CIMAvax-EGF

CimaVax, CIMAvax-EGF, EGF-P64k/Montanide vaccine, "Cuban lung cancer vaccine"

Oncology & imaging

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Note on this profile. CIMAvax-EGF is an approved prescription medicine in Cuba and some other countries for advanced non-small-cell lung cancer, and investigational everywhere else. It is given by injection in an oncology clinic. It is not a research chemical and there is no legitimate route to it outside a prescription or a trial; nothing here describes self-preparation.

Summary

Class: Therapeutic protein-conjugate vaccine, not a short peptide: recombinant human epidermal growth factor (EGF, 53 amino acids) chemically conjugated to the P64k carrier protein from Neisseria meningitidis, adjuvanted with Montanide ISA-51
Mechanism: Immunises the patient against their own EGF so that antibodies mop up circulating EGF and starve EGFR-driven tumours of their growth signal — an antibody-mediated "ligand deprivation" strategy, not a T-cell vaccine
Routes studied: Intramuscular injection, split across four sites; four induction doses two weeks apart, then monthly maintenance indefinitely
Half-life: Not applicable to the vaccine; the relevant measure is anti-EGF antibody titre and the resulting fall in serum EGF, sustained by monthly boosters
Storage: Refrigerated (2–8 °C); an oil-adjuvanted emulsion, must not be frozen
Regulatory status: Registered in Cuba (2008) for advanced NSCLC; registered in several other countries including Peru and Paraguay, with further national authorisations reported since †. Not approved in the US, EU, UK, Australia or South Africa

Doses are as reported in studies or by the community — never recommendations.

1What it is

CIMAvax-EGF came out of the Center of Molecular Immunology in Havana and is the oldest approved therapeutic cancer vaccine of its kind. The idea is unusual and worth stating carefully: most cancer vaccines present a tumour antigen to T cells. CIMAvax instead immunises patients against a normal human growth factor, EGF, which is one of the two main ligands for EGFR. Lung tumours driven by EGFR signalling depend on that ligand; if the patient's own antibodies remove circulating EGF, the receptor is not stimulated.

Because human EGF is a self protein and poorly immunogenic on its own, it is conjugated to a bacterial carrier protein (P64k) and given in a strong oil adjuvant to break tolerance. Strictly, this makes it a protein-conjugate vaccine rather than a peptide vaccine, and the Summary box states that plainly — it is included here because it is routinely grouped with peptide cancer vaccines and is a rare example of one that reached approval.

2How it's thought to work

The P64k carrier provides foreign helper T-cell epitopes, which allows B cells specific for the attached self-EGF to receive help and produce antibodies.

Montanide ISA-51 forms a depot and drives a strong humoral response; monthly boosters are needed to keep titres up.

High-titre anti-EGF antibodies bind circulating EGF, lowering measurable serum EGF concentration.

With less ligand available, EGFR dimerisation and downstream signalling in the tumour fall. Patients with high serum EGF therefore have the most to gain, which is exactly what the trials found.

This is an antibody mechanism. It is mechanistically unrelated to EGFR tyrosine kinase inhibitors, which block the receptor from inside the cell, and unrelated to T-cell vaccines.

A vaccine against the body's own EGF rather than against a tumour antigen. Antibodies raised to the injected EGF mop up circulating EGF so it cannot reach the receptor on lung cancer cells.Schematic — not to scale

3What the research shows

Advanced NSCLC, switch maintenance after first-line chemotherapy

A randomised phase 3 trial in 405 patients with stage IIIB/IV NSCLC who had completed first-line platinum chemotherapy compared CIMAvax-EGF plus best supportive care with best supportive care alone. In the intention-to-treat population the median overall survival difference was modest (roughly 10.8 vs 8.9 months). The benefit was concentrated in patients with high serum EGF concentration (≥870 pg/ml), where median survival was reported as roughly 14.7 vs 8.6 months, and in those who received at least four doses (Rodriguez 2016, Clinical Cancer Research). This is a real randomised result with a plausible predictive biomarker, and it is also a modest absolute effect in a selected subgroup — both halves of that sentence matter. [1]

Graded A/B

Earlier randomised phase 2

A smaller randomised phase 2 reported a survival advantage, most clearly in patients under 60 and in those who achieved a good antibody response (Neninger 2008, J Clin Oncol). Antibody-response-based analyses are landmark-biased and should be read as supporting the mechanism rather than proving benefit. [2]

Serum EGF as a predictive biomarker

Across studies, a fall in serum EGF and a rise in anti-EGF titre tracked together, and high baseline EGF predicted benefit. This is one of the better-developed biomarker stories in therapeutic cancer vaccination, and it is also why the overall population effect is small — most patients are not in the responsive subgroup.

Outside Cuba

A US phase 1/2 programme at Roswell Park has studied CIMAvax-EGF alone and in combination with nivolumab in advanced NSCLC under a US–Cuba research agreement, reporting acceptable safety and encouraging but early signals. A separate line of work is investigating it for lung cancer prevention in high-risk smokers. None of this has produced a registrational result outside Cuba, and the compound is not approved in the US †.

