Mesothelioma Research News interviewed Angelos Stergiou, MD, ScD, CEO and vice chairman of the board, and Nicholas Sarlis, MD, PhD, senior vice president and chief medical officer of Sellas Life Sciences Group, to know more about the upcoming Phase 3 trial investigating the efficacy and safety of galinpepimut-S in patients with malignant pleural mesothelioma (MPM).
An in-depth article on this interview, with more information about galinpepimut-S and ongoing clinical trials MPM and other cancer patients can be found here.
Q: The Phase 2 study investigating the efficacy of the galinpepimut-S vaccine showed promise for this treatment in patients with malignant pleural mesothelioma (MPM), such as 24.8-month overall survival compared to 16.6 months in a control group. For the Phase 3 trial, is there a particular group of MPM patients Sellas intends to enroll, and how many in total are you hoping to enroll?
A: In our phase 3 clinical trial, we plan to include patients with mesothelioma with disease on one side of the chest (right or left) who would have been able to complete initial treatment with surgery and chemotherapy. The initial surgery should have resulted in removal of all the visible primary cancer and any local surrounding tumor-containing lymph nodes. The chemotherapy could have been given either before the actual surgery (called ‘neoadjuvant’ or ‘induction chemo) or after that (called ‘adjuvant’ or ‘postoperative’ chemo). Some patients may have also undergone radiation therapy (radiotherapy), but this would not be mandatory for participation in the study. Galinpepimut-S (active therapy) or placebo would be given to patients as early as three weeks but no longer than three months after the completion of the initial surgery plus chemotherapy combination.
We are hoping to enroll a minimum of 150 patients, but the study could potentially include up to 400 patients, depending on whether certain criteria are met when we ‘look’ at pre-set intervals on how the study evolves. Each patient would be receiving active treatment for at least 13-18 months.
Q: What clinical measures will be used to assess the efficacy of the vaccine in these patients?
A: The key measure of deciding upon whether galinpepimut-S offers clinical benefit will be overall survival at the time of the final analysis. Our assumptions are that adding our therapy will result – on average- in patients living at least eight months longer in comparison to what would be expected with standard therapy today.
Importantly, we will also perform an additional earlier check to assess how quickly we see relapsed (recurrent) disease in patients on either group in the trial. The rate of progression at the time of that evaluation will determine how to best proceed with the rest of the study afterward. Disease progression would be based on detection of tumor recurrence (relapse) by body imaging studies, more specifically CT-PET scans.
Q: Why should MPM patients be interested in joining this Phase 3 trial, when it opens approximately later this year?
A: Galinpepimut-S is designed to act exactly during the period of high risk for recurrence and could significantly delay the re-occurrence of the disease but, more importantly from what we have seen, it seems to prolong survival; this could be translated into an at least eight-month benefit in additional lifespan. Given the above, that is the complete lack of an effective maintenance therapy to prevent tumor relapses, as well as the very favorable safety profile of galinpepimut-S, in addition to predicted survival benefit, we believe that MPM patients (and their treating physicians) would be very interested in participating in our trial.
Q: Is there an estimate as to when this trial will start recruiting patients? In which countries? Is it particularly difficult recruiting patients with less common and aggressive cancers, like MPM?
A: We are hopeful that we’ll be able to start activation of the various sites that will commit to participate in this study by the end of 2017 as it is also subject to financing. We plan to enroll patients in North America (U.S. and Canada), as well as several European countries and potentially Australia.
MPM is both a rather uncommon and also rapidly advancing malignancy, which makes recruitment in clinical trials in this disease challenging. The “window of opportunity” to enroll in the trial is also rather narrow, as in some MPM patients tumor relapses can occur much earlier than 14-16 months after completion of their initial upfront therapy (surgery plus chemotherapy).
Q: When are the first results expected to be known?
A: In our phase 3 trial, we have used an innovative statistical analysis design, so that we can gauge a potential positive signal of clinical activity as early as possible. Therefore, if there are early indications of clinical benefit with regard to overall survival and/or delayed progression-free survival by giving galinpepimut-S, this could lead to stopping at the second interim analysis and declaring the study as ‘positive’.
Q: This vaccine is noted as being a possible part of a combination treatment for 20 different cancers, many difficult or advanced (MPM, ovarian, multiple myeloma, etc.). Can you please talk about what combinations this vaccine seems to be most effective in, and why you think the vaccine will have such a broad treatment scope?
