A cancer vaccine based on arenavirus vectors announces positive results in a phase 1 trial, and medical doctor Mai Meng broke the news for HPV 16-positive cancers

Recent popular reports from Yimaike ★ Invitation to the event2021 Oncolytic Virus Drug Development Forum is about to open in Shanghai ★ The financing has been hundreds of millions in half a year, and the oncolytic virus has entered the fast laneYimai New Observation Click on the picture and register now June 9, 2021 /Healthcare News eMedClub News/--On June 7, 2021, HOOKIPA Pharma, a company that develops new immunotherapeutics based on its proprietary arenavirus platform, reported its ongoing HB- at the ASCO annual meeting in 2021.
Positive data in the Phase 1 phase of the Phase 1/2 study of 201 in the treatment of advanced human papillomavirus 16 positive (HPV16+) cancers
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About 5% of the world's cancer burden is caused by the HPV virus
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99% of cervical cancers, up to 60% of head and neck cancers, 70% of vaginal cancers, and 88% of anal cancers are caused by HPV and most are caused by type 16 HPV
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 In some cases, HPV DNA will be integrated into chromosomal DNA
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When host cells take up this DNA, they express HPV E6 and E7 proteins
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The expression of these proteins can lead to changes in cell cycle control, making these cells prone to cancer
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HB-201 and HB-202 are two vaccines based on arenavirus vectors developed by HOOKIPA
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Each single vector compound uses a different arenavirus backbone: HB-201 uses lymphocytic choriomeningitis virus (LCMV); HB-202 uses Pichinde virus (PICV)
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Both express the same antigen, namely the non-carcinogenic but highly antigenic E6/E7 fusion protein derived from HPV16
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 In pre-clinical studies, it has been observed that alternate use of HB-201 and HB-202 can increase the immune response by 10 times, and can control the disease better than using either compound alone
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In the company’s oral report (Abstract #2502), it was mentioned that the phase 1 trial of HB-201 in the treatment of HPV16+ cancer patients showed that the immune response of T cells was outstanding.
As a monotherapy, HB-201 should be used for those receiving standard treatment (including In patients with advanced over-pretreatment after checkpoint inhibitors), preliminary effects can be seen and well tolerated
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The company also published transformational data, showing a relationship between T cell response and potential clinical efficacy
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HB-200 trial (NCT04180215) In December 2019, the company launched a phase 1/2 clinical trial (NCT04180215) for the treatment of HPV16+ cancer patients with HB-201
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In October 2020, as part of the HB-202/HB-201 sequential alternation protocol in this trial, the test patients were injected with HB-202 for the first time
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 Recommended reading: Cancer vaccines based on arenavirus vectors have officially entered the clinic, targeting HPV 16-positive cancersYi Meng broke the news.
This trial is for HB-201 single-vector therapy and HB-201/HB-202 dual-vector therapy in HPV A phase 1/2 multinational, multi-center, open-label study conducted in 16+ diagnosed cancer patients
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The trial consists of two parts: the first phase of dose escalation, and the second phase of dose expansion
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 In the phase 1 trial, the single-vehicle treatment group and the dual-vehicle treatment group each included two groups of test patients, and the drug-limited toxicity was evaluated
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The phase 2 trial will include up to 6 treatment groups, and the primary endpoint is the objective response rate and disease control rate after the patient has progressed
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 As of March 31, 38 patients with metastatic HPV16+ tumors received HB-200 treatment: 14 patients received HB-201 intravenous injection every three weeks, and 8 received alternate intravenous injections of HB-201/HB-202 every three weeks.
16 patients received other protocols
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 Most patients (32) have squamous cell head and neck tumors; patients with other tumor types include 3 patients with cervical cancer, 1 patient with vaginal cancer, 1 patient with anal cancer, and 1 patient with penile cancer
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 The data published in the trial mainly include: preliminary efficacy results, safety results and immunogenicity results
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Preliminary efficacy results: Phase 1 data shows promising treatment duration: At the data cutoff, the median number of days for patients to start injecting HB-201 was 127 days, and the median number of days to start injecting HB-201/HB-202 For 87 days
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Compared with dose level 1, HB-201 dose level 2 may lead to longer treatment time, and the two dose level trials of HB-201/HB-202 are still in progress
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 The target lesions were controlled in 93% (14/15) of patients, and the target lesions were reduced in 53% (8/15 patients)
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Two of the 14 patients had disease progression in other parts, and the overall disease control rate was 80% (12/15 patients)
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In addition, HB-201 showed a disease control rate of 73% (8/11 patients), 2 patients had partial response, 6 patients were in stable condition, and 4 of them were in stable condition for more than 16 weeks
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The preliminary data of HB-201/HB-202 show that the disease control rate is 100% (4/4)
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 So far, data on patients with over-pretreatment of HB-201 monotherapy have shown an overall response rate of 18% and a median progression-free survival (PFS) of 3.
45 months
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82% (31) of the patients had progressed in the PD-1 inhibitor regimen
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79% of patients shifted from baseline to distant places, and the performance of refractory patients was more prominent
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 Safety results: Phase 1 data of 38 evaluable patients showed that HB-200 therapy has good safety in HPV16+ cancer patients who have undergone over-pretreatment, highlighting its use as a monotherapy and possible combination with PD-1 inhibitors Potential to use
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53% of patients reported treatment-related adverse events
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There were no serious adverse events, no dose-limiting toxicity, and no treatment-related adverse events of grade 3 or higher
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In addition, there were no discontinuations, dose changes, or interruptions due to treatment-related adverse events
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The most common side effects are fatigue (32%), fever (26%), nausea (18%) and high blood pressure (16%)
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 Immunogenicity results: Preliminary data show that the new arenavirus therapy HB-200 therapy is highly immunogenic, which can induce and activate tumor antigen-specific CD8+ T cells to an unprecedented level, accounting for an average of 6% of the T cell pool, and the highest possible Up to 40%
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 At baseline, tumor-specific T cell levels were almost undetectable in all patients
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Within two weeks of a single dose of HB-201, all patients showed elevated levels of tumor-specific CD8+ T cells; the immune response levels of all patients far exceeded the lower limit of the quantitative standard, and many were close to the quantitative standard.
Upper limit
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 Importantly, these results are based on direct ELISpot without the need for ex vivo expansion of T cells, highlighting the extent of T cell responses produced by HB-201 treatment (in vitro expansion is usually used to amplify the reaction, otherwise it cannot be measured)
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Alan L.
Ho, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, said: “The treatment options for patients with advanced HPV16+ cancer are limited, and there is no established standard of care after the use of PD-1 inhibitors
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Usually the remission rate will be With subsequent treatment lines decline, it is encouraging to see that active immunotherapy (such as HB-201 single-vector therapy) produces objective remission in a large number of pre-treated patients
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In addition, it is encouraged by HB-201/HB-202 The induced high levels of antigen-specific CD8+ T cells prove that the drug has the potential to transform immunogenicity into clinical curative effect
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"Arenavirus is a naturally occurring virus family, and more than 30 kinds are known for decades.
It has been used as a preclinical tool for studying T cell responses
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As an antigen-specific immunotherapy, Arenavirus has many advantages
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 For more details, please click on the QR code below to read the reference materials: 1.
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