Graded B/C

Other EGFR-pathway cancers

Exploratory work in head and neck, prostate and other EGF-dependent tumours exists in small numbers or preclinical models only.

4Reported side effects and interactions

Literature-reported

the profile is mild by oncology standards and dominated by injection-site and systemic reactogenicity — pain, erythema and induration at the four injection sites, fever, chills, headache, nausea, tremor, and occasionally vomiting in the hours after a dose. Montanide-related nodules can persist. Grade 3–4 events were uncommon in the phase 3, and quality-of-life measures were maintained or improved relative to supportive care alone.

Community-reported

Community use: essentially none documented. Note that "medical tourism" to Cuba for this product is discussed online; that is prescription treatment in another country, not community self-use, and the evidence above is what it rests on.

Theoretical. EGF is required for normal epithelial maintenance and wound healing, so sustained anti-EGF immunity raises a theoretical concern about mucosal repair, skin healing and effects in pregnancy. No major signal has emerged in the treated populations, which are elderly patients with advanced cancer and short follow-up; this is not reassurance for long-term or preventive use in healthy people, and the prevention trials are exactly where it matters.

Interactions. nivolumab (studied in combination); EGFR tyrosine kinase inhibitors act on the same pathway by a different mechanism and the combination is not well characterised; corticosteroids and chemotherapy may blunt antibody responses, which is why vaccination starts after chemotherapy is completed in the approved schedule.

Markers researchers commonly monitor

These come from the approved schedule and the trial protocols:

Marker	Why it's watched
Serum EGF concentration	the central marker. High baseline EGF (≥870 pg/ml in the phase 3 analysis) predicted benefit, and a fall on treatment shows the mechanism is engaged. The most useful single test for this product.
Anti-EGF antibody titre	the direct immunological response; falls between boosters, which is why maintenance dosing is monthly and indefinite.
Overall survival and RECIST imaging	the endpoints that define benefit.
Quality-of-life instruments (EORTC QLQ-C30 or similar)	used as co-primary or key secondary endpoints in the Cuban trials, and relevant because this is palliative-intent maintenance therapy.
CBC, CMP, liver and renal function	routine oncology safety.
Injection-site examination and temperature in the 24 hours after dosing	reactogenicity is expected and the usual reason for symptomatic treatment.
Wound healing and mucosal status if surgery is planned	theoretical, from the EGF mechanism; not an established protocol requirement.

Free for everyone. Safety information is never behind a paywall.

5Formulation and administration context

Supplied as a refrigerated oil-in-water emulsion in vials. Each dose is 2.4 mg of the EGF–P64k conjugate divided into four 0.6 mg injections — classically both deltoids and both gluteal regions — given by clinic staff, with the patient observed afterwards for reactogenicity. Induction is four doses at two-week intervals; maintenance is monthly and continues indefinitely while there is benefit, because antibody titres fall without boosters. Must not be frozen. There is no self-prepared, compounded or version, and no dose calculation appropriate to publish.

6Commonly studied alongside

Platinum-based first-line chemotherapy (completed before vaccination in the approved schedule); nivolumab; Montanide ISA-51 as adjuvant. Conceptually related: the other therapeutic cancer vaccines in this tier, particularly Nelipepimut-S (profile 232) and IMA901 (profile 236), which did not reach approval.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved. Investigational, studied under an institutional US–Cuba research collaboration †
European Union	Not authorised by the EMA. National authorisations in one or more non-EU European countries have been reported †
United Kingdom	Not licensed
Australia	Not approved by the TGA
South Africa	Not registered with SAHPRA
Cuba and other countries	Registered in Cuba since 2008 for advanced NSCLC; registered in several other countries including Peru and Paraguay. The full current list is not reliably documented in English-language sources †
Sport	Not listed by WADA; no performance application

8Open questions

Does the high-serum-EGF subgroup benefit replicate in a non-Cuban population and against a modern standard of care that includes checkpoint inhibitors?
Is long-term anti-EGF immunity safe in people who are not in the last years of life — the central question for the lung-cancer-prevention programme?
How does ligand deprivation interact with EGFR tyrosine kinase inhibitors and with immune checkpoint blockade?

9References

1Rodriguez PC et al. (2016). 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. PubMed · DOI
2Neninger Vinageras E et al. (2008). Phase II randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer. Journal of Clinical Oncology. PubMed
3Garcia B et al. (2008). Effective inhibition of the epidermal growth factor/epidermal growth factor receptor binding by anti-epidermal growth factor antibodies is related to better survival in advanced NSCLC patients treated with the EGF cancer vaccine. Clinical Cancer Research. PubMed · DOI
4Saavedra D, Crombet T (2017). CIMAvax-EGF: a new therapeutic vaccine for advanced non-small cell lung cancer patients. Frontiers in Immunology. PubMed · DOI
5Roswell Park Comprehensive Cancer Center (ongoing). Phase 1/2 studies of CIMAvax-EGF with and without nivolumab in advanced NSCLC — trial records [verify status]. PubMed
6ClinicalTrials.gov. CIMAvax-EGF trial records (US programme). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

31 Oct 2026Profile published — awaiting medical review

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