Oslo, Norway, 11 September 2017: Targovax ASA ("Targovax" or "the Company"; OSE: TRVX), a clinical stage company focused on developing immuno-oncology therapies to target solid tumors, today announces that three posters were presented during the European Society for Medical Oncology (ESMO) Congress in Madrid, Spain, from September 8-12.
Oystein Soug, Chief Executive Officer of Targovax, said, "The ESMO annual conference is a place where clinicians and researchers from all over the world gather to share important information with the goal of finding effective cancer treatments. We are delighted that ESMO allowed us to participate with three posters in this important forum."
"The data in the posters we presented highlight some of the important progress we have made to date in the clinic with our two novel proprietary immunotherapy technology platforms. The two posters summarizing the encouraging data from early clinical studies with TG01, from the neo-antigen therapeutic cancer vaccine platform, suggest it may have significant potential in the treatment of RAS-mutated pancreatic cancer, which currently has a poor prognosis. The third poster relates to an ongoing phase I/II study in mesothelioma, a rare and difficult to treat cancer, with the lead drug candidate from our oncolytic virus platform, ONCOS-102."
The complete poster abstracts can be found below.
An observational clinical study with RAS peptide vaccine TG01 evaluating immune response, safety and overall survival in patients with non-resectable pancreatic cancer
Background: The study evaluated the immune response, safety and survival of the TG01/GM-CSF vaccine, an antigen-specific cancer immunotherapy consisting of 7 RAS peptides targeted to KRAS mutated pancreatic adenocarcinoma, in treatment naive non-resectable pancreatic cancer patients. TG01/GM-CSF was recently reported to elicit immune response and increased survival in resectable pancreatic patients (ASCO 2017).
Methods: 25 treatment naive non-resectable pancreatic cancer patients were immunised with TG01/GM-CSF at week 1, 2, 3, 4, 6, 10 (immunisation period) followed, after a 3 months pause, by a booster period of four weekly administrations. Patients were followed up for up to 12 months from 1st dose of TG01/GM-CSF. Immune response was evaluated by Delayed Type Hypersensitivity (DTH) skin reaction test, (S)AEs recorded throughout the study and survival data calculated using Kaplan-Meier.
Results: 14/25 patients (56%) had a positive DTH by week 10. The TG01/GM-CSF treatment was well tolerated with no reports of allergic or other adverse hypersensitivity reactions. 13 patients experienced 19 SAEs; 5 were due to disease progression, 13 were deaths due to disease progression, and one was treatment related (hypoglycaemia). Median survival (MS) from first administration of TG01/GM-CSF was for all treated patients (n=25) 4.5 months, for DTH responders (n=14) 5.1 months and for DTH non-responders (n=11) 3.6 months. For the DTH responders the result compares favorably with untreated patients (MS ~ 3.7 months)1. At 1 year, 4 patients of whom three DTH responders were alive.
Conclusions: In patients treated with TG01/GM-CSF monotherapy, immune response was recorded in 56% of the patients, results that correspond with data from a Phase I/II trial with a similar RAS peptide vaccine in non-resectable pancreatic patients2. Even though not statistically significant, the results indicate increased survival for the immune responders. In the otherwise incurable disease, the non-resectable pancreatic patients may therefore benefit from immunisation with TG01/GM-CSF RAS peptide vaccine with few side effects.
TG01/GM-CSF and adjuvant gemcitabine in patients with resected RAS-mutant adenocarcinoma of the pancreas
Background: The study evaluated the immune response, safety and clinical efficacy of the TG01/GM-CSF vaccine, an antigen-specific cancer immunotherapy consisting of 7 RAS peptides targeted to KRAS mutated pancreatic adenocarcinoma (PAC). The efficacy of adjuvant chemotherapy in resected disease is limited with 1- and 2-year published overall survival (OS) rates ranging from 56-80% and 30-54% respectively. TG01 induces RAS mutant-specific T-cell responses which are enhanced by co-administration of GM-CSF.
Methods: Patients were eligible after R0 or R1 PAC resection. As soon as possible after surgery, TG01 (0.7 mg intradermal injection (id)) together with GM-CSF (0.03 mg id) was given on days 1, 3, 5, 8, 15, 22 and 2-weekly thereafter until the end of gemcitabine (starting within 12 weeks of surgery and given for 6 cycles). Thereafter TG01/GM-CSF was given 4-weekly up to 1 yr and 12-weekly up to 2 yrs. Immune response was assessed using antigen-specific (TG01) Delayed-Type Hypersensitivity and T-cell proliferation. OS and disease free survival (DFS) was assessed from surgery; ~8 weeks before first TG01 injection.
Results: To date, 19 patients (68% R1) have been followed for 2 1/2 yrs. Median CA19-9 was 15 (5, 240) U/ml at baseline. 8 SARs in 5 patients have occurred; 4 related to gemcitabine (anemia, pulmonary infection and 2 fever); 3 related to TG01/GM-CSF (2 anaphylaxes and 1 hypersensitivity); and 1 possibly related to all products (dyspnea). The allergic reactions only occurred after several cycles of gemcitabine and resolved within 1-2 hrs. There were no treatment related deaths. TG01 induce an immune response in 17/19 patients by week 11, which demonstrate that TG01 vaccination activate TG01 specific T-cells. OS rate at 2 yrs was 68.4 (95% CI 47.5, 89.3). OS rate at 2 1/2 yrs will be presented. Median OS was 33.1 months (95% CI 16.8, 40.1). Median DFS was 13.9 months (95% CI 5.4-21.0)
Conclusions: The regimen was generally well tolerated although some late, manageable allergic reactions were seen. OS and DFS was encouraging in view of published reports. TG01/GM-CSF generated early immune responses in 89% of patients with R0/R1 resected pancreatic cancer. 13 patients have been recruited in a modified dose cohort with 2 yrs data in 2Q 2018.
