ASCO17: Days 4 and 5 Immunotherapy Highlights

Day 1 at the 2017 annual meeting of the American Society of Clinical Oncology demonstrated immunotherapy’s potential to help in treating many different types of cancers. Here are some highlights from data and learnings presented in Chicago.

Multiple Tumor Types:

• In a phase I/II clinical trial, the combination of nivolumab (anti-PD-1 checkpoint immunotherapy) and NKTR-214 (an engineered IL-2 cytokine that activates CD122) demonstrated early signs of clinical efficacy in patients with advanced or metastatic solid tumors. (Nizar M. Tannir, M.D., FACP, and Patrick Hwu, M.D., were involved in this work.) http://abstracts.asco.org/199/AbstView_199_185207.html
• Patients with persistent lymphopenia (decreased numbers of immune cells) appear to be less likely to respond to anti-PD-1 checkpoint immunotherapy. (Elizabeth M. Jaffee, M.D., was involved in this work.) http://abstracts.asco.org/199/AbstView_199_187589.html

Bladder Cancer:

• Alterations in the genes responsible for DNA damage repair (DDR), which are associated with higher mutational loads in tumors, was associated with significantly improved responses in patients with metastatic bladder cancer who were treated with anti-PD-1/PD-L1 checkpoint immunotherapy. (Jedd D. Wolchok, M.D., Ph.D., was involved in this work.) http://abstracts.asco.org/199/AbstView_199_191279.html
• A new tool—the MSI Sensor assay—can help doctors determine the extent to which tumors have deficient DNA mismatch repair (MMR) capability, which is associated with durable responses to checkpoint immunotherapy in patients with advanced bladder cancer. http://abstracts.asco.org/199/AbstView_199_190640.html

Brain Cancer:

• Dendritic cell-based immunotherapy was associated with improved survival in stage IV glioblastoma patients who failed first-line therapy. One patient who didn’t respond to the treatment was then treated with nivolumab, and has remained alive almost 7 years. http://abstracts.asco.org/199/AbstView_199_192154.html
• D2C7-IT, which contains EGFR-targeting antibodies attached to a toxin, was able to be safely administered to patients with advanced glioma, and has shown “encouraging results.” http://abstracts.asco.org/199/AbstView_199_192413.html

Breast Cancer:

• Treating patients with the combination of two anti-HER2 antibody immunotherapies (trastuzumab and pertuzumab) along with a standard chemotherapy regimen before surgery was safe and highly effective for patients with HER2+ early breast cancer. http://abstracts.asco.org/199/AbstView_199_190386.html
• The radiolabeled ⁶⁴Cu-DOTA-trastuzumab was able to predict responses to treatment with ado-trastuzumab emtansine (an anti-HER2 antibody immunotherapy) in patients with HER2+ metastatic breast cancer. http://abstracts.asco.org/199/AbstView_199_193302.html

Cervical Cancer:

• In a phase I/II clinical trial, 20.8% of patients with recurrent/metastatic cancer (cervical, vaginal, or vulvar) responded to nivolumab (anti-PD-1 immunotherapy) treatment, in addition to a 70.8% disease control rate. These responses occurred in both HPV+/- patients, and in tumors both with and without PD-L1 expression. http://abstracts.asco.org/199/AbstView_199_184153.html

Childhood Cancer:

• In a multicenter study in China, CD19 CAR (chimeric antigen receptor) T cell immunotherapy led to complete responses in 73% (8/11) of children with relapsed/refractory acute lymphocytic leukemia (ALL). http://abstracts.asco.org/199/AbstView_199_191833.html

Colorectal Cancer:

• A vaccine made from patients’ own tumor cells—which are modified so that they have increased expression of the pro-immune GM-CSF but decreased expression of the immunosuppressive TGF-beta—was capable of promoting a systemic immune response in combination with chemotherapy, and produced long term responses in several patients. http://abstracts.asco.org/199/AbstView_199_187652.html
• Lower levels of pro-tumor macrophage infiltration were associated with improved responses in patients with advanced colorectal cancer treated with bevacizumab (anti-VEGF antibody immunotherapy), and could serve as a useful biomarker in the future. http://abstracts.asco.org/199/AbstView_199_188312.html

