ASCO17: Day 2 Immunotherapy Highlights

Day 2 at the 2017 annual meeting of the American Society of Clinical Oncology further highlighted immunotherapy's potential to treat many of the most common types of cancer. Here is an overview of the data coming out of today's session:

Multiple Tumor Types:

• Measuring the levels of soluble PD-L1 and Bim+ killer T cells through non-invasive blood draws appeared able to help doctors predict as well as monitor responses after anti-PD-1 checkpoint immunotherapy in patients with melanoma and lung cancer. (Haidong Dong, MD, PhD, was involved in this work.) https://abstracts.asco.org/199/AbstView_199_193960.html  

Bladder Cancer:

• In a phase I/II clinical trial, the amount of circulating tumor DNA in the blood soon after treatment with durvalumab (anti-PD-L1 checkpoint immunotherapy) decreased in patients who responded, and was associated with increased survival (both overall and progression-free survival). https://abstracts.asco.org/199/AbstView_199_184983.html

Brain Cancer:

• SBT-100 (a bi-specific antibody immunotherapy that targets both KRAS and P-STAT3) was able to inhibit the growth of glioblastoma cells in vitro, and was able to cross the blood-brain barrier in mice. https://abstracts.asco.org/199/AbstView_199_188416.html

Breast Cancer:

• In a phase II clinical trial, pembrolizumab (anti-PD-1 checkpoint immunotherapy) led to durable responses in some heavily pre-treated patients with metastatic triple-negative breast cancer (TNBC). https://abstracts.asco.org/199/AbstView_199_190305.html
• In a phase III clinical trial, the immunotherapy trastuzumab emtansine (anti-HER antibody with a toxin attached) was shown to be an effective first-line treatment for patients with HER2+ metastatic breast cancer, and exhibited fewer severe adverse events and an increased median overall survival compared to the standard trastuzumab (anti-HER2 antibody immunotherapy) plus chemotherapy regimen. https://abstracts.asco.org/199/AbstView_199_185945.html
• In a phase II clinical trial, the combination of pembrolizumab (anti-PD-1 checkpoint immunotherapy) and chemotherapy was able to stimulate immune responses that led to clinical benefits in multiple patients with metastatic triple-negative breast cancer (TNBC). https://abstracts.asco.org/199/AbstView_199_194049.html   

Cervical Cancer:

• In a phase I/II clinical trial, an anti-HPV type 16 vaccine in combination with chemotherapy was able to elicit immune responses against HPV antigens in some patients with HPV16+ cervical cancer, and stronger immune responses were correlated increased overall survival. (Cornelis J. M. Melief, MD, PhD, was involved in this work.) https://abstracts.asco.org/199/AbstView_199_192139.html

Childhood Cancer:

• CAR (chimeric antigen receptor) T cells targeting the CD19 receptor were effective at promoting long-term responses in pediatric patients with extramedullary relapse of their acute lymphoblastic leukemia (ALL). (Carl H. June, MD, was involved in this work.) https://abstracts.asco.org/199/AbstView_199_193305.html
• In a phase I clinical trial, CAR (chimeric antigen receptor) T cells targeting the HER2 receptor appeared safe and led to clinical benefit in several patients with HER2+ sarcoma. https://abstracts.asco.org/199/AbstView_199_194365.html

Colorectal Cancer:

• In a phase II clinical trial, the combination of pembrolizumab (anti-PD-1 checkpoint immunotherapy) and chemotherapy demonstrated promise as a first-line treatment for patients with advanced colorectal cancer, even for patients whose tumors were DNA mismatch repair proficient (pMMR). https://abstracts.asco.org/199/AbstView_199_183499.html
• In a phase II clinical trial, dual checkpoint immunotherapy with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) led to high rates of response and disease control in patients with MSI-hi / DNA mismatch repair deficient (dMMR) colorectal cancer. https://abstracts.asco.org/199/AbstView_199_185252.html

Esophageal Cancer:

