CimaVax EGF (EGF-PTI) / In3Bio, CIMAB - LARVOL DELTA

EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=2 | Active, not recruiting | Sponsor: Roswell Park Cancer Institute | Trial primary completion date: Dec 2025 ➔ Jul 2025

Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • RAS

CIMAvax Vaccine, Nivolumab, and Pembrolizumab in Treating Patients With Advanced Non-small Cell Lung Cancer or Squamous Head and Neck Cancer (clinicaltrials.gov) - P1/2 | N=51 | Active, not recruiting | Sponsor: Roswell Park Cancer Institute | Suspended ➔ Active, not recruiting | N=242 ➔ 51 | Trial primary completion date: Dec 2027 ➔ May 2025

Enrollment change • Enrollment closed • Pan tumor • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • ALK • KRAS • PD-L1 • ROS1

CS-01: a next-generation active immunotherapy that depletes epidermal growth factor in squamous NSCLC (AACR-NCI-EORTC 2025) - "EGFR signaling often drives sqNSCLC, yet broad anti-EGFR monoclonal antibodies (mAbs), necitumumab and cetuximab, provide limited benefit and cause substantial toxicity, underscoring the need for better patient selection...In addition to overcoming its CMC limitations, CS-01 surpasses CIMAvax-EGF in both immunogenicity and potency...Our approach offers key advantages over monoclonal antibody therapies, including reduced resistance, fewer doses, and minimal risk of anti‑drug antibodies (ADA). Given the limited accessibility of monoclonal antibodies in many parts of the world, our platform offers a practical, scalable, cost-effective alternative to chronic mAb therapy across oncology, autoimmune, and infectious diseases."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1 • TGFA

EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=2 | Active, not recruiting | Sponsor: Roswell Park Cancer Institute | Suspended ➔ Active, not recruiting | N=42 ➔ 2

Enrollment change • Enrollment closed • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • RAS

A Vaccine (CIMAvax-EGF) for the Prevention of Lung Cancer Development or Recurrence (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Nov 2025 ➔ Nov 2029 | Trial primary completion date: Nov 2025 ➔ Nov 2029

Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Vaccination and personalized cancer vaccines focusing on common cancers in women: A narrative review. (PubMed, Pathol Res Pract) - "Lung cancer studies have discovered interesting outcomes with liposomal vaccines and the potential of CIMAvax-EGF in the prevention of lung cancer. Studies on ovarian cancer highlight personalized cancer vaccines using dendritic cells and various tumor-associated antigens to elicit T-cell responses against cancer cells. Overall, such advancements suggest great promise for future clinical translation of cancer novel immunotherapy-based approaches to effectively counter various types of cancer."

Journal • Review • Brain Cancer • Breast Cancer • CNS Tumor • Colorectal Cancer • Glioblastoma • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer

CIMAvax Vaccine, Nivolumab, and Pembrolizumab in Treating Patients With Advanced Non-small Cell Lung Cancer or Squamous Head and Neck Cancer (clinicaltrials.gov) - P1/2 | N=242 | Suspended | Sponsor: Roswell Park Cancer Institute | Recruiting ➔ Suspended

IO biomarker • Pan tumor • Trial suspension • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • ALK • EGFR • KRAS • PD-1 • PD-L1 • ROS1

EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=42 | Suspended | Sponsor: Roswell Park Cancer Institute | Recruiting ➔ Suspended

Trial suspension • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • RAS

A Vaccine (CIMAvax-EGF) for the Prevention of Lung Cancer Development or Recurrence (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: Nov 2024 ➔ Nov 2025

Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR

Simavax therapeutic vaccine against cancer registered in Belarus (Belteleradiocompany) - "Simavax (CIMAvax-EGF) therapeutic cancer vaccine has been registered in Belarus, BELTA reports citing the Belarusian Ministry of Health....The Ministry of Health emphasized that this is the first and only vaccine registered in Belarus for the treatment of non-small cell lung cancer. The product is indicated for maintenance therapy for patients with advanced non-small cell lung cancer (IIIb/IV) after first-line chemotherapy and with a high concentration of epidermal growth factor in serum."

Approval • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Phase 0 Study of EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer (AACR 2024) - P1 | "Monoclonal antibodies targeting the EGFR (cetuximab, panitumumab) have been in clinical use since 2004 as single agents as well as in combination with chemotherapeutics for patients with metastatic CRC, however primary and secondary resistance is very common...Patients in Cohort A will be treated with mFOLFOX6/Bevacizumab/CIMAvax at present...The standard therapy backbone in Cohort B1 will be FOLFIRI/anti-EGFR therapy, and in Cohort B2 mFOLFOX6/anti-EGFR therapy...This trial is currently open for accrual. Clinicaltrials.gov number NCT06011772"

Combination therapy • IO biomarker • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • EREG

Safety and effectiveness of CIMAvax-EGF administered in community polyclinics. (PubMed, Front Oncol) - "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."