Esophageal Cancer:

• The pre-treatment expression of certain microRNAs was able to predict which patients with esophageal cancer would respond to nivolumab (anti-PD-1 checkpoint immunotherapy). http://abstracts.asco.org/199/AbstView_199_187376.html
• In a phase II clinical trial, a peptide-based cancer vaccine was able to induce strong anti-tumor immune responses and was better at preventing relapse after surgery (compared to the control) in patients with esophageal cancer. http://abstracts.asco.org/199/AbstView_199_187804.html

Head and Neck Cancer:

• The combination of rAd-p53 (a recombinant virus designed to transfer the p53 gene into tumor cells) and radiation therapy was shown to decrease both recurrence and metastasis, and increase the disease-free survival rate, over a 7-year follow up period in patients with thyroid cancer. http://abstracts.asco.org/199/AbstView_199_181430.html
• Improved survival was observed in patients with hypopharyngeal cancer whose tumors lacked PD-L1 expression and were heavily infiltrated by killer T cells. http://abstracts.asco.org/199/AbstView_199_182347.html

Kidney Cancer:

• In a phase I clinical trial, pembrolizumab (anti-PD-1 immunotherapy) in combination with radiation therapy led to multiple responses, which were associated with fewer monocytes compared to non-responders. http://abstracts.asco.org/199/AbstView_199_191243.html

Leukemia:

• CAR (chimeric antigen receptor) T cells targeting the CD19 receptor led to complete responses in two patients with relapsed acute lymphoblastic leukemia (ALL). http://abstracts.asco.org/199/AbstView_199_192547.html
• Patients with relapsed/refractory acute lymphoblastic leukemia (ALL) who were treated with inotuzumab ozogamicin (an anti-CD22 antibody immunotherapy attached to a toxin) experienced shorter hospital stays after treatment compared to ALL patients treated with the standard of care.  http://abstracts.asco.org/199/AbstView_199_194173.html
• Patients with relapsed/refractory acute lymphoblastic leukemia (ALL) who were treated with inotuzumab ozogamicin (an anti-CD22 antibody immunotherapy attached to a toxin) experienced an average increase of 2 years in their overall survival adjusted for quality of life. http://abstracts.asco.org/199/AbstView_199_193642.html

Liver Cancer:

• Compared to patients with liver cancer who were treated with surgery alone, liver cancer patients who received cytokine-induced killer (CIK) cells after surgery had significantly improved survival, overall and disease-free, both of which were associated with an increased number of PD-1+ tumor-infiltrating cells. http://abstracts.asco.org/199/AbstView_199_189091.html

Lung Cancer:

• In a 3-D system using patient-derived non-small cell lung carcinoma (NSCLC) cells, the combination of bavituximab (anti-phosphatidylserine antibody) and nivolumab (anti-PD-1 checkpoint inhibitor) led to enhanced immune responses compared to either immunotherapy alone. (Scott J. Antonia, M.D., Ph.D., was involved in this work.) http://abstracts.asco.org/199/AbstView_199_193973.html
• In a 3-D system using patient-derived non-small cell lung carcinoma (NSCLC) cells, both nivolumab and pembrolizumab (anti-PD-1 checkpoint immunotherapies) individually promoted anti-tumor macrophage activity and T cell activation. (Scott J. Antonia, M.D., Ph.D., was involved in this work.) http://abstracts.asco.org/199/AbstView_199_193442.html
• In patients with metastatic non-small cell lung carcinoma (NSCLC) who were treated with anti-PD-1/PD-L1 checkpoint immunotherapy, those who responded were much more likely to exhibit early proliferation of PD-1+ killer T cells in their peripheral blood compared to non-responders. (Rafi Ahmed, Ph.D., who sponsors CRI postdoctoral fellow William H. Hudson, Ph.D., was involved in this work.) http://abstracts.asco.org/199/AbstView_199_193150.html