A: The active immunization we are utilizing with galinpepimut-S is targeting a protein called Wilms Tumor-1 or WT1. This protein is very widely present (“expressed”) in human cancers of various different types, not only in the actively dividing cancer cells, but also cancer stem cells. WT1 acts a cell division stimulant, that is has the function of a true “oncogene” and is not merely a “marker” of cancer. Therefore, targeting WT1 is of fundamental importance for the control of cancer growth. The human immune system is only extremely minimally reactive against the WT1 antigen under normal circumstances, as this protein is not present in any appreciable amounts in normal organs and cells.
The galinpepimut-S active immunizing peptide mixture could be given as monotherapy (as a single agent) or in combination with other anticancer therapies. In the first instance, we believe our approach would be most efficacious when the tumor burden/ malignant cell load is as low as can be in each given patient when the patient’s body raises an immune attack. The majority of the tumor has been already “mopped up” by previous surgery and chemotherapy. Galinpepimut-S could very easily be combined with other anticancer therapies, particularly those that are activating the immune system. These new cancer immunotherapies, such as the newly introduced in the clinic “checkpoint inhibitors” (e.g., drugs blocking the PD1 or PDL1 protein, such as nivolumab, pembrolizumab, atezolizumab and several others). This would potentially lead to strong, sustained and clinically effective immune responses, and could lead to very powerful tumor killing and evidence of clinical regression of existing measurable tumor deposits. This would mean that galinpepimut-S in combination with checkpoint inhibitors could be used for the primary (upfront) therapy of a wide variety of tumors, thus providing effective anticancer therapy — and importantly survival outcomes, and hope — for a great number of patients in whom immunotherapy with checkpoint inhibitors alone does not offer significant benefit today. We have started such a combination trial in ovarian cancer and will have early data available later this year.
Q: How many different types of cancers are you currently studying this vaccine in? Have you plans to expand to new cancer types in the near future — perhaps this year and next?
A: We have studied galinpepimut-S in acute myeloid leukemia, mesothelioma, multiple myeloma and, more recently, ovarian cancer. We are planning to study this approach in several other cancer types, including a specific subtype of colorectal cancer, lung cancer (non-small cell and possibly also small cell lung carcinoma), and potentially a brain malignancy called glioblastoma multiforme, and also chronic myeloid leukemia. Other possible tumor types that could be potentially targeted include certain soft tissue malignancies (sarcomas), a very rare blood cancer called plasma cell leukemia, or head and neck cancer. The majority of these potential trials are currently in the planning stage, where we are examining the realistic feasibility of running all these studies.
As one could imagine, some of these trials could be run in combination with other novel therapies, and indeed we are in the process of soliciting the potential collaboration of other biotechnology and pharmaceutical companies, so that we could carve out a reasonable collaborative approach that could lead to easier and faster clinical study execution and could bring forth fruitful results at the earliest possible. Further announcements on the starting of at least some of these trials will be forthcoming within this year.
Q: Sellas also started a Phase 3 trial of the vaccine in acute myeloid leukemia (AML) this year, a Phase 2 trial in multiple myeloma is ongoing, and has a number of Phase 1 trials either ongoing or planned (ovarian cancer in combination with Opdivo, and studies in chronic myelogenous leukemia (CML) and glioblastoma multiforme. Can you give up some update on these studies?
A: We are prepared to initiate the Phase 3 large global clinical study of galinpepimut-S in patients with AML after initial induction chemotherapy and achievement of their first complete remission (CR1); this study will focus only on patients older than 60 years of age. This will be a global effort, which could provide preliminary efficacy results as early as toward the end of 2019, which, if positive, could potentially lead to a new product registration (after discussion with and positive decision by regulatory authorities). The study is ready to start by around end of Q2/early Q3 this year.
A phase 1/2 study is currently underway in patients with recurrent ovarian cancer after their first (or subsequent) successful ‘salvage’ therapy (with no measurable residual disease after that therapy). In this study, we combine galinpepimut-S with the checkpoint inhibitor nivolumab (Opdivo). This study has already accrued more than half of its total number of patients, and it will report both immune response effects of the combination treatment as well as clinical outcomes later this year and next.
Q: If all goes well with the Phase 3 studies for MPM and AML, is Sellas planning on submitting applications to the FDA and EMA for regulatory approval?
A: Assuming the corresponding phase 3 studies in AML and MPM successfully meet their predefined endpoints and the studies are indeed declared positive, Sellas is committed to work diligently with both the FDA and EMA to ensure filing of applications based on these clinical data aiming at regulatory registration/ market authorization in the respective territories as quickly as possible.