Journal • Lung Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • Squamous Cell Carcinoma • EGFR

CIMAvax Vaccine, Nivolumab, and Pembrolizumab in Treating Patients With Advanced Non-small Cell Lung Cancer or Squamous Head and Neck Cancer (clinicaltrials.gov) - P1/2 | N=242 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Dec 2023 ➔ Dec 2027 | Trial primary completion date: Dec 2023 ➔ Dec 2027

Combination therapy • Metastases • Pan tumor • Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • ALK • KRAS • PD-L1 • ROS1

MONTANIDE™ ISA 51 VG: open access adjuvant dedicated to therapeutic vaccines (SITC 2023) - "It has been proven to be safe and potent thanks to their widely used in clinical trials worldwide for more than thirty years. MONTANIDE adjuvants are also suitable for registration by agencies as MONTANIDE™ ISA 51 VG is used in a licensed vaccine against non-small cell lung cancer, called the CIMAvax-EGF®, registered in eight countries so far."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8

EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Roswell Park Cancer Institute | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS • RAS

A Phase 0 Study of EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Roswell Park Cancer Institute

Combination therapy • Metastases • New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS • RAS

A Vaccine (CIMAvax-EGF) for the Prevention of Lung Cancer Development or Recurrence (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Apr 2024 ➔ Nov 2024 | Trial primary completion date: Apr 2024 ➔ Nov 2024

Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR

Vaccines and monoclonal antibodies in the prolonged treatment of non-small cell lung cancer: 20 years of follow-up (IVC-MG 2023) - "After analyzing more than 3,900 patients in a database integrated with all the clinical trials conducted in the period from 2002 to 2020 with the Cimavax EGF and Vaxira vaccines and the humanized monoclonal antibody nimotuzumab, it was found that around 20% of the patients  had a long survival, greater than 24 months, when they were treated with immunotherapies; but also that a group of patients who were controls in these studies were long survivors. Depending on the product analyzed, predictive parameters of a good response to these treatments were identified, leading to the creation of a therapeutic algorithm to select the appropriate therapy. These parameters are related to the inflammatory level such as the NLR, the PLR and the histological type of the disease."

Immune Modulation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Final results from a phase II trial of CIMAvax-EGF and nivolumab as second-line (2L) therapy after platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). (ASCO 2023) - P1/2 | "Clinical Trial Registration Number: NCT02955290. NSCLC pts who were able to complete the PP combination of C-E plus N at the minimum had numerically better OS compared to historical study cohorts with N as 2L monotherapy. Among pts who completed PP treatment, pts with KRAS wildtype NSCLC had the longest mOS observed. C-E is currently being investigated in combination with pembrolizumab as maintenance therapy after completing 1L chemoimmunotherapy for NSCLC with PD-L1 < 50% and as 1L therapy in combination with pembrolizumab for EGFR/ALK wildtype NSCLC and PD-L1 ≥ 50%."

Clinical • IO biomarker • Metastases • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • KRAS • STK11

Phase 2 trial of epidermal growth factor (EGF) vaccine CIMAvax in combination with pembrolizumab in first line and maintenance setting in advanced non–small cell lung cancer patients. (ASCO 2023) - P1/2 | "A phase 1 trial combining CIMAvax-EGF with nivolumab, an anti-PD1 immune checkpoint inhibitor, showed that the combination is safe and appears to induce higher rate of good anti-EGF antibody response within the first 8 weeks of therapy compared to historical comparison group receiving CIMAvax-EGF alone. Exploratory objectives include characterizing tissue-based immune and EGFR signaling profile as well as serum EGF levels, anti-EGF antibody levels and other blood-based biomarkers in relation to clinical outcomes. Clinical trial information: NCT02955290."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Immune Modulation • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • ROS1

CIMAvax Vaccine, Nivolumab, and Pembrolizumab in Treating Patients With Advanced Non-small Cell Lung Cancer or Squamous Head and Neck Cancer (clinicaltrials.gov) - P1/2 | N=193 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial primary completion date: Jul 2023 ➔ Dec 2023

Combination therapy • Metastases • Pan tumor • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • ALK • PD-L1

Survival of NSCLC Patients Treated with Cimavax-EGF as Switch Maintenance in the Real-World Scenario. (PubMed, J Cancer) - "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."

IO biomarker • Journal • Real-world • Real-world evidence • Dermatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • EGFR

Ongoing Phase II Trial of Anti-PD1 Therapy in Combination with CIMAvax-EGF in Patients with Advanced NSCLC or Squamous Cell Head and Neck Cancer (IASLC-WCLC 2019) - P1/2; " CIMAvax-EGF (2.4 mg IM every 2 weeks x 4 doses, then every 4 weeks thereafter) in combination with Nivolumab (240mg IV every 2 weeks) is being evaluated in this multi-arm phase II study (NCT02955290) as second-line therapy in patients with advanced NSCLC (cohort A), advanced/recurrent head and neck squamous cell cancer (cohort B) and is also being tested as first-line therapy in combination with pembrolizumab (200 mg IV every 4 weeks) in patients with advanced NSCLC with PD-L1 ≥ 50% (cohort C). To date, the combination of CIMAvax-EGF with anti-PD1 therapy has been safe and well tolerated. Enrollment to the phase II portion of this study is ongoing at Roswell Park and is in the process of being expanded to additional U.S. sites."

Clinical • Combination therapy • IO biomarker • P2 data • PD(L)-1 Biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

[VIRTUAL] Evidence for synergistic immune responses in the first-in-human (FIH) combination of B cell-activating immunotherapy (IO) with anti-PD1 immune checkpoint inhibitor nivolumab (N) as 2nd-line therapy in patients (pts) with advanced non-small cell lung cancer (aNSCLC) (AACR-I 2020) - "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."

Checkpoint inhibition • Clinical • IO Biomarker • P1 data • ALK • CD40LG • CD8 • CXCL8 • EGFR • IL15 • IL7 • KRAS • PD-L1

A Vaccine (CIMAvax-EGF) for the Prevention of Lung Cancer Development or Recurrence (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Apr 2023 ➔ Apr 2024 | Trial primary completion date: Apr 2023 ➔ Apr 2024

Trial completion date • Trial primary completion date • Chronic Obstructive Pulmonary Disease • Immunology • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR