CHAPTER 8: Cancer Immunotherapy Survey All (N=100) Please classify your organization. Academic lab or center Small biopharmaceutical company Top 20 Pharma Mid-size pharma Diagnostics company Other (please specify) Government or NGO research center Contract research organization (CRO) 30% 18% 16% 7% 6% 5% 5% Do you work in any aspect of discovery and development of cancer immunotherapies? Antibody checkpoint inhibitors Biomarker identification and/or clinical testing Cytokines Adoptive immunotherapy with tumor infiltrating lymphocytes (TILs) Adoptive immunotherapy with chimeric antigen receptor T-cells (CAR T-cells) Dendritic cell cancer vaccines DNA plasmid vaccines 52% 36% 21% 12% 9% 3% 183
All (N=100) What types of agents do you work on? Small-molecule checkpoint inhibitors Other small-molecule immunomodulators Peptide or protein cancer vaccines Personalized T-cell therapies that target neoantigens Personalized neoantigen vaccines 24% 23% 19% 9% 2% What is your role in developing and/or using cancer immunotherapy agents? Laboratory researcher Clinician (treat patients in clinical trials and/or in medical practice) I am not involved in developing and/or using cancer immunotherapy agents 59% 10% 2% According to a 2014 news article in Nature, immunotherapies may comprise a U.S. $35 billion market by 2024, and be used in 60% of cases of advanced cancer. Do you agree? Recent clinical studies with checkpoint inhibitors that target PD-1 (BMS nivolumab Opdivo) and Merck s pembrolizumab (Keytruda) and CT- LA-4-targeting drug ipilimumab (Yervoy) indicate that these drugs promote survival in an increasing number of types of previously untreatable advanced cancer (e.g., melanoma, lung cancers, kidney cancer, Merkel cell carcinoma, colorectal cancer, liver cancer). However, these drugs do not benefit all patients with these cancers, nor do they induce long-term survival in all patients. Do you agree with the assessment that where we are with checkpoint inhibitor treatment in 2016 is similar to where we were with chemotherapy in the 1960s, when we were just beginning to use it? Yes 83% decline to answer Yes 65% No 24% decline to answer 11% Do you believe that combining a checkpoint inhibitor with another checkpoint inhibitor, another immunotherapeutic (e.g. a cancer vaccine or T-cell therapy), with radiation, chemotherapy, or surgery, or with targeted therapies might give improved results? It depends on the particular combination and the particular type of cancer 50% Yes 38% We need more data from the initial studies of this type 9% decline to answer 2% Which of the following potential prognostic biomarkers for use with checkpoint inhibitors are you familiar with? PD-L1 expression 57% Measurement of the immunoscore (measurement of immune cell infiltration in and around tumors 22% Measurement of mutational load in tumor DNA 11% Measurement of defects in DNA repair genes in tumor DNA 10% 184
Do you believe that research on biomarkers such as those listed in question 9 can result in improved treatments with checkpoint inhibitors, including the ability to use these drugs to more effectively treat cancers other than melanoma and non-small cell lung cancer (NSCLC)? Yes 67% Too early to tell 25% Do you believe that the intense competition in the checkpoint inhibitor field will result in lowering the costs to patients and payers of these expensive therapies? Yes 44% No 17% Too early to tell 32% decline to answer 7% Do you believe that there is a need to discover and develop drugs to educate immune cells to attack and infiltrate tumors, in the case of tumors with low immunoscores? Yes 86% decline to answer 11% Do you believe that the expected high cost of combination therapies for cancer will limit their use? Yes 60% No 16% Too early to tell 19% In May 2016, Roche/Genentech s atezolizumab (trade name Tecentriq, formerly known as MPDL3280A), a checkpoint inhibitor antibody that targets PD-L1, was approved by the FDA for treatment of advanced urothelial bladder cancer. Atezolizumab also received priority review from the FDA for treatment of patients with PD-L1 positive advanced NSCLC, and may be approved by October 2016. Do you believe that atezolizumab will become a successful immunotherapy drug like the three previously-approved checkpoint inhibitors in the next several years? Yes 16% No 9% It depends on the cancer being treated 33% Too early to tell 34% decline to answer 8% Yes 51% Too early to tell 43% Do you believe that anti-pd-l1 agents such as atezolizumab will prove to be superior to both anti- CTLA-4 and anti-pd-1 agents, in terms of efficacy and safety? Do you believe that regulatory agencies concerned with limiting costs (such as the U.K. s NICE or the U.S. Independent Payment Advisory Board) are likely to limit the use of expensive immunotherapies for cancer, especially combination therapies? In October 2015, the FDA approved the first oncolytic virus immunotherapy, Amgen s Imlygic (talimogene laherparepvec), for local treatment of unresectable cutaneous, subcutaneous and nodal lesions in patients with melanoma recurrent after initial surgery. Researchers are now working on development of other oncolytic virus therapies, often in combinations with other types of immunotherapy. Do you believe that oncolytic viruses will be successful anti-cancer therapies within the next ten years? Yes 48% No 12% Too early to tell 28% decline to answer 12% Yes 42% Too early to tell 44% decline to answer 11% 185
Do you believe that anti-cancer vaccines will be successful anticancer therapies within the next ten years? Yes 41% Not as stand-alone therapies, but only in combination therapies 23% Too early to tell 28% decline to answer 4% Do you believe that companies have been developing adequate mean to manufacture personalized CD19-targeting CAR T-cell therapies for ALL, for a commercialization target date of 2017-2018? Yes 31% No 21% Too early to tell 19% decline to answer 29% Do you believe that creating personalized anti-cancer vaccines that target tumorspecific neoatigens will be a more successful approach to cancer treatment than previous types of vaccines that have had a high rate of clinical failure? Yes 56% No 5% decline to answer 10% Do you believe that companies can make CAR T-cell therapy for B-cell malignancies reimbursable and commercially viable? Yes 40% No 6% decline to answer 25% Do you believe that a CD19- targeting CAR T-cell therapy for treatment of B-cell acute lymphoblastic leukemia (ALL) and/or other B-cell leukemias or lymphomas (developed by such companies as Novartis/University of Pennsylvania, Juno and/or Kite) will reach the market by 2017? Yes 37% No 16% Too early to tell 25% decline to answer 22% Do you believe that researchers and companies (e.g., Juno, Medigene, Neon) will be able to create successful and commercializable adoptive immunotherapies based on recombinant T-cell receptors, in addition to CARs? Yes 45% Too early to tell 36% decline to answer 15% Do you believe that researchers and companies have developed adequate means to overcome the severe adverse effects seen in some patients treated with CAR T-cell therapy? Yes 24% No 22% Too early to tell 38% decline to answer 16% Do you believe that T-cell-based adoptive immunotherapies (e.g., CAR, recombinant T-cell receptors) will be useful in treating solid tumors, or only hematologic malignancies? Both solid and hematologic 47% Hematologic only 18% decline to answer 6% 186
Do you believe that bispecific antibody drugs will prove superior to corresponding CAR T-cell drugs, because of their greater ease of manufacturing and their potential for improved safety? Yes 34% Too early to tell 20% It depends on the specific cancer and/or the state of the patient s immune system (e.g., T-cell depletion) 35% decline to answer 10% 187