15 minutes
of face to face exposure, 2 hours in close space.

5. Willingness to inform the study nurse/co-ordinator of COVID-19 testing

6. Willingness to perform a self-collect nose/throat swab

ARM 3 1. Age equal to or greater than 18 years of age. 2. Any haematological or solid
tumour 3. Current or within the last 12 months received cancer related treatment such as
chemotherapy, radiotherapy or targeted small molecule, cellular therapy or
immune-modulating therapy 4. Signed written and verbal informed consent 5. Laboratory
confirmation of SARS-CoV-2 by PCR as per local laboratory assays 6. Hospitalised 7.
Symptoms of COVID-19 such as:

1. Fever equal to or greater than 38 degrees Celsius OR

2. Tachypnoea respiratory rate equal to or greater than 20 breaths/min OR

3. Pulse Oxygen saturation (SpO2) equal to or less than 94% 8. Concurrent standard of
care antimicrobials, antivirals are allowed. 9. Female and male patients of child
bearing potential will use highly effective contraception. In female child bearing
potential participants a negative urine pregnancy test will be required.

ARM 4

1. Age equal to or greater than 18 years of age.

2. Any haematological or solid tumour

3. Current or within the last 12 months received cancer related treatment such as
chemotherapy, radiotherapy or targeted small molecule, cellular therapy or
immune-modulating therapy

4. Signed written and verbal informed consent by participant or proxy capable of
giving consent

5. Laboratory virological confirmation of SARS-CoV-2 by PCR as per local laboratory
assays and COVID-19 diagnosis prior to randomisation

6. Hospitalised but has not required mechanical ventilation

7. Pneumonia diagnosed by chest x-ray or computed tomography (CT) revealing
infiltrates consistent with pneumonia and SpO2 equal to or less than 94% on room
air or requires low-flow oxygen supplementation or requires high-flow oxygen
supplementation or non-invasive positive pressure ventilation (NIPPV).

8. Has not participated in other clinical trials for COVID-19 using an
immunomodulating monoclonal antibody or kinase inhibitor. Note that participants
on dexamethasone, corticosteroids, remdesivir, convalescent plasma and/or
hydroxychloroquine with or without azithromycin are not excluded from the study.
Agents that have received emergency use authorization and/or are considered by
the study site to be standard treatment at the institution for COVID-19 are
permitted provided the agent is not an immunomodulating monoclonal antibody or
kinase inhibitor. Participation in clinical trials with remdesivir or
convalescent plasma is permitted provided that all other eligibility criteria are
met.

9. Females of childbearing potential must have a negative serum or urine pregnancy
test at screening/baseline. Women of childbearing potential must agree to use
adequate contraception (hormonal or barrier method of birth control, abstinence)
prior to study entry and for 5 months following their last dose of study drug.

Exclusion Criteria:

- ARM 1

1. Previous diagnosis of COVID-19 (microbiologically proven, either symptomatic
or asymptomatic)

2. Have been exposed to a known COVID-19 case within the last 72 hours, defined
by the current Department of Health and Human services such as household
contact, 15 minutes of face to face exposure, 2 hours in close space.

3. Any contra-indication to intra-nasal IFN-a such as severe nasal bleeding
requiring intervention, nasal malignancy, nasal deformity, radiotherapy to
the nasopharynx and/or oropharynx

4. Pregnant or breast-feeding women, or women who wish to become pregnant
during the course of the study

5. Participant unable to return for regular follow-up

6. Life expectancy of less than 4 months

7. Participant already included in another intervention study on the prevention
of COVID-19

8. Currently unwell with influenza-like symptoms - if participant is found to
be COVID-19 negative and becomes asymptomatic, they can be reconsidered for
participation

ARM 2

1. Previous diagnosis of COVID-19 (microbiologically proven, either symptomatic or
asymptomatic)

2. Any contra-indication to intra-nasal IFN-a such as severe nasal bleeding
requiring intervention, nasal malignancy, nasal deformity, radiotherapy to the
nasopharynx and/or oropharynx

3. Pregnant or breast-feeding women, or women who wish to become pregnant during the
course of the study

4. Patient unable to return for follow-up

5. Life expectancy of less than 1 month

6. Patient already included in another intervention study on the prevention of
COVID-19

7. Currently unwell with influenza-like symptoms

ARM 3

1. Unable to take oral medication

2. Any known allergic reactions to selinexor or concomitant medication-related
contra-indications to selinexor.

3. Severe critical COVID-19 infection defined as:

1. Requiring invasive or non-invasive mechanical ventilation, ECMO

2. Anticipated unlikely to survive within 48 hours

4. In the opinion of the investigator and primary oncologist, participation in the
study would not be in the best interests of the participant

5. Severe renal impairment defined as creatinine clearance (CrCL) < 20ml/min as
calculated using the Cockcroft Gault formula

6. Severe hepatic impairment defined as aspartate transaminase (AST) or alanine
transaminase (ALT) > 5 x upper limit of normal (ULN)

ARM 4

1. Invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 2.
History of pulmonary alveolar proteinosis (PAP). 3. Women of childbearing potential
who are pregnant or breastfeeding. 4. Known hypersensitivity to lenzilumab or any of
its components. 5 .Use of any FDA-approved anti-IL-6 therapy (eg. tocilizumab,
sarilumab, siltukimab), anti-IL-1 therapy (eg. anakinra, canakinumab) or kinase
inhibitor (eg.baracitinib, ibrutinib, acalabrutinib) therapy to treat COVID-19 within
8 weeks prior to randomization. Any live vaccine within 8 weeks prior to
randomisation. Note that subjects receiving other FDA-approved immunomodulators to
treat underlying autoimmune disorders such as rheumatoid arthritis, psoriasis,
ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, atopic
dermatitis, multiple sclerosis, etc. would not be excluded. Participants on
corticosteroids or dexamethasone are not excluded from the study. Note: Participants
on convalescent plasma, remdesivir and/or hydroxychloroquine with or without
azithromycin are not excluded from the study.

6. Use of GM-CSF agents (e.g., sargramostim) within 8 weeks prior to randomisation.

7. Expected survival < 24h in the opinion of the investigator. 8. Any condition that,
in the opinion of the investigator, is likely to interfere with the safety and
efficacy of the study treatment or puts the subject at unacceptably high risk from the
study.

9. Participation in another interventional study of COVID-19