Introduction: Immunotherapy Research Milestones

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Moderator Louis M. Weiner, MD, introduces a panel discussion focused on monoclonal antibody-based immunotherapy for patients with various types of cancer. The expert panel includes Robert Dreicer, MD, Omid Hamid, MD, Roy S. Herbst, MD, PhD, and Mark A. Socinski, MD, with additional commentary from Brian I. Rini, MD, and Nicholas J. Vogelzang, MD.

The historical evolution of cancer research has included many breakthrough discoveries, notes Weiner. In recent years, immune-based therapies for cancer have shown the potential for long-term durable remissions, and even the possibility of cures in select cancer indications.

Immunotherapy research milestones:

• 1976: Interleukin-2 (IL-2) discovered
• 1985: IL-2 demonstrated to be an effective cancer immunotherapy
• 1992: High-dose IL-2 approved for metastatic kidney cancer
• 1997: First monoclonal antibody, rituximab, approved as a treatment for B-cell malignancies
• 1998: IL-2 approved for the treatment of metastatic melanoma
• 2010: Sipuleucel-T, the first dendritic cell vaccine, approved for the treatment of metastatic castrate-resistant prostate cancer
• 2011: Ipilimumab was approved for the treatment of melanoma

These milestones opened the door for PD-1 and PD-L1 inhibiting agents, which have generated excitement in recent years. These therapies are the focus of significant clinical development, with several ongoing clinical trials for multiple cancer indications, notes Weiner.

PD-1 inhibitors in development:

• Nivolumab (fully human IgG4 monoclonal antibody)
• Pembrolizumab (MK-3475; humanized IgG4 monoclonal antibody)
• Pidilizumab (humanized IgG1 monoclonal antibody)
• AMP-224 (B7-DC/lgG1 fusion protein)

Anti-PD-L1 therapies in development:

• MPDL3280A (engineered human antibody)
• MEDI4736 (fully human IgG1 monoclonal antibody)