Experimental Treatments for Lung Cancer

A wide range of experimental treatments for lung cancer are being developed, many of which are in ongoing clinical trials.

Below is a list, by category, of some of these potential therapies, with a reminder that drugs in clinical trial may never be approved for patient use.

Targeted therapies

Targeted therapies differ from chemotherapy in that the therapy does not act indiscriminately on healthy and cancerous cells alike. Targeted therapies are often antibodies or proteins that have been specifically designed to identify and interact with a precise target. The target is generally involved in processes that affect cell growth or cell death, or are known to act abnormally in cancer. Examples of targeted therapies currently in Phase 3 clinical trials are:

Vargatef (nintedanib), in combination with Taxotere (docetaxel) or placebo plus docetaxel, which displayed positive results in an ongoing Phase 3 clinical trial (NCT00805194). Results to date were published in the medical journal The Lancet Oncology, and the combination showed an increase in progression-free survival compared with placebo (3.4 versus 2.7 months) and increased overall survival compared to the placebo (10.9 versus 7.9 months).
Abemaciclib (LY2835219), being developed by Lilly Oncology, inhibits the kinase activity of two proteins CDK4 and CDK6, blocking cell division and therefore tumor growth. It is currently in Phase 3 clinical trial (NCT02152631).
ABP 215 (biosimilar bevacizumab), developed by Amgen and Allergan, has recently completed a Phase 3 clinical trial (NCT01966003) comparing it to bevacizumab. Results showed that ABP 215, an antibody targeting vascular endothelial growth factor A (VEGF-A), was similar in clinical outcomes — primarily, measures of overall response — to the original drug.
Aldoxorubicin, developed by CytRx, is in Phase 2 clinical trial (NCT02200757) for the treatment of small-cell lung cancer (SCLC).
Xgeva (denosumab), developed by Amgen, is in a Phase 3 clinical trial (NCT02129699) to treat bone metastases in non-small cell lung cancer (NSCLC).

This is only a selection of the many targeted therapies currently being developed. Other therapies include acalabrutinib (ACP-196, NCT02448303), ado-trastuzumab emtansine (NCT02675829), alisertib (NCT02038647), CC-486 (NCT02250326), VAL-083 (clinical trials planned) and tesevatinib (NCT02616393).

Tyrosine kinase inhibitors

Tyrosine kinase inhibitors (TKIs) are a common targeted therapy for lung cancer, as the tyrosine kinase HER-1 (or EGFR) is frequently misregulated in cancers. Inhibiting this, and other tyrosine kinases, can stop tumor growth. Examples of TKI inhibitor therapies are:

Dacomitinib, developed by Pfizer, which is a ‘pan-HER’ inhibitor. It is showing positive results in the on-going Phase 3 open-label study, ARCHER-1050 (NCT01774721).
AP32788, developed by Ariad, targets both HER-1 and HER-2. After showing positive results in preclinical trials, it has entered a Phase 1/2 clinical trial (NCT02716116).

Antagonists

In terms of therapy, an antagonist is a substance that blocks the action of another substance by competing for a specific target.

LY2510924, developed by Lilly Oncology, blocks the activation of CXCR4 (a receptor that is important for tumor growth and metastasis). It has completed a Phase 2 clinical trial to treat SCLC, showing acceptable toxicity but not improved efficacy.

Immune system checkpoint inhibitors

Immune system checkpoint inhibitors aim to treat tumors by helping the immune system identify and target cancer cells for destruction. Cancer cells often use the body’s own safety measures to hide from the immune system. Immune system checkpoint inhibitors remove that evasion checkpoint, allowing the body’s immune system to kill the cancer by itself. The following are examples currently in clinical trials:

Bavencio (avelumab), developed by Pfizer and Merck KGaA, which has shown positive results in previous clinical trials. A Phase 3 trial (NCT02576574) as a first-line treatment for NSCLC is ongoing.
Imfinzi (durvalumab), developed by AstraZeneca, is currently in a Phase 3 clinical trial (NCT02125461). It has produced a significant improvement in progression-free survival compared to placebo in patients with NSCLC.
Yervoy (ipilimumab), developed by Bristol-Myers Squibb, is in a Phase 3 clinical trial (NCT02477826) in combination with Opdivo (nivolumab) for the treatment of NSCLC. It also shown positive results in combination with Opdivo for the treatment of SCLC in Phase 1/2 trials.
Tremelimumab (CP-675,206), developed by AstraZeneca, is in a Phase 3 clinical trial in combination with Imfinzi (durvalumab) to treat NSCLC (NCT02352948) and SCLC (NCT03043872).
Bavituximab, developed by Peregrine Pharmaceuticals, has received fast-track designation from the U.S. Food and Drug Administration (FDA) as a second-line treatment of NSCLC.

Cancer vaccine

Cancer vaccines aim to give the immune system a boost to target lung cancer cells. There are no currently approved cancer vaccines in the U.S., but many are currently in clinical trials. For example, CimaVax, developed by Roswell Park Cancer Institute, is in a Phase 1/2 clinical trials in the U.S. (NCT02955290) and has already shown positive results in Phase 3 and 4 clinical trials outside the U.S. Other experimental treatments include: TG4010 (NCT02823990), CD40LGVAX, Tecemotide (L-BLP25) and EGF Vaccine (NCT02187367).

Other information

Drugs that make it to Phase 3 clinical trials may not progress further, or they may be tested to treat other cancers. One example is Ganetespib, which is a heat shock protein 90 (HSP90) inhibitor, developed for the treatment of ALK-positive NSCLC. It proceeded to Phase 3 clinical trials (NCT01798485, GALAXY-2), but showed no significant effect and its future is uncertain. Other examples include Selumetinib, Custirsen and the MAGE-A3 cancer vaccine.

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