COVID-19 Implications for I-O Patient Management

The purpose of this discussion thread is to share resources such as journal articles, protocols, and institutional experiences that may be of interest and value to the I-O community during the COVID-19 pandemic. When sharing a resource, simply reply to this post and include a brief description as well as the relevant web link or attached document (or both!). Documents shared in this discussion thread will be archived and freely available to viewers in the COVID-19 Patient Management discussion board library.


------------------------------
SITC Education
Society for Immunotherapy of Cancer (SITC)
Milwaukee WI
------------------------------

SITC Additional COVID-19 Resources Page

SITC has compiled a curated list of resources for immuno-oncology professionals to assist them in quickly and easily accessing the rapidly changing information on cancer care during the COVID-19 pandemic. Sourced from validated external organizations and government agencies, the resources provide general guidance for both clinicians and researchers as well as information on specific concerns for a number of disease settings. Access these additional COVID-19 resources here:

https://www.sitcancer.org/research/covid-19-resources/additionalresources

------------------------------
SITC Education
Society for Immunotherapy of Cancer (SITC)
Milwaukee WI
------------------------------

Original Message:
Sent: 05-19-2020 08:23
From: SITC Education
Subject: Shared Resources

The purpose of this discussion thread is to share resources such as journal articles, protocols, and institutional experiences that may be of interest and value to the I-O community during the COVID-19 pandemic. When sharing a resource, simply reply to this post and include a brief description as well as the relevant web link or attached document (or both!). Documents shared in this discussion thread will be archived and freely available to viewers in the COVID-19 Patient Management discussion board library.


------------------------------
SITC Education
Society for Immunotherapy of Cancer (SITC)
Milwaukee WI
------------------------------

Columbia chloroquine retrospective study

Observational study published in NEJM involving patients with COVID-19 who had been admitted to the hospital, where hydroxychloroquine administration was not associated with either a greatly lowered nor an increased risk of the composite end point of intubation or death.

https://www.nejm.org/doi/full/10.1056/NEJMoa2012410?af=R&rss=currentIssue


Resource posted on behalf of Charles G. Drake, MD, PhD – Columbia University Medical Center

------------------------------
SITC Education
Society for Immunotherapy of Cancer (SITC)
Milwaukee WI
------------------------------

Columbia famotidine retrospective study

MedRxiv pre-print of a retrospective analysis demonstrating that famotidine use is associated with reduced risk of intubation or death in hospitalized COVID-19 patients.

https://www.medrxiv.org/content/10.1101/2020.05.01.20086694v1


Resource posted on behalf of Charles G. Drake, MD, PhD – Columbia University Medical Center

------------------------------
SITC Education
Society for Immunotherapy of Cancer (SITC)
Milwaukee WI
------------------------------

Mayo Clinic randomized phase 2 trial investigating TRMPRSS2 serine protease inhibitor for COVID-19

SARS-CoV-2 has been shown to use the ACE2 and TMPRSS2 receptors for cell entry. The primary study objective is to determine if reduction in TMPRSS2 activity via direct inhibition with Camostat mesilate will decrease the rate of clinical deterioration and death as compared to standard of care for COVID-19. Camostat is a serine protease inhibitor that is currently approved in Japan for the treatment of chronic pancreatitis and reflux esophagitis and exhibits anti TMPRSS2 activity in cell line studies. Secondary objectives will include development of acute respiratory failure, time to viral clearance, time to symptomatic resolution, length of stay for hospitalized patients, time to clinical improvement (days) and clinical improvement at Day 14 (defined as a ≥ 2-point improvement from Day 1), fatality rate, survival rate at days 30 and 60, and adverse events related to treatment.

For more information, contact the study PI, Alan Haruo Bryce, MD, Bryce.Alan@mayo.edu

------------------------------
James Gulley MD, PhD, FACP
Head, Immunotherapy Section
National Cancer Institute
Bethesda MD
------------------------------

Results from Italian TOCIVID-19 clinical trial of tocilizumab

Finally we have data from TOCIVID-19 clinical trial about tocilizumab use. Analysis on 301 patients enrolled for the phase 2 study (in only 20 hours between March 19 and 20) and 920 patients enrolled later, between March 20 and 24, and coming from 185 clinical centers among all Italy.

