Immunotherapy Resistance and Failure

Immunotherapy Resistance and Failure

A Pre-Conference Program; additional registration was required  

While many patients with cancer are experiencing significant long-term benefits from immune checkpoint inhibitors (ICIs), the vast majority exhibit either primary or secondary (acquired) resistance to these therapies. The underlying mechanisms for the wide range of responses are not well understood. Before ICI resistant/relapsed patients can be properly managed, however, these underlying causes need to be elucidated, which will enable rational design of therapeutic options based on these mechanisms of resistance. Testing of therapies in this ICI-resistant population also presents unique questions, including defining resistance and proper clinical trial design strategies.

Addressing the problem of ICI resistance and failure therefore will require collaboration between researchers and clinicians involved in all aspects of cancer research and practice, including basic, translational, and clinical areas. This program will featured both invited faculty presentations by experts in the field, as well as abstract presentations from researchers, who applied for consideration for oral presentation. These presentations were interspersed throughout the program. Session topics included defining immune checkpoint inhibitor resistance, primary resistance, secondary/acquired resistance, and therapeutic strategies for patients with resistant disease. This workshop brought together all stakeholders to address ICI resistance and failure, in order to move the field forward and continue advancing patient care.

This session used the work of the SITC Immunotherapy Resistance Committee as a foundation for discussion. The multi-stakeholder Committee has recently generated expert clinical definitions of PD-(L)1 inhibitor resistance, published in the JITC manuscript “Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce." 

Monday, Nov. 9, 2020*
9 a.m. - 3:15 p.m. EST

*Dates and times subject to change. 

Program Organizers

  • Kald Abdallah, MD, PhD – Bristol Myers Squibb
  • Edward Cha, MD, PhD – Genentech
  • Jennifer Gansert, MD, PhD – Amgen
  • Israel Lowy, MD, PhD – Regeneron Pharmaceuticals
  • Giovanni Melillo, MD – AstraZeneca
  • Eric Rubin, MD – Merck & Co., Inc.

SITC's Immunotherapy Resistance and Failure is supported in part by grants from AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Genentech, a member if the Roche Group, Incyte Corporation, and Kite, a Gilead Company.

Program Schedule

*Program schedule subject to change. 


9 a.m.  Introduction
Edward Cha, MD, PhD - Genentech
Session I: Defining Immune Checkpoint Inhibitor Resistance 
9:05 a.m. Definitions of Resistance and Gaps in Current Understanding 
Ryan J. Sullivan, MD -
Massachusetts General Hospital
9:35 a.m.

Mechanisms of Resistance and Possible New Combinations for Overcoming Them
Paolo A. Ascierto, MD - Istituto Nazionale Tumori IRCCS Fondazione Pascale

9:55 a.m. Immunotherapy Primary and Acquired Resistance
Antoni Ribas, MD, PhD - University of California Los Angeles

10:15 a.m. Break
Session II: Primary Resistance 
10:30 a.m. Approaches to Address Primary Resistance
Siwen Hu-Lieskovan, MD, PhD - Huntsman Cancer Institute, University of Utah
10:55 a.m. Neoadjuvant Immune Checkpoint Blockade: A Window into Treatment Response and Primary Resistance
Suzanne L. Topalian, MD - Johns Hopkins University School of Medicine

11:20 a.m. Coupled scRNA-seq and Intracellular Protein Activity Reveals Immune Suppressive Role of TREM2 in Cancer
Yonatan Katzenelenbogen, B.Sc - Weizmann Institute of Science
11:35 a.m. ¬MHC-I and -II Expression Levels on Tumor cells and T cell Response to Immunotherapy in B78 Murine Melanoma Model
Amy K. Erbe, PhD - University of Wisconsin
11:50 a.m. Break
Session III: Secondary/Acquired Resistance 
12:20 p.m. Approaches to Address Acquired Resistance 
Kevin J. Harrington, PhD, MD - The Institute of Cancer Research
12:45 p.m. Overcoming Acquired Resistance in anti-PD-1 Therapy by Simultaneously Depleting Tumor and All Major Types of Immunosuppressive cells
Yong Lu, PhD - Wake Forest School of Medicine
1:00 p.m. Preclinical Antitumor Activity of OncoVEXmGM-CSF in Combination with PD-1/PD-L1 Inhibitors in PD-L1 Resistant Mouse Models Supports the MASTERKEY-115 Study
Jing Qing, PhD - Amgen Inc.
1:15 p.m. Break
Session IV: Therapeutic Strategies for Patients with Resistant Disease 
1:30 p.m.
Assessment of Circulating Tumor DNA (ctDNA) and Plasma Microsatellite Instability (MSI) during PD-1 Blockade
Pashtoon M. Kasi, MD, MS - University of Iowa
1:45 p.m. Radiological Dynamics and Resistance Types in Patients with Advanced Melanoma Treated with anti-PD-1 Monotherapy
Xue Bai, MD - Peking University Cancer Hospital & MGH
2:00 p.m. Precision Microbiome Mapping Identifies a Microbiome Signature Predictive of Immune Checkpoint Inhibitor Response Across Multiple Research Study Cohorts
Matthew J. Robinson, PhD - Microbiotica
2:15 p.m. Regulatory Considerations
Marc Theoret, MD - U.S. Food and Drug Administration, OHOP
2:40 p.m.
Panel Discussion
3:10 p.m. Closing Remarks
Lowy, MD, PhD - Regeneron Pharmaceuticals

Target Audience

The target audience for this program includes researchers from academia and industry involved in basic, translational and clinical cancer research, as well as clinicians and those from regulatory and funding agencies.

Learning Objectives

At the conclusion of this activity, participants should be able to:

  • Describe patterns of both primary and acquired resistance to immune checkpoint inhibitors
  • Summarize current understanding of biological mechanisms of immune checkpoint inhibitor resistance 
  • Outline rational therapeutic strategies for patients with immune checkpoint inhibitor-resistant disease  

Presentation Application Submission

Applications for consideration to present during the Immunotherapy Resistance and Failure Pre-Conference Program opens on April 1, 2020, and are due on August 25, 2020, at 5 p.m. PDT. 

Submission Criteria

Application reviewers consider a number of variables in reviewing and selecting the applications for presentation, including, but not limited to, the following criteria:

  • Content in your presentation must be available to publicly present by Nov. 9, 2020
Presentations should address one or more of the following topics:
  • Mechanisms of immune checkpoint inhibitor resistance or failure
  • Clinical and/or translational data regarding immune checkpoint inhibitor resistance or failure
  • Therapeutic strategies for overcoming immune checkpoint inhibitor resistance or failure - with focus on specific targets and combinations
Preference will be given to presentation application submissions with the following: 
  • Has minimal overlap with other presentation applications
  • Has not been presented elsewhere or has significant changes to the submission since last being presented/published
  • Has basic research, translational and/or clinical data
This program is not eligible for continuing education credit.