Early-phase clinical trials open new opportunities

Rachel E. Sanborn, M.D.

Rachel E. Sanborn, M.D.
Co-medical director, Providence Thoracic Oncology Program
Providence Cancer Center

Published December 2012

The rapid pace of development of mutation-targeted anti-cancer agents, and recent breakthroughs in immune-based cancer therapy, have led to an unprecedented era of cancer research and discovery.

Clinical trials have begun to focus more on smaller studies, with some agents approved for use based upon significant results from early-phase clinical research. Oncology researchers at Providence Cancer Center are focused on expanding opportunities for patients with all types of cancer to participate in clinical trials, including exciting early-phase studies. 

Providence Cancer Center recently partnered with Bristol-Myers Squibb and nine other institutions to form the International Immuno-Oncology Network. Through collaboration, the network seeks to advance science and therapy by better understanding the immune system’s interactions with cancer.

Other participating institutions include the Dana-Farber Cancer Institute, Johns Hopkins, Memorial Sloan-Kettering Cancer Center, the University of Chicago, the Institut Gustave Roussy in France, and the Royal Marsden NHS Foundation in the United Kingdom, among others.

The partnership’s first trial is a phase I study of the combination of anti-PD-1 (BMS-936558) and anti-KIR (BMS-986015). The anti-PD-1 agent recently demonstrated exciting response rates and antitumor activity in heavily pretreated patients with advanced solid cancers and with a relatively low toxicity profile. The phase I study is evaluating whether antitumor activity is improved with this combination of agents compared to anti-PD-1 alone.

Anti-PD-1 is a monoclonal antibody that binds to the programmed cell death 1 (PD-1) receptor. The receptor plays a role in T cell tolerance, and its activation helps cancers evade recognition by the host immune system. Blockade of PD-1, an inhibitory receptor expressed by T cells, can overcome immune resistance. Likewise, KIR (killer cell Ig-like receptors) receptors play a role in suppressing activation of natural killer cells. Inhibition of KIR receptors with targeted antibodies may enhance antitumor activity.

Patients with previously treated advanced solid tumors are eligible to participate in the study’s initial dose-escalation phase. This will be followed by a cohort expansion phase, with cohorts enrolling patients with non-small cell lung cancer, melanoma, and renal cell, colorectal and ovarian carcinomas.

Other currently available immunotherapy studies for patients with advanced cancers include a trial investigating anti-CD137. This agonistic antibody is designed to activate CD137, potentially up-regulating multiple immune pathways to increase host recognition of cancer.

Tumor-specific studies of anti-PD-1 are also currently enrolling patients with hepatocellular carcinoma and melanoma. For patients with melanoma, a study evaluating the combination of recombinant IL-21 with ipilimumab is ongoing.

Developed at Providence’s Earle A. Chiles Research Institute, the anti-OX-40 agent is under investigation in combination with cyclophosphamide and radiation for patients with advanced prostate cancer. The anti-OX-40 agent is an agonistic antibody that enhanced T cell proliferation, particularly in patients with prostate cancer, in the first-in-human phase I trial. The current study is investigating the immune effects of the combination with the potentially complementary immune-activating cyclophosphamide and radiation.

A study combining anti-OX-40 and stereotactic radiation of metastases is also under way in patients with breast cancer.

Early-phase studies involving targeted agents include an ongoing dose-escalation trial of the novel agent carboxyamidotriazole orotate for patients with advanced cancers. For patients with advanced non-small cell lung cancer, an early study investigating the combination of carboplatin, pemetrexed, bevacizumab and the targeted MTOR inhibitor everolimus soon will be available. This study is part of a new research consortium, Cancer Research and Biostatistics Clinical Trials Consortium, in which Providence Cancer Center is a partner.

Broader understanding of the immune system and the genetic drivers of malignancy has opened exciting doors in cancer investigation and therapy. Advances in care depend on clinical trials and research, and on patient and physician participation. The team at Providence is happy to answer inquiries about current clinical trials.

To learn more about early-phase studies at Providence Cancer Center, contact Scot Lary, RN, at 503-215-2604.

Clinical articles by Rachel E. Sanborn, M.D.