NY-ESO-1 Iscomatrix / Ludwig Institute for Cancer Research, CSL Behring - LARVOL DELTA

An innovative Dendritic Cell Vaccine for Castration-Resistant Prostate Cancer Patients: radiological PFS results (ESMO 2017) - P2a; "...Clinical evidence supports a beneficial effect of immune stimulation in CRPC patients shown by sipuleucel-T...Patients received DC vaccination loaded with the tumor-associated antigens MUC1, NY-ESO-1, and MAGE-C2...Innovative DC vaccination is feasible and safe in early CRPC patients. Clinical results of the first 12 vaccinated patients showed radiological stable disease in 67% of patients at 6 months."

Clinical • Prostate Cancer

A phase 2 study of CMB305 and atezolizumab in NY-ESO-1+ soft tissue sarcoma: Interim analysis of immunogenicity, tumor control and survival (ESMO 2017) - P2; "In the interim analysis, Arm A+C resulted in a higher level of anti-NY-ESO-1 IR when compared to Arm A; pts with IR tend to have better target lesion control. Early data indicate that induction of anti-NY-ESO-1 IR may be associated with better survival."

Clinical • P2 data • Sarcoma

A pilot study of NY-ESO-1c259 T cells in subjects with advanced myxoid/round cell liposarcoma (NCT02992743). (ASCO 2017) - P1/2; "Response is assessed at 4, 8, 12 and 24 weeks, and then every 3 months until confirmation of progression of disease. On study tumor biopsies and blood samples will be evaluated to compare the pre- and post-T cell infusion immune profile for association with treatment outcome."

Clinical • Biosimilar • Sarcoma

Open label, non-randomized, multi-cohort pilot study of genetically engineered NY-ESO-1 specific NY-ESO-1c259t in HLA-A2+ patients with synovial sarcoma (NCT01343043). (ASCO 2017) - P1/2; "NY-ESO-1c259T has promising efficacy and acceptable safety. CRS is not associated with severe neurotoxicity and appears manageable with appropriate supportive care. Cohort 3 data indicate that Flu may be important for efficacy."

Adverse events • Biomarker • Clinical • Biosimilar • Epilepsy • Sarcoma • Venous Thromboembolism

A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles for potent melanoma immunotherapy (AACR 2017) - P1; "Following selective antigen stratification on routinely collected tumor samples, eligible patients with malignant melanoma are treated with increasing doses of the tetravalent Lipo-MERIT vaccine - a fixed set of four RNA(LIP) products, each encoding one shared melanoma-associated antigen, i.e. NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, that are administered successively within one treatment cycle. Further patient enrollment is continuing. Detailed information on the ongoing trial, the recruitment and treatment status as well as preliminary data on the assessment of vaccine-induced immune responses from the first patients treated will be presented."

Biomarker • Clinical • P1 data • P1/2 data • Biosimilar • Oncology

Two phase I/II open label clinical trials evaluating the safety and efficacy of autologous T cells expressing enhanced TCRs specific for NY-ESO-1 or MAGE-A10 in subjects with stage IIIb or stage IV non-small cell lung cancer (NCT02588612/NCT02592577). (ASCO 2017) - P1/2,P=N/A; "These studies will evaluate the safety and antitumor activity of genetically engineered affinity enhanced TCRs (NY-ESO-1c259T or MAGE-A10c796T) directed towards a NYESO-1 or MAGE-A10 derived peptides complexed with HLA-A*02. The MAGE-A10c796T first-in-human study is a modified 3+3 design in up to 28 pt with escalating doses of 0.1, 1.0 and 1-6 x 109 transduced T cells, with staggered treatments to allow for safety review; dose escalation will be guided by the DLT observed and by safety review committee guidance. Response to treatment will be assessed by RECIST v1.1 at weeks 4, 8, 16, 24, every 3 months (for 2 yr) and every 6 months until disease progression."

Checkpoint inhibition • Clinical • P1/2 data • Biosimilar • Immunology • Non Small Cell Lung Cancer

Immune response, safety, and survival impact from CMB305 in NY-ESO-1+ recurrent soft tissue sarcomas (STS). (ASCO 2017) - P1b; "Clinical trial information: NCT02387125 CMB305 is safe, well tolerated, and demonstrates a survival rate that is favorable when compared with approved agents for recurrent STS. CMB305 resulted in a stronger and broader integrated IR than LV305, including antigen spreading. These data warrant further investigation of CMB305 as a monotherapy in a randomized clinical study in STS."

