One of the most exciting recent developments in cancer immunotherapy is the discovery that patients with lung cancer sometimes respond remarkably well to treatment with checkpoint inhibitors. These are drugs that “release the brakes” on immune cells, empowering the immune system to mount a stronger attack against cancer. One checkpoint inhibitor, nivolumab (trade name Opdivo®, made by Bristol Myers-Squibb) is already FDA approved for the treatment of a type of lung cancer called ‘squamous’ non-small cell lung cancer (NSCLC) that has recurred after prior chemotherapy. And last month, at the American Society of Clinical Oncology (ASCO) annual meeting, we learned that nivolumab was more effective than chemotherapy at treating recurrent ‘non-squamous’ NSCLC. Now, two new clinical trials will test a combination of immune checkpoint inhibitors as first-line treatment for NSCLC lung cancer in patients who have had no prior chemotherapy.
The first is a phase III trial of a checkpoint inhibitor called durvalumab (MEDI4736, made by AstraZeneca/MedImmune) with or without tremelimumab, another checkpoint inhibitor (also made by AstraZeneca/MedImmune), versus standard of care chemotherapy for NSCLC. The trial will open to patient accrual this month—July 2015. Durvalumab (MEDI4736) is a PD-L1-blocking antibody that prevents cancer from engaging the PD-1 “brake” on immune cells, thereby robbing cancer of an important defense. Tremelimumab blocks a molecule on T cells called CTLA-4. By targeting two separate checkpoints simultaneously, the hope is that these drugs will complement each other, leading to more powerful results. The principal investigator for the trial is Naiyer Rizvi, M.D., of Columbia University School of Medicine, who is the expert reviewer for CRI’s lung cancer immunotherapy page.
The second trial is a phase III trial of nivolumab with or without ipilimumab versus standard of care chemotherapy in NSCLC, which opens in August of this year. Nivolumab is a checkpoint inhibitor that blocks the PD-1 checkpoint on immune cells. Ipilimumab (trade name Yervoy®, made by Bristol Myers-Squibb) blocks CTLA-4.
Both these trials will attempt to answer an important question: whether combination immunotherapy treatments can provide better therapeutic results than the current standard of care for lung cancer, which is conventional chemotherapy. Early phase trials have suggested that the combination of PD-1 and CTLA-4 checkpoint inhibitors can provide better therapeutic responses than either drug alone. The new phase III trials will test this combination in a head-to-head comparison with the standard of care therapies for lung cancer.
If proved more effective than the standard of care, this immunotherapy combo would be a radical departure from the conventional treatment of lung cancer with chemotherapy. And since chemotherapy comes with significant toxicity and is rarely curative, this change will likely be welcomed by patients.
Because it treats the immune system, not the tumor, immunotherapy holds out the promise of long-term, durable responses—perhaps even cures—for many types of cancer, including lung. Lung cancer is the leading cause of cancer mortality globally, representing nearly 1 in 5 cancer-related deaths.