ONCOS-102 and pemetrexed/cisplatin in patients with unresectable malignant pleural mesothelioma
Background: Mesothelioma is a rare cancer with poor prognosis and limited treatment options, including surgery, radiotherapy and chemo (pemetrexed + cisplatin/carboplatin). Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. ONCOS-102 is a granulocyte-macrophage colony stimulating factor (GM-CSF) - expressing oncolytic adenovirus (Ad5/3-D24-GMCSF). In a prior phase I study of 12 patients with advanced solid tumors, 40% had stable disease (SD) at 3 months, 11/12 patients had infiltration of CD8+ lymphocytes in lesions, and 10/12 had intralesional PD-L1 expression increase. Lesional immune activation was seen in two patients with mesothelioma.
Trial Design: A randomized Phase II study (n=24) with a non-randomized Phase Ib safety lead-in cohort (n=6). The study will compare ONCOS-102 and chemo with chemo alone (control arm). Eligible patients have histologically confirmed unresectable disease and are not candidates for curative surgery. Patients can be naïve to chemo, or have received and responded to chemo, but relapsed after at least 6 months thus eligible for renewed chemo treatment. Patients must have measurable disease with tumour accessible to intratumoural injections of ONCOS-102 and biopsies. A Data Safety Monitoring Committee will review data when the first 3 and all 6 patients have completed the Day 64 visit (i.e. after 2 cycles of chemo and 4 injections of ONCOS-102). If safety is acceptable, phase II will start with 10 patients in the control arm, and 14 patients in the experimental arm.
Primary objective: Safety. Secondary objectives: 1) Tumour specific immunological activation in peripheral blood and biopsies 2) Response Rate 3) Progression Free Survival 4) Overall Survival and 5) Correlation between immune activation and clinical outcome.
Treatment: Single cyclophosphamide dose followed by intratumoral injection of ONCOS-102 at 3x1011viral particles (VPs) on days 1, 4, 8, 36, 78 and 120. Pemetrexed (500mg/m2)/cisplatin(75mg/m2) is given on day 22 and every 3 weeks for a maximum of 6 cycles. Imaging at baseline, Day 64 and 148. Tumor biopsies from both injected and non-injected lesions at baseline and Day 36.
The abstract can be found on www.targovax.com.
In addition, the abstracts have also been published in the ESMO 2017 Congress Abstract Book, a supplement to the official ESMO journal Annals of Oncology.
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Arming the patient's immune system to fight cancer
Targovax is a clinical stage company focused on developing and commercializing novel immuno-oncology therapies to target, primarily, treatment-resistant solid tumors. Immuno-oncology is currently one of the fastest growing therapeutic fields in medicine.
The Company's development pipeline is based on two novel proprietary platforms:
The first platform, ONCOS, uses oncolytic viruses as potential multi-target, neo-antigen therapeutic cancer vaccines. ONCOS exclusively uses an adenovirus that has been engineered to be an immune activator that selectively targets cancer cells. In phase I studies it has demonstrated immune activation at lesional level which was associated with clinical benefit. In an ongoing phase I trial in advanced melanoma we expect important proof of concept data for checkpoint inhibitor refractory patients.
The second, TG, is a target specific, neo-antigen therapeutic cancer vaccine platform that solely targets tumors that express mutated forms of the RAS protein. Mutations to this protein are common in many cancers and are known to drive aggressive disease progression and treatment resistance. There is a high unmet medical need for therapies that are effective against tumors that express these mutations. The TG platform's therapeutic potential stems from its ability to enable a patient's immune system to identify and then destroy tumors bearing any RAS mutations. In early 2017, key proof of concept data for the TG platform from a clinical trial of TG01 in resected pancreatic cancer patients showed encouraging overall survival and will give guidance for the future clinical development of this platform.
Targovax's development pipeline has three novel therapeutic candidates in clinical development covering six indications.
Both platforms are protected by an extensive portfolio of IP and know-how and have the potential to yield multiple product candidates in a cost-effective manner. Additionally, Targovax has other products in early stages of development.
In July 2016, the Company listed its shares on Oslo Axess. In March 2017, the shares moved to Oslo Børs, the main Oslo Stock Exchange.
About ESMO 2017 Congress
The European Society for Medical Oncology (ESMO) is the leading professional organisation for medical oncology. The ESMO 2017 Congress, in partnership with the European Association for Cancer Research (EACR), will bring cancer researchers and clinicians together to enable collaboration and the exchange of ideas, from the laboratory to the bedside and back. This exciting partnership creates a unique cancer congress in Europe with huge scientific reach and the true potential to improve the lives of cancer patients. The ESMO Congress is the most influential annual meeting for oncology professionals in Europe.
For more information, visit: http://www.esmo.org/.
This information is subject to the disclosure requirements pursuant to section 5-12 of the Norwegian Securities Trading Act.