Because of limited drug's availability at the beginning and because of the quick demand from different centers, only 60% of patients from both groups was treated with tocilizumab, in some cases even largely after their enrollment. Also, after a selection made by the centers, patients treated were in clinically worse conditions than untreated ones. They had a more severe respiratory failure and needed a more intensive respiratory assistance.

Tocilizumab effectiveness was evaluated through the mortality rate up to 14 and 30 days. At 14 days the mortality rate reported at the phase 2 was 18.4% for all patients (treated or not) and 15.6% just for those who received the drug. These data can't be considered significant, even if under 20% foreseen in advance. But data are significant up to 30 days, when the mortality rate is 22.4% in all patients and 20% just for those treated (compared to 35% expected in advance). Side effects analysis didn't show relevant signs of specific toxicity.

TOCIVID-19 clinical trial, despite limitations of a single arm study (without the control arm with placebo), suggests that tocilizumab can significantly reduce mortality up to one month, but its impact is less relevant on premature death. We hope that random phase 3 studies currently ongoing will confirm these results in the next three weeks.

Finally, it will also be interesting to extrapolate data about possible biomarkers [for instance, interleukin 6 baseline values] to check if they can be useful in selecting patients with potential benefit from treatment. Next months will keep us busy in several further data analysis.

A big thank you to Dr. Franco Perrone for his job done with great professionality and endurance and for being able to finalize in only 10 days this very important trial. Also, thank you to the Italian Medicine Agency AIFA that showed that when the game getstough, tough guys start playing. Thank you so much on behalf of the entire community, scientific or not. Last but not least, the managers Attilio Bianchi and Gerardo Botti, as well as Dr. Di Mauro, for giving us 24H support in these very busy days and foralways being at our side.

Finally, thank you to my "brother" Enzo Montesarchio, without him we could never have started this adventure.

https://www.aifa.gov.it/web/guest/-/studio-tocivid-19-risultati-incoraggianti-anche-se-non-definitivi 

------------------------------
Paolo Ascierto MD
Director
Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale'
Naples
------------------------------

Original Message:
Sent: 05-19-2020 17:01
From: James Gulley
Subject: Shared Resources

Mayo Clinic randomized phase 2 trial investigating TRMPRSS2 serine protease inhibitor for COVID-19

SARS-CoV-2 has been shown to use the ACE2 and TMPRSS2 receptors for cell entry. The primary study objective is to determine if reduction in TMPRSS2 activity via direct inhibition with Camostat mesilate will decrease the rate of clinical deterioration and death as compared to standard of care for COVID-19. Camostat is a serine protease inhibitor that is currently approved in Japan for the treatment of chronic pancreatitis and reflux esophagitis and exhibits anti TMPRSS2 activity in cell line studies. Secondary objectives will include development of acute respiratory failure, time to viral clearance, time to symptomatic resolution, length of stay for hospitalized patients, time to clinical improvement (days) and clinical improvement at Day 14 (defined as a ≥ 2-point improvement from Day 1), fatality rate, survival rate at days 30 and 60, and adverse events related to treatment.

For more information, contact the study PI, Alan Haruo Bryce, MD, Bryce.Alan@mayo.edu

------------------------------
James Gulley MD, PhD, FACP
Head, Immunotherapy Section
National Cancer Institute
Bethesda MD
------------------------------

Virtual Symposium Announcement: Cytokines in COVID-19

The NIH/FDA Immunology Interest Group and the NIH/FDA Cytokine Interest Group is holding a seminar on June 18, 2020, 9:00am - 1:45pm ET. Topics will include the dynamic cytokine response over the course of COVID-19, cellular origins of the cytokine release syndrome and cytokine-targeted mitigation strategies for COVID-19.