Adverse events • Clinical • Biosimilar • Non Small Cell Lung Cancer • Ovarian Cancer • Pain • Sarcoma

A phase I/IIa, open label, clinical trial evaluating the safety and efficacy of autologous T cells expressing enhanced TCRs specific for NY-ESO-1 in patients with recurrent or treatment refractory ovarian cancer (NCT01567891). (ASCO 2017) - P1/2; "Following apheresis, the T cells are isolated and expanded with CD3/CD28 beads, transduced with a lentiviral vector containing the NY-ESO-1c259 TCR, and 1 – 6 × 109 transduced T cells are infused intravenously on Day 0 after lymphodepletion with fludarabine 30 mg/m2/day and cyclophosphamide 600 mg/m2/day on days -7 to -5. Response is assessed at weeks 4, 8, 12 and 24, and then every 3 months until confirmation of disease progression."

Clinical • P1/2 data • Biosimilar • Ovarian Cancer

Randomized phase II trial of a first-in-human cancer cell lysate vaccine in patients with thoracic malignancies. (PubMed, Transl Lung Cancer Res) - "Eight of 14 patients (57%) exhibited serologic responses to NY-ESO-1. Cyclophosphamide/celecoxib did not appear to increase immune responses or enhance vaccine-induced alterations in peripheral immune subsets. H1299 lysate vaccines with Iscomatrix™ induce immune responses to CTA and modulate peripheral immune subsets in a manner that may enhance antitumor immunity in patients with thoracic malignancies."

Clinical • IO biomarker • Journal • P1 data • P2 data • Immunology • Inflammation • Lung Cancer • Oncology • Solid Tumor • Systemic Inflammatory Response Syndrome • Thoracic Cancer • CD14 • CTAG1B • PD-1 • PD-L1

Immunogenicity of HspX/EsxS fusion protein of Mycobacterium tuberculosis along with ISCOMATRIX and PLUSCOM nano-adjuvants after subcutaneous administration in animal model. (PubMed, Microb Pathog) - "With regard to ability of ISCOMATRIX, PLUSCOM and MPLA adjuvants to increase immunogenicity of HspX/EsxS protein through induction of IFN-γ and IgG2a immune responses, it seems that these adjuvants and especially ISCOMATRIX and PLUSCOM, could also improve BCG efficacy as a BCG booster."

Journal • Preclinical • Infectious Disease • Respiratory Diseases • Tuberculosis • IFNG • IL17A • IL4 • TGFB1

Protection against the New Equine Influenza Virus Florida Clade I Outbreak Strain Provided by a Whole Inactivated Virus Vaccine. (PubMed, Vaccines (Basel)) - "From these results, it can be concluded that Equilis Prequenza provides a high level of protection to challenge with the new FC1 outbreak strain. This suggests that, apart from antigenic differences between vaccine and field strain, other aspects of the vaccine may also play an important role in determining field efficacy."

Journal • Infectious Disease • Respiratory Diseases

Protection against Toxoplasma gondii cysts in pigs immunized with rROP2 plus Iscomatrix. (PubMed, Rev Bras Parasitol Vet) - "In conclusion, there were not systemic antibody responses in pigs with IN immunization with rROP2+Iscomatrix; however, after IM immunization, those animals produced higher titers than animal controls. We associated these results with partial protection obtained against parasitemia and tissue cysts formation."

Journal • Anorexia

Therapeutic ISCOMATRIX™ adjuvant vaccine elicits effective anti-tumor immunity in the TRAMP-C1 mouse model of prostate cancer. (PubMed, Cancer Immunol Immunother) - "NK cells, CD4 T cells and interferon-γ were all found to be critical for tumor control while tumor infiltrating CD8 T cells became disabled by an immunosuppressive microenvironment. There is potential for broader application of this cancer vaccine, as we have been able to demonstrate effectiveness in two additional cancer models; melanoma (B16-OVA) and a model of B cell lymphoma (Eµ-myc-GFP-OVA)."

Journal • Genito-urinary Cancer • Lymphoma • Melanoma • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer

Determining Equine Influenza Virus Vaccine Efficacy-The Specific Contribution of Strain Versus Other Vaccine Attributes. (PubMed, Vaccines (Basel)) - "Vaccination induced protective antibody titres to FC1 and FC2 and reduced clinical signs and viral shedding. The two tested vaccines provided equivalent protection against a recent FC2 EIV field strain."

Clinical • Journal • Infectious Disease • Respiratory Diseases

Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2; N=78; Not yet recruiting; Sponsor: National Cancer Institute (NCI)

New P1/2 trial • Biosimilar • Non-Hodgkin’s Lymphoma • Ovarian Cancer

Adjuvant Tumor Lysate Vaccine and Iscomatrix With or Without Metronomic Oral Cyclophosphamide and Celecoxib in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum (clinicaltrials.gov) - P1/2; N=21; Suspended; Sponsor: National Cancer Institute (NCI); Trial completion date: Nov 2023 ➔ Nov 2028; Trial primary completion date: Nov 2023 ➔ Nov 2028

Clinical • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Oncology • Sarcoma • Solid Tumor • Thoracic Cancer

