2016 AACR Annual Meeting Report

In line with the Society for Immunotherapy of Cancer's (SITC) decades-old mission to advance cancer immunotherapy, we continue to monitor all news related to the field for our members. As such, we are pleased to recap highlights from the 2016 Annual Meeting for the American Association for Cancer Research (AACR), held in New Orleans, Louisiana on April 16 – 20. Topics in cancer immunotherapy were prevalent at the 2016 meeting, with subject matter including genomics-guided immunotherapy, immunotherapy combinations, small-molecule approaches to immunotherapy, mechanisms of resistance and lack of response in cancer immunotherapy, and therapies targeting immune checkpoints.

As evidence of the rapid advances in research, Vice President Biden called out immunotherapy as “…an important part of America’s anti-cancer strategy” during his address to the cancer research community on Wednesday. The presidentially-appointed champion of the National Cancer Moonshot Initiative went on to identify opportunities toward the goal of accelerating progress in the pursuit of a cure for cancer, including increased interdisciplinary collaboration and open access scientific publications.

While the conference was replete with exciting news for the field of cancer immunotherapy, including poster sessions and other educational sessions, below are some notable developments from the clinical trials plenary sessions employing immunotherapeutic strategies:

Nivolumab immunotherapy increases survival in patients with head and neck cancer

The CheckMate-141 randomized phase III study investigating nivolumab (anti-PD-1) immunotherapy versus the investigator’s choice of either methotrexate, docetaxel, or cetuximab represents the first treatment approach for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) to increase survival in a phase III trial in over a decade. Presented by Dr. Maura Gillison from The Ohio State University in Columbus, Ohio, this clinical trial enrolled 361 patients with HNSCC who were refractory to disease within six months of platinum-based chemotherapy. Strikingly, the risk of death in nivolumab-treated patients was reduced by 30 percent and the one-year overall survival rate was doubled. Due to this increased benefit, the primary endpoint of the study was determined to have been met earlier than the scheduled date of completion, which allowed patients in the control arm of the trial to cross over and receive nivolumab. Corresponding author and SITC at-large director, Dr. Robert Ferris from the University of Pittsburgh Cancer Institute in Pittsburgh, Pennsylvania, shared his insights about the study after the presentation in this interview.

Lasting responses to pembrolizumab first-line therapy observed in Merkel cell carcinoma

SITC member Dr. Paul Nghiem from the Fred Hutchinson Cancer Research Center at the University of Washington in Seattle, Washington presented data from an open-label phase II trial seeking to evaluate pembrolizumab (anti-PD-1) as a frontline therapy for advanced Merkel cell carcinoma. An objective response rate was documented in 14 of the 25 patients (56 percent) for whom radiologic assessments have been evaluated thus far, and responses to this immunotherapy continue in 12 of those patients (86 percent) with a median progression-free survival approaching three times that of traditional chemotherapy. PD-L1 expression in the tumor was not found to correlate with a therapeutic response. An ongoing area of investigation includes the mechanism(s) of the anti-tumor response in the presence and absence of the Merkel cell polyomavirus.

OX40 agonist dose escalation study well-tolerated in patients with refractory solid tumors

The safety and pharmacokinetics of the OX40 T-cell costimulatory agonist, MOXR0916, were evaluated in a first-in-human phase I open-label study presented by Dr. Aaron Hansen from the Princess Margaret Cancer Centre in Toronto, Ontario. A heterogeneous population of patients with solid tumors refractory to standard treatment were enrolled to determine both the dose and pharmacokinetics of this immunotherapy. Early reports of this ongoing trial indicate that MOXR0916 was well-tolerated with no dose-limiting toxicities or serious adverse events and demonstrate evidence of stable disease in a subset of patients. These findings support ongoing efforts to evaluate further the potential of MOXR0916 in specific types of cancer, both as a monotherapy and in combination with anti-PD-L1.

Systemic immune stimulation upon PEG-IL-10 treatment of advanced solid tumors

A phase I study to establish the safety and anti-tumor activity of PEGylated human IL-10 (AM0010) was reported by Dr. Jeffrey Infante from the Sarah Cannon Research Institute in Nashville, Tennesee. AM0010, which has been shown to eliminate tumors and stimulate the expansion of tumor-specific memory CD8+ T cells in preclinical models, was administered to 33 patients with advanced solid cancers. The immune response to this well-tolerated monotherapy included a decrease in peripheral regulatory T cells and an increased population of activated CD8+ T cells both in the blood and at the site of the tumor. Objective responses and prolonged stable disease of six or more months were observed in subsets of patients as a result of this systemic immune stimulation.

In Case You Missed It—SITC's Mid-conference Report from AACR Sent April 20, 2016

Combination therapy with nivolumab/ipilumamab illustrates improved survival in advanced melanoma

The latest results of the phase II CheckMate-069 trial evaluating the efficacy of combination immune checkpoint blockade in patients with advanced melanoma were released. Highlights of this study, presented by SITC member Dr. Michael Postow of Memorial Sloan Kettering Cancer Center, include a two-year overall survival of 64 percent in the total study population treated with the combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) versus 54 percent for those treated with ipilimumab alone. For BRAF wild-type patients, two-year overall survival was 69 percent with the combination immunotherapy compared with 53 percent for the ipilimumab monotherapy. Notably, the median overall survival has not yet been reached among patients receiving combination therapy. Learn more by watching the video interview produced by OncLive.

First of its kind CD4+ T cell immunotherapy offers evidence of efficacy in metastatic malignancies

SITC member Dr. Yong-Chen Lu from the National Cancer Institute of the National Institutes of Health, reported on a novel phase I clinical trial utilizing genetically-engineered CD4+ T cell immunotherapy for the treatment of metastatic solid cancers. This study, in which HLA-DPB1*0401-restricted T cells specific for the MAGE-A3 antigen (present in up to 33 percent of tumor specimens) were adoptively transferred into patients, has yielded ongoing objective partial responses in three out of 14 patients with a variety of metastatic cancer types, and has laid the foundation for a phase II study that is now underway. Watch the OncLive video interview to learn more about this phase I trial.

Five-year survival follow-up of patients who received anti-PD-1 immunotherapy for advanced melanoma

The most extensive follow-up on long-term overall survival following nivolumab monotherapy in previously treated patients with advanced melanoma was presented by SITC Secretary/Treasurer Dr. Stephen Hodi of Dana-Farber Cancer Institute. The robustness of this well-tolerated immunotherapeutic intervention is underscored by the 34 percent overall survival observed with no new deaths or safety signals five years after discontinuing treatment. Watch the video for more information.

PD-L1 expression levels in advanced melanoma correlate with pembrolizumab monotherapeutic outcomes

In a follow-up to KEYNOTE-006, a phase III trial that demonstrated superior outcomes following treatment with pembrolizumab (anti-PD-1) compared with ipilimumab as a first-line therapy for advanced melanoma, Dr. Matteo Carlino discussed recent data focused on expression of the T cell inhibitor PD-L1 on tumor and surrounding immune cells. This study revealed a correlation between the number of cells expressing PD-L1 and improvement in survival when treated with pembrolizumab compared with those treated with ipilimumab alone. However, a therapeutic benefit was also observed in PD-L1-negative patients who received pembrolizumab.

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