------------------------------
James Gulley MD, PhD, FACP
Head, Immunotherapy Section
National Cancer Institute
Bethesda
------------------------------

Original Message:
Sent: 05-20-2020 09:34
From: Paolo Ascierto
Subject: Shared Resources

Results from Italian TOCIVID-19 clinical trial of tocilizumab

Finally we have data from TOCIVID-19 clinical trial about tocilizumab use. Analysis on 301 patients enrolled for the phase 2 study (in only 20 hours between March 19 and 20) and 920 patients enrolled later, between March 20 and 24, and coming from 185 clinical centers among all Italy.

Because of limited drug's availability at the beginning and because of the quick demand from different centers, only 60% of patients from both groups was treated with tocilizumab, in some cases even largely after their enrollment. Also, after a selection made by the centers, patients treated were in clinically worse conditions than untreated ones. They had a more severe respiratory failure and needed a more intensive respiratory assistance.

Tocilizumab effectiveness was evaluated through the mortality rate up to 14 and 30 days. At 14 days the mortality rate reported at the phase 2 was 18.4% for all patients (treated or not) and 15.6% just for those who received the drug. These data can't be considered significant, even if under 20% foreseen in advance. But data are significant up to 30 days, when the mortality rate is 22.4% in all patients and 20% just for those treated (compared to 35% expected in advance). Side effects analysis didn't show relevant signs of specific toxicity.

TOCIVID-19 clinical trial, despite limitations of a single arm study (without the control arm with placebo), suggests that tocilizumab can significantly reduce mortality up to one month, but its impact is less relevant on premature death. We hope that random phase 3 studies currently ongoing will confirm these results in the next three weeks.

Finally, it will also be interesting to extrapolate data about possible biomarkers [for instance, interleukin 6 baseline values] to check if they can be useful in selecting patients with potential benefit from treatment. Next months will keep us busy in several further data analysis.

A big thank you to Dr. Franco Perrone for his job done with great professionality and endurance and for being able to finalize in only 10 days this very important trial. Also, thank you to the Italian Medicine Agency AIFA that showed that when the game getstough, tough guys start playing. Thank you so much on behalf of the entire community, scientific or not. Last but not least, the managers Attilio Bianchi and Gerardo Botti, as well as Dr. Di Mauro, for giving us 24H support in these very busy days and foralways being at our side.

Finally, thank you to my "brother" Enzo Montesarchio, without him we could never have started this adventure.

https://www.aifa.gov.it/web/guest/-/studio-tocivid-19-risultati-incoraggianti-anche-se-non-definitivi 

------------------------------
Paolo Ascierto MD
Director
Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale'
Naples

Original Message:
Sent: 05-19-2020 17:01
From: James Gulley
Subject: Shared Resources

Mayo Clinic randomized phase 2 trial investigating TRMPRSS2 serine protease inhibitor for COVID-19

SARS-CoV-2 has been shown to use the ACE2 and TMPRSS2 receptors for cell entry. The primary study objective is to determine if reduction in TMPRSS2 activity via direct inhibition with Camostat mesilate will decrease the rate of clinical deterioration and death as compared to standard of care for COVID-19. Camostat is a serine protease inhibitor that is currently approved in Japan for the treatment of chronic pancreatitis and reflux esophagitis and exhibits anti TMPRSS2 activity in cell line studies. Secondary objectives will include development of acute respiratory failure, time to viral clearance, time to symptomatic resolution, length of stay for hospitalized patients, time to clinical improvement (days) and clinical improvement at Day 14 (defined as a ≥ 2-point improvement from Day 1), fatality rate, survival rate at days 30 and 60, and adverse events related to treatment.