Lymphoma:

• CAR (chimeric antigen receptor) T cells targeting the CD19 receptor led to complete responses in two patients with relapsed diffuse large B cell lymphoma (DLBCL). http://abstracts.asco.org/199/AbstView_199_192547.html

Melanoma:

• The combination of nivolumab (anti-PD-1 checkpoint immunotherapy) and ipilimumab (anti-CTLA-4 checkpoint immunotherapy) was able to help control melanoma in patients whose diseased progressed after previous single-agent checkpoint immunotherapy. (Craig L. Slingluff Jr., M.D., was involved in this work.) http://abstracts.asco.org/199/AbstView_199_188559.html
• In immunotherapy-treated patients with metastatic melanoma, larger tumors were more resistant to anti-PD-1 checkpoint immunotherapy, but not the combination of anti-PD-1 and anti-CTLA-4 checkpoint immunotherapy. http://abstracts.asco.org/199/AbstView_199_194751.html

Ovarian Cancer:

• Pre-surgical treatment with bevacizumab (anti-VEGF antibody immunotherapy) in combination with chemotherapy was associated with improved surgical outcomes in patients with advanced, initially unresectable ovarian cancer. http://abstracts.asco.org/199/AbstView_199_186640.html

Pancreatic Cancer:

• The combination of REOLYSIN (oncolytic reovirus immunotherapy) and pembrolizumab (anti-PD-1 checkpoint immunotherapy) along with chemotherapy demonstrated anti-cancer activity in patients with metastatic and relapsed pancreatic cancer. http://abstracts.asco.org/199/AbstView_199_193345.html

Prostate Cancer:

• Expression of the cancer-testis antigen NY-ESO-1 was observed in almost one-third of the prostate cancer patients that were analyzed, suggesting that it could serve as a promising target for immunotherapy. (Kunle Odunsi, M.D., Ph.D., was involved in this work.

Sarcoma:

• In a phase II clinical trial, the combination of the checkpoint immunotherapies nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) led to responses in patients with several different types of metastatic sarcoma. http://abstracts.asco.org/199/AbstView_199_184079.html
• In a phase I clinical trial, the immunotherapy vaccine CMB305 (whose dual components seek to elicit an immune response against NY-ESO-1) was able to induce strong immune responses, including antigen spreading, in patients with recurrent NY-ESO-1+ soft tissue sarcoma. (Sacha Gnjatic, Ph.D., and Patrick Hwu, M.D., were involved in this work.) http://abstracts.asco.org/199/AbstView_199_191129.html
• Pembrolizumab (anti-PD-1 checkpoint immunotherapy) led to responses in patients with various types of soft tissue sarcomas, including a 40% response rate in patients with undifferentiated pleomorphic sarcoma (UPS). http://abstracts.asco.org/199/AbstView_199_192958.html

Stomach & Gastrointestinal Cancer:

• In 99 cases of cholangiocarcinoma, 92% were found to express mesothelin, and the patients whose tumors had low mesothelin expression as well as low infiltration of killer T cells were found to have the poorest prognosis. (Craig L. Slingluff Jr., M.D., was involved in this work.) http://abstracts.asco.org/199/AbstView_199_194002.html
• Treatment with pembrolizumab (anti-PD-1 checkpoint immunotherapy) led to responses in several patients with mismatch repair-deficient (dMMR) gastrointestinal cancer, including one patient with cholangiocarcinoma who has a complete response.

Other:

• An online tool was developed to help healthcare providers deal with immune-related adverse events after immunotherapy. Thus far the tool has recommended an alternative course of action in 49% of queries, and 93% of healthcare providers said that they incorporated this advice into their decision making. (Jeffrey S. Weber, M.D., was involved in this work.) http://abstracts.asco.org/199/AbstView_199_190591.html