CimaVax EGF (EGF-PTI)

We conclude that community polyclinics constitute the optimal scenario for administering those cancer vaccines that are safe and require prolonged maintenance in patients with advanced cancer, despite the continuous deterioration of their general condition. https://rpcec.sld.cu/trials/RPCEC00000205-En, identifier RPCEC00000205.

P1/2, N=242, Recruiting, Roswell Park Cancer Institute | Trial completion date: Dec 2023 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2027

P1, N=42, Recruiting, Roswell Park Cancer Institute | Not yet recruiting --> Recruiting

P1, N=42, Not yet recruiting, Roswell Park Cancer Institute

P1, N=60, Recruiting, Roswell Park Cancer Institute | Trial completion date: Apr 2024 --> Nov 2024 | Trial primary completion date: Apr 2024 --> Nov 2024

P1/2, N=193, Recruiting, Roswell Park Cancer Institute | Trial primary completion date: Jul 2023 --> Dec 2023

The most frequent adverse events were pain (27.3%) or induration (7.3%) at the injection site and local erythema (10.9%). CIMAvax-EGF, as an EGF depleting immunotherapy used as switch-maintenance was safe and effective in patients with NSCLC.

P1, N=60, Recruiting, Roswell Park Cancer Institute | Trial completion date: Apr 2023 --> Apr 2024 | Trial primary completion date: Apr 2023 --> Apr 2024

P1/2, N=193, Recruiting, Roswell Park Cancer Institute | Trial primary completion date: Dec 2022 --> Jul 2023

Humoral response to CIMAvax-EGF was achieved earlier and in a greater number of patients with the combination compared to historical control. Four out of 12 evaluable patients had an objective response.

Background Previous studies have shown that baseline concentrations of EGF in serum could be considered a biomarker of the efficacy of the therapeutic vaccine CIMAVax-EGF...Conclusions The results showed that patients with high baseline serum EGF concentrations and poor prognosis, achieve comparable survival to those with low baseline serum EGF concentrationsa and better prognosis of the disease in terms of survival. Patients who received at least 4 doses of treatment, achieved response to first-line onco-specific treatment, and had ECOG between 1 and 2, received the greatest benefit.

P1/2, N=23, Completed, Instituto Oncológico Dr Rosell | Active, not recruiting --> Completed | Trial completion date: Jun 2021 --> Dec 2021

P1, N=60, Recruiting, Roswell Park Cancer Institute | Trial primary completion date: Mar 2022 --> Apr 2023

P1/2, N=193, Recruiting, Roswell Park Cancer Institute | Active, not recruiting --> Recruiting | N=42 --> 193 | Trial completion date: Jun 2023 --> Dec 2023 | Trial primary completion date: Jun 2022 --> Dec 2022

Moreover, the median overall survival of patients treated with CIMAvax-EGF was 16.09 months. In conclusion, our results suggest that the immunorestoration generated by the administration of BT after first-line chemotherapy may induce a better immune response to CIMAvax-EGF that could translate into the clinical benefit of patients diagnosed with advanced NSCLC.

P1/2, N=42, Active, not recruiting, Roswell Park Cancer Institute | Suspended --> Active, not recruiting | N=181 --> 42

P1/2, N=181, Suspended, Roswell Park Cancer Institute | Recruiting --> Suspended

Conclusion The combination of an anti–EGF vaccine with afatinib is well tolerated and induces a sustained immunogenic effect. Vaccination against EGF might enhance the clinical efficacy of EGFR TKIs.

This manuscript reviews the state-of-the-art NSCLC therapy and proposes the most promising scenarios for evaluating CIMAvax-EGF, particularly in combination with TKIs or ICIs. We hypothesize that the optimal combination of CIMAvax-EGF with established therapies can further contribute to transform advanced cancer into a manageable chronic disease, compatible with years of good quality of life.

P1, N=60, Not yet recruiting, Roswell Park Cancer Institute | Trial completion date: Aug 2022 --> Jul 2023 | Trial primary completion date: Aug 2021 --> Jul 2022

We found that EGF and tumor growth factor alpha (TGFα) significantly decreased the antiproliferative activity of the RET inhibitor BLU-667 in CCDC6-RET cells and brigatinib, alectinib and crizotinib in EML4-ALK translocated cells. In conclusion, anti-EGF VacAbs significantly increased the antitumor activity of TKIs in ALK and RET-positive cell lines. Clinical trials of an EGF vaccine in combination with ALK and RET TKIs are warranted.

In conclusion, the CIMAvax-EGF vaccine induces an EGF-specific protective humoral response in a high percent of NSCLC vaccinated patients, the quantity and quality of which were associated with clinical benefit (clinical trial registration number: RPCEC00000161, http://registroclinico.sld.cu/). EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; Ab: antibody; AR: amphiregulin; NSCLC: non-small-cell lung cancer; rhEGF: recombinant human epidermal growth factor; BSC: best supportive care; TGFα: tumor growth factor alpha; IL-8: interleukin 8; MAb: monoclonal antibody; SPR: surface plasmon resonance.

Peripheral blood parameters and immunosenescence biomarkers together with basal EGF concentration in serum resulted in good predictors of the CIMAvax-EGF success in advanced NSCLC. Future research should explore molecular and genetic profile as biomarkers for CIMAvax-EGF and it combination with immune-checkpoint inhibitors. The study illustrates the application of a new methodology, based on causal inference, to evaluate multivariate pre-treatment predictors. The multivariate approach allows realistic predictions of the clinical benefit of patients and should be introduced in daily clinical practice.

Background: We have recently shown that antibodies generated by vaccination (anti-EGF VacAbs) potentiate the effects of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor mutant (EGFR-mut) cell lines (1) and a Phase I/II clinical trial of an anti-EGF vaccine in combination with afatinib has been initiated...In combination, the anti-EGF VacAbs significantly enhanced the antitumor activity of BLU667 in LC-2/ad, trametinib and encorafenib in HT29, trametinib in DLD1 and LS174T and trametinib, taselisib, alpelisib and copanlisib in H508 cells... Anti-EGF VacAbs potentiate the antitumor effects of RET, MEK, BRAF and PI3K inhibitors in tumor cell lines. Our data provide a rationale for clinical trials testing the combination of anti-EGF VacAbs with kinase inhibitors in RET-translocated, KRAS, BRAF and PIK3CA mutant NSCLC and CRC patients.

To assess this, we conducted the FIH trial combining B cell-activating IO (CIMAvax-EGF (C)) with T cell-activating IO (PD-1 blockade with nivolumab (N)). This study provides evidence for synergistic effects of combining B and T cell activating IO in aNSCLC pts. C+N generated higher anti-EGF titers in more pts at an earlier time point vs. C alone, which is the first demonstration in pts of enhancement of Ab responses by immune checkpoint blockade.

P1/2, N=181, Recruiting, Roswell Park Cancer Institute | Trial completion date: Jun 2022 --> Jun 2023

P1/2, N=181, Recruiting, Roswell Park Cancer Institute | Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Jun 2020 --> Jun 2022

P1, N=60, Not yet recruiting, Roswell Park Cancer Institute