For more information, contact the study PI, Alan Haruo Bryce, MD, Bryce.Alan@mayo.edu

------------------------------
James Gulley MD, PhD, FACP
Head, Immunotherapy Section
National Cancer Institute
Bethesda MD
------------------------------

BTK Inhibition for COVID-19

In a prospective, off-label study, the selective Bruton tyrosine kinase inhibitor acalabrutinib was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation). Patients received 100 mg orally or per enteric feeding tube twice daily for 10 days (patients on supplemental oxygen) or 14 days (patients on mechanical ventilation). Acalabrutinib improved oxygenation in a majority of patients, often within 1-3 days of first dose with no discernable toxicities. At the end of treatment, 8/11 (72.7%) patients in the supplemental oxygen cohort were discharged on room air, and 4/8 (50%) patients in the mechanical ventilation cohort were extubated, with 2/8 (25%) discharged on room air. During treatment, serum C-reactive protein, IL-6 levels and lymphopenia normalized quickly and concomitantly with improved oxygenation.

Posted on behalf of: Louis M. Staudt, MD, PhD, and Wyndham H. Wilson, MD PhD, Lymphoid Malignancies Branch, National Cancer Institute

------------------------------
SITC Education
Society for Immunotherapy of Cancer (SITC)
Milwaukee WI
------------------------------

Original Message:
Sent: 06-05-2020 17:15
From: James Gulley
Subject: Shared Resources

Virtual Symposium Announcement: Cytokines in COVID-19

The NIH/FDA Immunology Interest Group and the NIH/FDA Cytokine Interest Group is holding a seminar on June 18, 2020, 9:00am - 1:45pm ET. Topics will include the dynamic cytokine response over the course of COVID-19, cellular origins of the cytokine release syndrome and cytokine-targeted mitigation strategies for COVID-19.

------------------------------
James Gulley MD, PhD, FACP
Head, Immunotherapy Section
National Cancer Institute
Bethesda

Original Message:
Sent: 05-20-2020 09:34
From: Paolo Ascierto
Subject: Shared Resources

Results from Italian TOCIVID-19 clinical trial of tocilizumab

Finally we have data from TOCIVID-19 clinical trial about tocilizumab use. Analysis on 301 patients enrolled for the phase 2 study (in only 20 hours between March 19 and 20) and 920 patients enrolled later, between March 20 and 24, and coming from 185 clinical centers among all Italy.

Because of limited drug's availability at the beginning and because of the quick demand from different centers, only 60% of patients from both groups was treated with tocilizumab, in some cases even largely after their enrollment. Also, after a selection made by the centers, patients treated were in clinically worse conditions than untreated ones. They had a more severe respiratory failure and needed a more intensive respiratory assistance.

Tocilizumab effectiveness was evaluated through the mortality rate up to 14 and 30 days. At 14 days the mortality rate reported at the phase 2 was 18.4% for all patients (treated or not) and 15.6% just for those who received the drug. These data can't be considered significant, even if under 20% foreseen in advance. But data are significant up to 30 days, when the mortality rate is 22.4% in all patients and 20% just for those treated (compared to 35% expected in advance). Side effects analysis didn't show relevant signs of specific toxicity.

TOCIVID-19 clinical trial, despite limitations of a single arm study (without the control arm with placebo), suggests that tocilizumab can significantly reduce mortality up to one month, but its impact is less relevant on premature death. We hope that random phase 3 studies currently ongoing will confirm these results in the next three weeks.

Finally, it will also be interesting to extrapolate data about possible biomarkers [for instance, interleukin 6 baseline values] to check if they can be useful in selecting patients with potential benefit from treatment. Next months will keep us busy in several further data analysis.

A big thank you to Dr. Franco Perrone for his job done with great professionality and endurance and for being able to finalize in only 10 days this very important trial. Also, thank you to the Italian Medicine Agency AIFA that showed that when the game getstough, tough guys start playing. Thank you so much on behalf of the entire community, scientific or not. Last but not least, the managers Attilio Bianchi and Gerardo Botti, as well as Dr. Di Mauro, for giving us 24H support in these very busy days and foralways being at our side.