• In a phase I clinical trial, the combination of pembrolizumab (anti-PD-1 checkpoint immunotherapy) and ramucirumab (anti-VEGFR2 antibody immunotherapy) showed promise in patients with gastroesophageal junction adenocarcinoma, both as a first-line treatment and after previous treatment with other therapies. https://abstracts.asco.org/199/AbstView_199_184481.html
• The presence of microsatellite instability (MSI) or high mutational load (>10 mutations / million base pairs) in the tumors of esophagogastric cancer patients were much more likely to benefit from immunotherapy (either anti-PD-1/PD-L1 checkpoint immunotherapy, or combined anti-PD-1/PD-L1 + anti-CTLA-4 checkpoint immunotherapy). https://abstracts.asco.org/199/AbstView_199_191437.html

Leukemia:

• CAR (chimeric antigen receptor) T cells targeting the CD19 receptor were effective at promoting long-term responses in pediatric patients with extramedullary relapse of their acute lymphoblastic leukemia (ALL). (Carl H. June, MD, was involved in this work.) https://abstracts.asco.org/199/AbstView_199_193305.html
• In a phase III clinical trial, the combination of ublituximab (anti-CD20 antibody immunotherapy) and chemotherapy led to more patient responses compared to chemotherapy alone, and did so without significantly increased toxicity. https://abstracts.asco.org/199/AbstView_199_189901.html

Liver Cancer:

• In a phase I/II clinical trial, durvalumab (anti-PD-1 checkpoint immunotherapy) showed evidence of clinical benefit, disease control, and improved survival in patients with liver cancer, especially those with hepatitis C infected tumors. (Scott J. Antonia, MD, PhD, Dirk Jaeger, MD, and Neil H. Segal, MD, PhD, were involved in this work.)  https://abstracts.asco.org/199/AbstView_199_186923.html
• In a phase I/II clinical trial, nivolumab (anti-PD-1 checkpoint immunotherapy) led to sustained benefits and increased survival in patients with advanced liver cancer, whether or not they had been previously treated with the chemotherapy sorafenib. https://abstracts.asco.org/199/AbstView_199_185284.html

Lung Cancer:

• In a phase I clinical trial, first-line treatment with the checkpoint immunotherapy combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) was effective for patients with advanced non-small cell lung carcinoma (NSCLC), resulting in six complete responses. Patients whose tumors expressed high levels of PD-L1 were more likely to benefit, but even some patients with minimal PD-L1 expression experienced complete responses. (This work involved Scott J. Antonia, MD, PhD, and Julie R. Brahmer, MD) https://abstracts.asco.org/199/AbstView_199_184051.html
• In a phase I/II clinical trial, the checkpoint immunotherapy combination of epacadostat (anti-IDO1) and pembrolizumab (anti-PD-1) provided benefits for patients with non-small cell lung carcinoma (NSCLC). https://abstracts.asco.org/199/AbstView_199_181148.html
• In a phase I clinical trial, the combination of AM0010 (PEGylated IL-10 cytokine immunotherapy) and pembrolizumab (anti-PD-1 checkpoint immunotherapy) was effective at activating killer T cells and demonstrated clinical activity in patients with advanced non-small cell lung carcinoma (NSCLC). https://abstracts.asco.org/199/AbstView_199_189952.html
• In a phase II clinical trial, pembrolizumab (anti-PD-1 checkpoint immunotherapy) led to a 21% response rate and an 80% disease control rate in patients with mesothelioma, regardless of PD-L1 expression. https://abstracts.asco.org/199/AbstView_199_191066.html

Melanoma:

• In a phase I/II clinical trial, the checkpoint immunotherapy combination of BMS-986016 (anti-LAG-3) and nivolumab (anti-PD-1) showed promise in patients with metastatic melanoma that progressed after prior anti-PD-1 immunotherapy treatment. (Thomas F. Gajewski, MD, PhD, was involved in this work.) (https://abstracts.asco.org/199/AbstView_199_184185.html
• In a phase I/II clinical trial, the checkpoint immunotherapy combination of pembrolizumab (anti-PD-1) and ipilimumab (anti-CTLA-4) demonstrated long-term benefits in patients with advanced melanoma. (Georgina V. Long, MD, PhD, was the senior author on this work, in which Jonathan Cebon, PhD, FRACP, and Antoni Ribas, MD, PhD, were also involved.)   https://abstracts.asco.org/199/AbstView_199_190321.html
• In a phase I/II clinical trial, the combination of SD-101 (TLR9 agonist immunotherapy) and pembrolizumab (anti-PD-1 checkpoint immunotherapy) appeared to promote anti-tumor immune activity in metastatic melanoma patients. (Antoni Ribas, MD, PhD, was the senior author of this work) https://abstracts.asco.org/199/AbstView_199_193149.html
• In a phase II clinical trial, resiquimod (TLR 7/8 agonist immunotherapy) was able to effectively enhance anti-tumor immune activity in patients with metastatic melanoma. (Patrick Hwu, MD, was the senior author of this work.) https://abstracts.asco.org/199/AbstView_199_186011.html
• In a phase I clinical trial, the checkpoint immunotherapy combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) was effective as a pre-surgery treatment for patients with high-risk stage III melanoma. (Ton N. Schumacher, PhD, was the senior author of this work.) https://abstracts.asco.org/199/AbstView_199_193232.html
• Measuring circulating tumor DNA in patients before and after treatment was able to help doctors distinguish between true disease progression and pseudoprogression in patients with metastatic melanoma. (Georgina V. Long, MD, PhD, was involved in this work.) https://abstracts.asco.org/199/AbstView_199_191269.html

Multiple Myeloma:

• Patients with active multiple myeloma were found to have a higher proportion of regulatory T cells with high expression of checkpoint receptors, and the addition of checkpoint immunotherapies (either anti-PD-1, anti-LAG3, or anti-TIM3) were able to promote myeloma-specific anti-tumor activity in these cells. https://abstracts.asco.org/199/AbstView_199_190626.html

Ovarian Cancer:

• In a phase II clinical trial, patients whose tumors were highly mutated and expressed higher levels of PD-L1 appeared more likely to respond to pembrolizumab (anti-PD-1 checkpoint immunotherapy). https://abstracts.asco.org/199/AbstView_199_186033.html
• In a phase II clinical trial, vaccination with oregovomab (anti-CA125 antibody immunotherapy) along with chemotherapy was able to enhance anti-tumor immune activity and patient outcomes compared to chemotherapy alone in patients with stage III/IV ovarian cancer. https://abstracts.asco.org/199/AbstView_199_184570.html
• In a phase I clinical trial, mirvetuximab soravtansine (an antibody-drug conjugate immunotherapy that targets the folate receptor alpha) demonstrated increased clinical benefits compared to chemotherapy for patients with platinum-resistant ovarian cancer. https://abstracts.asco.org/199/AbstView_199_190120.html

Pancreatic Cancer:

• In a phase I clinical trial, MVT-5873 (anti-CA19-9 antibody immunotherapy) was able to reduce serum levels of CA19-9 and showed signs of effectiveness in patients with CA19-9+ pancreatic cancer. https://abstracts.asco.org/199/AbstView_199_190708.html
• In a phase I clinical trial, the combination of TG01 (anti-RAS peptide vaccine), GM-CSF (an immunomodulator), and chemotherapy stimulated immune responses in 84% of patients with RAS-mutated pancreatic cancer when the combination was givne after surgery. https://abstracts.asco.org/199/AbstView_199_191964.html

Sarcoma:

• CAR (chimeric antigen receptor) T cells targeting the HER2 receptor appeared safe and led to clinical benefit in several patients with HER2+ sarcoma. https://abstracts.asco.org/199/AbstView_199_194365.html

Stomach & Gastrointestinal Cancer:

• The combination of pembrolizumab (anti-PD-1 checkpoint immunotherapy) and ramucirumab (anti-VEGFR2 antibody immunotherapy) showed promise in patients with gastric adenocarcinoma, both as a first-line treatment and after previous treatment with other therapies. https://abstracts.asco.org/199/AbstView_199_184481.html
• The presence of microsatellite instability (MSI) or high mutational load (>10 mutations / million base pairs) in the tumors of esophagogastric cancer patients were much more likely to benefit from immunotherapy (either anti-PD-1/PD-L1 checkpoint immunotherapy, or combined anti-PD-1/PD-L1 + anti-CTLA-4 checkpoint immunotherapy). https://abstracts.asco.org/199/AbstView_199_191437.html

Come back for more updates from tomorrow's presentations.