ASCO17: Day 3 Immunotherapy Highlights

Day 3 at the 2017 annual meeting of the American Society of Clinical Oncology touched on immunotherapy combinations and the promise of several novel immunotherapies, including anti-IDO1 checkpoint blockade and a personalized, patient-specific vaccine. Other measures of immunotherapy’s effectiveness, such as patient quality of life, were also discussed. Below are some of the most important findings that were revealed today:

Multiple Tumor Types:

• In a phase I clinical trial, the checkpoint immunotherapy combination of GDC-0919 (anti-IDO1) and atezolizumab (anti-PD-L1) was able to dampen IDO1 activity and showed early signs of effectiveness in patients with advanced/metastatic solid tumors.
• In a phase I/II clinical trial, the combination of BMS-986156 (GITR agonist antibody immunotherapy) and nivolumab (anti-PD-1 checkpoint immunotherapy) demonstrated anti-tumor activity in patients with advanced solid tumors.
• A correlation was found between the number and size of tumor-associated macrophages (TAMs) and overall survival in patients regardless of the stage of their disease.

Bladder Cancer:

• In a phase III clinical trial, advanced bladder cancer patients treated with pembrolizumab (anti-PD-1 checkpoint immunotherapy) experienced significantly better health-related quality of life and increased overall survival compared to those treated with chemotherapy. (Lawrence Fong, M.D., was involved in this work.) >

Brain Cancer:

• In a phase I clinical trial, DNX-2401 (oncolytic adenovirus immunotherapy) demonstrated promise in patients with recurrent glioblastoma.
• In a phase III clinical trial, a personalized peptide vaccine demonstrated clinical efficacy in patients with HLA-A24+ glioblastoma.

Breast Cancer:

• In a phase II clinical trial, pre-surgery treatment with the combination of dual anti-HER2 antibody immunotherapies (pertuzumab and trastuzumab) along with chemotherapy led to a 78% pathologic complete response rate in patients with either early or late-stage HER2+/ER- breast cancer.
• In a phase I clinical trial, ZW25 (a bi-specific antibody immunotherapy that can target two different components of HER2) demonstrated effectiveness in patients with HER2+ breast cancer.

Esophageal Cancer:

• In a phase I/II clinical trial, the checkpoint immunotherapy combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) provided long-term survival benefits in patients with advanced/metastatic gastroesophageal cancer. (Dung T. Le, M.D., was the senior author of this work, in which Padmanee Sharma, M.D., and Dirk Jaeger, M.D., were also involved.)

Head and Neck Cancer:

• The combination of cetuximab (anti-EGFR antibody immunotherapy) and chemotherapy appeared to promote antitumor activity in patients with head and neck squamous cell carcinoma (HNSCC) with poor performance status, and its effectiveness was often accompanied by a decrease in certain immunosuppressive microRNAs in the saliva of patients.

Kidney Cancer:

• In a phase I clinical trial, the combination of AM0010 (PEGylated IL-10 cytokine immunotherapy) and nivolumab (anti-PD-1 checkpoint immunotherapy) appeared to activate killer T cells and promote anti-tumor activity in patients with kidney cancer. (Nizar M. Tannir, M.D., FACP, was involved in this work.)
• In a phase I/II clinical trial, the checkpoint immunotherapy combination of epacadostat (anti-IDO1) and pembrolizumab (anti-PD-1) led to promising responses in patients with kidney cancer as both a first-line and second-line treatment. (Thomas F. Gajewski, M.D., Ph.D. was involved in this work.)

Leukemia:

• Combining pembrolizumab (anti-PD-1 checkpoint immunotherapy) with anti-CD19 CAR (chimeric antigen receptor) T cell immunotherapy enhanced survival of the transplanted CAR T cells and led to clinical responses in pediatric patients with relapsed acute lymphoblastic leukemia (ALL). (Carl H. June, M.D., was involved in this work.)
• In a phase II clinical trial, CAR (chimeric antigen receptor) T cell immunotherapy was associated with significantly improved quality of life, in addition to an 82% complete response rate, in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia.

Lung Cancer:

• In a phase II clinical trial, trastuzumab emtansine (anti-HER2 antibody-drug conjugate immunotherapy) led to several responses in patients with HER2-overexpressing advanced/metastatic non-small cell lung carcinoma (NSCLC).
• A relationship between EGFR pathway activation, increased CD73 expression, and decreased IFN-gamma expression was found in patients with non-small cell lung carcinoma, and could possibly explain the lack of benefit associated with anti-PD-1/PD-L1 checkpoint immunotherapy in these patients.

Melanoma / Skin Cancers:

• In a phase II clinical trial, the checkpoint immunotherapy combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) was effective against symptomatic brain metastases in patients with metastatic melanoma and was associated with higher response and survival rates compared to nivolumab alone. (Georgina V. Long, M.D., Ph.D., gave the oral presentation of this work, in which Richard A. Scolyer, M.D., was also involved.)
• In another phase II clinical trial, the checkpoint immunotherapy combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) was effective against asymptomatic brain metastases in patients with metastatic melanoma and was associated with higher response and survival rates compared to nivolumab alone. This approach could potentially offer an alternative to radiation therapy for these patients. (Michael A. Postow, M.D., was involved in this work.)
• In a phase III clinical trial, pembrolizumab (anti-PD-1) provided lasting benefits in patients with advanced melanoma, and was associated with a relatively low (9%) risk of disease progression or death almost a year after finishing treatment. (Antoni Ribas, M.D., Ph.D., was the senior author of this work, in which (Georgina V. Long, M.D., Ph.D., was also involved.)
• In a phase I clinical trial, REGN2810 (anti-PD-1 checkpoint immunotherapy) demonstrated anti-tumor efficacy in patients with advanced/metastatic cutaneous squamous cell carcinoma (CSCC). (Israel Lowy, M.D., Ph.D., was involved in this work.)

Sarcoma:

• In a phase I/II clinical trial, cabiralizumab (anti-CSF1R immunomodulator therapy) showed promising activity in patients with tenosynovial giant cell tumor (TGCT).

Stomach & Gastrointestinal Cancer:

• In a phase I/II clinical trial, the checkpoint immunotherapy combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) provided long-term survival benefits in patients with advanced/metastatic gastroesophageal cancer. (Dung T. Le, M.D., was the senior author of this work, in which Padmanee Sharma, M.D., and Dirk Jaeger, M.D., were also involved.)