Finally, thank you to my "brother" Enzo Montesarchio, without him we could never have started this adventure.

https://www.aifa.gov.it/web/guest/-/studio-tocivid-19-risultati-incoraggianti-anche-se-non-definitivi 

------------------------------
Paolo Ascierto MD
Director
Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale'
Naples

Original Message:
Sent: 05-19-2020 17:01
From: James Gulley
Subject: Shared Resources

Mayo Clinic randomized phase 2 trial investigating TRMPRSS2 serine protease inhibitor for COVID-19

SARS-CoV-2 has been shown to use the ACE2 and TMPRSS2 receptors for cell entry. The primary study objective is to determine if reduction in TMPRSS2 activity via direct inhibition with Camostat mesilate will decrease the rate of clinical deterioration and death as compared to standard of care for COVID-19. Camostat is a serine protease inhibitor that is currently approved in Japan for the treatment of chronic pancreatitis and reflux esophagitis and exhibits anti TMPRSS2 activity in cell line studies. Secondary objectives will include development of acute respiratory failure, time to viral clearance, time to symptomatic resolution, length of stay for hospitalized patients, time to clinical improvement (days) and clinical improvement at Day 14 (defined as a ≥ 2-point improvement from Day 1), fatality rate, survival rate at days 30 and 60, and adverse events related to treatment.

For more information, contact the study PI, Alan Haruo Bryce, MD, Bryce.Alan@mayo.edu

------------------------------
James Gulley MD, PhD, FACP
Head, Immunotherapy Section
National Cancer Institute
Bethesda MD
------------------------------

The National Cancer Institute (NCI) has released two Request for Applications (RFAs) for components of the new Serological Sciences Network (SeroNet). The two RFAs are for U01 Research Projects in SARS-CoV-2 Serological Sciences and U54 SARS-CoV-2 Serological Sciences Centers of Excellence. The deadline for applications is July 22, 2020, with awards anticipated to be announced in late September. 

The scope of research supported will include:

• Novel assays and model systems to test adaptive and immune response to SARS-CoV-2; 
• Understanding the mechanism underlying innate, cell-mediated, and humoral immune response to SARS-CoV-2; 
• Understanding the factors affecting the SARS-CoV-2 immune response and pathogenesis; and 
• Defining access, communication, and implementation barriers related to SARS-CoV-2 serological testing.

For those interested, NCI will be hosting a pre-application webinar on June 18^th from 1:00-2:30 p.m. that will introduce the multiple components of SeroNet and answer questions about these RFAs. More information about the webinar and registration details can be found in an upcoming notice (NOT-CA-20-074) and on NCI's Serological Sciences Network for COVID-19 webpage.

Resource posted on behalf of the National Cancer Institute

------------------------------
SITC Education
Society for Immunotherapy of Cancer (SITC)
Milwaukee WI
------------------------------

Original Message:
Sent: 06-07-2020 11:33
From: SITC Education
Subject: Shared Resources

BTK Inhibition for COVID-19

In a prospective, off-label study, the selective Bruton tyrosine kinase inhibitor acalabrutinib was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation). Patients received 100 mg orally or per enteric feeding tube twice daily for 10 days (patients on supplemental oxygen) or 14 days (patients on mechanical ventilation). Acalabrutinib improved oxygenation in a majority of patients, often within 1-3 days of first dose with no discernable toxicities. At the end of treatment, 8/11 (72.7%) patients in the supplemental oxygen cohort were discharged on room air, and 4/8 (50%) patients in the mechanical ventilation cohort were extubated, with 2/8 (25%) discharged on room air. During treatment, serum C-reactive protein, IL-6 levels and lymphopenia normalized quickly and concomitantly with improved oxygenation.

Posted on behalf of: Louis M. Staudt, MD, PhD, and Wyndham H. Wilson, MD PhD, Lymphoid Malignancies Branch, National Cancer Institute

------------------------------
SITC Education
Society for Immunotherapy of Cancer (SITC)
Milwaukee WI

Original Message:
Sent: 06-05-2020 17:15
From: James Gulley
Subject: Shared Resources

Virtual Symposium Announcement: Cytokines in COVID-19

The NIH/FDA Immunology Interest Group and the NIH/FDA Cytokine Interest Group is holding a seminar on June 18, 2020, 9:00am - 1:45pm ET. Topics will include the dynamic cytokine response over the course of COVID-19, cellular origins of the cytokine release syndrome and cytokine-targeted mitigation strategies for COVID-19.

------------------------------
James Gulley MD, PhD, FACP
Head, Immunotherapy Section
National Cancer Institute
Bethesda

Original Message:
Sent: 05-20-2020 09:34
From: Paolo Ascierto
Subject: Shared Resources

Results from Italian TOCIVID-19 clinical trial of tocilizumab

Finally we have data from TOCIVID-19 clinical trial about tocilizumab use. Analysis on 301 patients enrolled for the phase 2 study (in only 20 hours between March 19 and 20) and 920 patients enrolled later, between March 20 and 24, and coming from 185 clinical centers among all Italy.

Because of limited drug's availability at the beginning and because of the quick demand from different centers, only 60% of patients from both groups was treated with tocilizumab, in some cases even largely after their enrollment. Also, after a selection made by the centers, patients treated were in clinically worse conditions than untreated ones. They had a more severe respiratory failure and needed a more intensive respiratory assistance.

Tocilizumab effectiveness was evaluated through the mortality rate up to 14 and 30 days. At 14 days the mortality rate reported at the phase 2 was 18.4% for all patients (treated or not) and 15.6% just for those who received the drug. These data can't be considered significant, even if under 20% foreseen in advance. But data are significant up to 30 days, when the mortality rate is 22.4% in all patients and 20% just for those treated (compared to 35% expected in advance). Side effects analysis didn't show relevant signs of specific toxicity.

TOCIVID-19 clinical trial, despite limitations of a single arm study (without the control arm with placebo), suggests that tocilizumab can significantly reduce mortality up to one month, but its impact is less relevant on premature death. We hope that random phase 3 studies currently ongoing will confirm these results in the next three weeks.

Finally, it will also be interesting to extrapolate data about possible biomarkers [for instance, interleukin 6 baseline values] to check if they can be useful in selecting patients with potential benefit from treatment. Next months will keep us busy in several further data analysis.

A big thank you to Dr. Franco Perrone for his job done with great professionality and endurance and for being able to finalize in only 10 days this very important trial. Also, thank you to the Italian Medicine Agency AIFA that showed that when the game getstough, tough guys start playing. Thank you so much on behalf of the entire community, scientific or not. Last but not least, the managers Attilio Bianchi and Gerardo Botti, as well as Dr. Di Mauro, for giving us 24H support in these very busy days and foralways being at our side.

Finally, thank you to my "brother" Enzo Montesarchio, without him we could never have started this adventure.

https://www.aifa.gov.it/web/guest/-/studio-tocivid-19-risultati-incoraggianti-anche-se-non-definitivi 

------------------------------
Paolo Ascierto MD
Director
Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale'
Naples

Original Message:
Sent: 05-19-2020 17:01
From: James Gulley
Subject: Shared Resources

Mayo Clinic randomized phase 2 trial investigating TRMPRSS2 serine protease inhibitor for COVID-19

SARS-CoV-2 has been shown to use the ACE2 and TMPRSS2 receptors for cell entry. The primary study objective is to determine if reduction in TMPRSS2 activity via direct inhibition with Camostat mesilate will decrease the rate of clinical deterioration and death as compared to standard of care for COVID-19. Camostat is a serine protease inhibitor that is currently approved in Japan for the treatment of chronic pancreatitis and reflux esophagitis and exhibits anti TMPRSS2 activity in cell line studies. Secondary objectives will include development of acute respiratory failure, time to viral clearance, time to symptomatic resolution, length of stay for hospitalized patients, time to clinical improvement (days) and clinical improvement at Day 14 (defined as a ≥ 2-point improvement from Day 1), fatality rate, survival rate at days 30 and 60, and adverse events related to treatment.

For more information, contact the study PI, Alan Haruo Bryce, MD, Bryce.Alan@mayo.edu

------------------------------
James Gulley MD, PhD, FACP
Head, Immunotherapy Section
National Cancer Institute
Bethesda MD
------------------------------