is a therapeutic not preventive NSCLC (non-small cell lung cancer) immunotherapy. It doesn’t prevent cancer but rather has the potential to convert it into a more chronic disease. To put this in perspective, NSCLC accounts for ~85% of all lung cancer, which is the leading cause of worldwide cancer mortality ( ).
A therapeutic vaccine for NSCLC, CimaVax-EGF consists of recombinant human Epidermal Growth Factor (EGF) chemically conjugated to recombinant carrier protein P64 from Neisseria meningitidis. This conjugate is adjuvanted with the adjuvant Montanide ISA 51 to help drive strong immune responses.
Data on CimaVax-EGF
Formulated and tested by scientists at Cuba’s Havana-based Center of Molecular Immunology, pilot clinical trials since 1998 helped them steadily refine the product (see table below from).
- The 1st pilot study (1995-1996) with 10 patients helped select the carrier protein P64 from Neisseria meningitidis.
- The 2nd (1997-1999) and 3rd (1998-2001) pilot studies with 20 patients helped select
- Montanide ISA 51 as the adjuvant.
- Cyclophosphamide pre-Rx as an immunomodulating agent.
- Helped identify Good (GAR) and Poor (PAR) Antibody Responders, by measuring anti-EGF antibody.
- The 4th pilot study (2000-2003) with 43 patients helped distinguish clinical outcome between
- GAR and PAR, with the former associated with longer survival times.
- Low and high serum EGF concentrations, respectively, were associated with GAR and PAR. High serum EGF concentrations are linked to poor NSCLC prognosis, suggesting CimaVax could trigger an effective anti-EGF immune response.
- The 5th pilot study (2001-2005) showed
- High dose vaccine could be safely combined with chemotherapy.
- Increased anti-EGF antibody concentrations.
- Increased survival times and even achieved remission in 2 out of 20 patients.
As of 2016, >3000 advanced NSCLC patients have received the CimaVax-EGF vaccine and shown that it is safe, immunogenic and modestly effective (3,).
Potential Usefulness Of CimaVax-EGF
Even though overall survival benefit with CimaVax is modest, ~2X, reason it finds a place among lung cancer Rx is available options are limited. Only ~17% of lung cancer patients survive >5 years post-diagnosis with standard chemotherapy () and proportion is only ~4% for those with metastasis.
- Overall lung cancer survival rates have improved only in the small subset of patients with specific mutations in the EGF receptor or with ALK translocations. Targeted molecular therapies such as , , can extend their median survival from ~5 to 6 months to ~9 to 11 months, i.e., ~2X (6). Unfortunately, patients with such mutations constitute only 15 to 20% of NSCLC patients (7).
- OTOH, CimaVax seeks to disrupt the interaction of EGF with its receptor, EGFR, which is over-expressed on ~40 to 80% of NSCLC (
). EGFR over-expression is linked to poor prognosis, reduces survival chances and predisposes to resistance to therapy (9). Potential for lengthening overall survival time in a much larger group of lung cancer patients with an immunotherapy that’s now proven to be safe, that’s the unique benefit of CimaVax.
- It increased overall survival from ~8 months with chemotherapy alone to ~13 months.
- In patients younger than 60 years old, CimaVax increased survival time from ~5 months to ~12 months ( ).
- Based on such data CimaVax is approved as 2nd line Rx for NSCLC in Cuba, Peru and Venezuela (11). Ongoing Phase III clinical trials seek to expand its regulatory approval in other countries including the US.
1. Molina, Julian R., et al. “Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship.” Mayo Clinic Proceedings. Vol. 83. No. 5. Elsevier, 2008.
2. Rodríguez, Pedro C., et al. “Clinical development and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer therapy.” MEDICC Rev 12.1 (2010): 17-23.
3. Saavedra, Danay, et al. “Biomarkers related to immunosenescence: relationships with therapy and survival in lung cancer patients.” Cancer Immunology, Immunotherapy 65.1 (2016): 37-45.
4. Rodriguez, Pedro C., et al. “A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small-Cell Lung Cancer Patients.” Clinical Cancer Research (2016): clincanres-0855.
5. National Institutes of Health. Cancer of the Lung and Bronchus – SEER Stat Fact Sheet
6. Camidge, D. Ross, William Pao, and Lecia V. Sequist. “Acquired resistance to TKIs in solid tumours: learning from lung cancer.” Nature reviews Clinical oncology 11.8 (2014): 473-481.
7. Karachaliou, Niki, et al. “Systemic treatment in EGFR-ALK NSCLC patients: second line therapy and beyond.” Expert review of anticancer therapy 14.7 (2014): 807-815.
8. Toyooka, Shinichi, et al. “Molecular oncology of lung cancer.” General thoracic and cardiovascular surgery 59.8 (2011): 527-537.
9. Hirsch, Fred R., et al. “Epidermal growth factor receptor in non–small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis.” Journal of Clinical Oncology 21.20 (2003): 3798-3807.
10. Vinageras, Elia Neninger, et al. “Phase II randomized controlled trial of an epidermal growth factor vaccine in advanced non–small-cell lung cancer.” Journal of Clinical Oncology 26.9 (2008): 1452-1458.
11. Domingues, Duarte, et al. “Immunotherapy and lung cancer: current developments and novel targeted therapies.” Immunotherapy 6.11 (2014): 1221-1235.