Expansion of cancer germline antigen-specific cytotoxic T lymphocytes for immunotherapy. (PubMed, Tumour Biol) - "The cancer germline antigens MAGE-A1, MAGE-A3, and NY-ESO-1 can be used to target relapsed or therapy-resistant malignant solid tumors, and previous studies have demonstrated that these antigens can be epigenetically upregulated on the surface of tumor cells following exposure to low-dose demethylating chemotherapy agents, such as decitabine. High-density lymphocyte culture prior to stimulation with cancer germline antigen peptides resulted in antigen-specific cytotoxic T lymphocyte from healthy donors and patients from whom cancer germline antigen cytotoxic T lymphocyte culture with conventional methods was not feasible. These data demonstrate that MAGE-A1-, MAGE-A3-, and NY-ESO-1-specific T cells with antigen-specific cytotoxicity can be cultured from healthy donors and patient-derived cells making adoptive immunotherapy with these cytotoxic T lymphocyte feasible."

Journal • Biosimilar • Solid Tumor

Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma Treated with Ipilimumab and an IDO-Silenced Dendritic Cell Vaccine. (PubMed) - Case Rep Med - "The patient also mounted an antibody response to several melanoma proteins, indicating diversification of the antitumour immunity in this patient. The identification of such serum antibody-reacting proteins could facilitate the discovery of tumour neoantigens."

Journal • Biosimilar • Melanoma • Oncology

Study of NY-ESO-1 ISCOMATRIX in patients with measurable stage III or IV melanoma (clinicaltrials.gov) - P2, N=16 -> 46; Active, not recruiting -> Completed; Completion date: Apr 2010 -> Nov 2012.

Enrollment change • Trial completion • Trial completion date • Melanoma

Phase I Study of Safety and Immunogenicity of ADU-623 (clinicaltrials.gov) - P1; N=11; Active, not recruiting; Sponsor: Providence Health & Services; Recruiting ➔ Active, not recruiting; N=38 ➔ 11

Enrollment change • Enrollment closed • Biosimilar • Immunology • Oncology • Solid Tumor

CT Antigen TCR-Engineered T Cells for Myeloma (clinicaltrials.gov) - P1/2; N=10; Recruiting; Sponsor: Adaptimmune; Trial primary completion date: Apr 2016 ➔ Apr 2017

Trial primary completion date • Biosimilar • Hematological Malignancies • Multiple Myeloma • Oncology

Immunological characteristics of the tumor-associated antigens in patients with cholangiocarcinoma (AASLD 2016) - "We examined the expression of TAAs, which included Cyp-B, Lck, SART1, SART2, SART3, p53, MRP3, hTERT, VEGFR1, VEGFR2, Survivin, MAGE-A4, Her2, WT1, βcatenin, CEA, EpCAM, EZH2, MUC5AC, GPC3, NYESO1, KIF20A, ART4 and AKR1C3, by real-time PCR in cholangiocarcinoma cell lines and human tissues including intrahepatic, extrahepatic bile duct and gallbladder cancer. Taken together with these results, SART1, MRP3, Survivin2B, MAGEA3, MAGEA4, Her2, βcatenin, CEA, EpCAM, GPC3 and KIF20A were considered to be immunogenic and specific for cholangiocarcinoma. SART1, MRP3, Survivin2B, MAGEA4, Her2, βcatenin, CEA, EpCAM, GPC3 and KIF20A were useful targets of immunotherapy for cholangiocarcinoma."

Biliary Cancer • Biosimilar • Bladder Cancer • Gastrointestinal Cancer • Oncology • Urothelial Cancer

The novel immunogenic chimeric peptide vaccine to elicit potent cellular and mucosal immune responses against HTLV-1. (PubMed, Int J Pharm) - "Furthermore, the SC or nasal delivery of various vaccine formulations could shift the immunity toward cell-mediated responses, as evident by higher IgG2a and IFN-γ, as well as suppressed TGF-β1 level. Our findings suggest that proper design, construction, and immunization of multi-epitope vaccine are essential for developing an effective HTLV-1 vaccine."

Journal • Biosimilar

Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant: Safety and Tolerability. - PLoS One - "Our findings suggest that vaccines adjuvanted with either QS-21 or ISCOMATRIX posed no specific safety concern. Furthermore, our results indicate that the use of ISCOMATRIX enables a better systemic tolerability profile when compared to the use of QS-21. However, no better local tolerance was observed for ISCOMATRIX-adjuvanted vaccines in immunized non-healthy subjects. This meta-analysis is limited by the relatively small number of individuals recruited in the included trials, especially in the control groups."

Journal • Biosimilar • Pain

A pilot study of peripheral blood BDCA-1 (CD1c) positive dendritic cells pulsed with NY-ESO-1 ISCOMATRIX™ adjuvant. (PubMed) - "This method was feasible and safe but was minimally immunogenic."

Journal • Biosimilar • Oncology