VITALIZE Trial Explores Maveropepimut-S/Pembrolizumab in Relapsed/Refractory DLBCL

Matthew Matasar, MD

The phase 2b VITALIZE study (NCT04920617) of maveropepimut-S (DPX-Survivac) in combination with pembrolizumab (Keytruda) aims to confirm positive efficacy and safety results previously reported with the combination in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).¹

According to Matthew Matasar, MD, preliminary data supports the use of immunotherapy maveropepimut-s as treatment for patients with relapsed DLBCL.

“This is a pivotal clinical trial that we have developed to attempt to better define the role for a novel immunotherapy and the treatment of patients with multiple relapses to diffuse large B-cell lymphoma,” said Matasar, regional care network medical site director at Memorial Sloan Kettering Cancer Center’s MSK Bergen site, in an interview with Targeted Oncology^TM.

This open-label, randomized phase 2b trial aims to evaluate maveropepimut-S and pembrolizumab with or without low dose, intermittent cyclophosphamide to assess its safety and efficacy in relapsed or refractory DLBCL. Up to 102 eligible subjects will be enrolled across 65 global study sites.²

Enrollment is open to patients with relapsed or refractory, persistent, or progressive DLBCL following 2 or more lines of prior systemic therapy. Patients must be ineligible for or have relapsed after, autologous stem cell transplant and/or chimeric antigen receptor (CAR)-T, have an ECOG performance status of 0 or 1, and a life expectancy of greater than 3 months.

Patients will be randomized 1:1 to either arm 1 or arm 2. In arm 1, patients will be given 2 doses of maveropepimut-S at 0.5 mL 3 weeks apart followed by up to 12 doses at 0.1 mL 8 weeks apart, pembrolizumab 200 mg on the first day of every 3-week cycle, and cyclophosphamide at a self-administered 50 mg dose once a week for 7 days on and 7 days off starting on day 0. In arm 2, patients will be given the same regimen without cyclophosphamide. Patients will be treated for up to 2 years.

The primary end point of the study is centrally assessed overall response rate with secondary end points including profession-free survival, duration of response, overall survival, and safety.

In an interview with Targeted Oncology^TM, Matasar discusses background information on the ongoing VITALIZE trial of maveropepimut-S in patients with DLBCL.

Targeted Oncology: Can you provide a brief overview of what you presented at ASCO this year?

Matasar: It was my pleasure to present on behalf of my colleagues, our ongoing trial in progress by the title of VITALIZE. This is a pivotal clinical trial that we have developed to attempt to better define the role for novel immunotherapy and the treatment of patients with multiple relapses to diffuse large B-cell lymphoma.

What was the basis of this trial?

We have preliminary data that the use of the immunotherapy maveropepimut-S in the treatment of patients with relapsed diffuse large B-cell lymphoma can be active as well as well tolerated. This has been explored in previous clinical trials. The exact best approach to using this medicine and the optimal therapeutic strategy leverages activity is still yet to be fully defined. In that context, the VITALIZE trial is an attempt to clarify the best approach to using this medicine to both improve outcomes and prolong life in patients with multiple relapse DLBCL.

Can you discuss the trial design of VITALIZE?

We know that the study drug maveropepimut-S in combination with pembrolizumab does have clear activity. Previous trials have also used this doublet in combination with low-dose oral cyclophosphamide as an additional immunoadjuvant, not so much as a cytotoxic agent.

The relative contribution of the triplet vs study drug plus pembrolizumab has never been fully understood by the investigators. This is a trial that is designed to clarify the relative contribution of triplet vs doublet therapy in patients with multi-relapse large cell lymphoma.

What were some characteristics of the patients enrolled in the trial?

The study enrollment is ongoing. This is very much a trial in progress. It's a trial that's being conducted globally in the treatment of patients with multiple relapsed diffuse large B-cell lymphomas and this is for patients who have received 2 or more previous lines of therapy in the treatment of diffuse large B-cell lymphoma. Patients eligible for this study must not currently be eligible for autologous stem cell transplant or for CAR T-cell therapy as we believe that that offers people with curative potential. What that means is that this is for patients who have received such treatments in the past and their disease has subsequently relapsed, or they are ineligible for such treatments due to age or comorbidities.

Can you explain the mechanism of action of this agent?

The study drug is a very promising immunotherapeutic agent that could best be thought of in colloquial terms as a survivin vaccine. Survivin is a peptide that is commonly expressed in patients with diffuse large B-cell lymphoma, all the more so in patients with relapsed or refractory disease. The expression of survivin is relatively specific, meaning that it's not widely expressed in normal healthy tissues.

The study drug introduces 5 peptides that are specific to survivin along with immunoadjuvants to stimulate immune response. The injection is given almost as a vaccine and we expect and know that there is uptake in dendritic cells and antigen-presenting cells leading to an immune response against survivin and thus an immunopotentiation effect, where we can induce an immune response against survivin expressing cells, namely diffuse large B-cell lymphoma.

What were the primary and secondary objectives of the study?

The primary objective of the study is to evaluate overall response rate of patients with multiple relapsed large B-cell lymphoma and then to do some work to compare the relative impact of doublet vs triplet immunotherapy in this context.

Response is an important outcome in patients with multiple relapsed large B-cell lymphoma. We know that the ability to achieve response is closely related to anticipated overall survival in this very high-risk patient population. There are some settings where complete response rate is a more appropriate end point, but we believe that in this context, the ability to have a disease response, even a sustained partial response, can lead to improved outcomes that matter in terms of duration of life and quality of life. Thus, overall response rate was selected as our primary end point.

What would you say are the key takeaways of the VITALIZE trial for oncologists?

The key takeaway is that we are now more than ever prepared in the field of diffuse large B-cell lymphoma management andto leverage immunotherapy in the treatment of patients with relapsed or refractory large B-cell lymphoma. CAR T-cell therapy is a well recognized example of such effects. Certainly, CAR T-cell therapy has revolutionized this field to a degree.

We know, however, that most patients will not be cured by CAR T-cell therapy. In some ways, it should be seen more as a proof of principle that immunotherapy can be leveraged when cytotoxic therapies have failed us.

I believe that we need both more effective and less toxic immunotherapies in the treatment of these patients. A vaccination approach such as that which we're exploring in VITALIZE offers tremendous hope and promise to our patients with high-risk relapsed or refractory large B-cell lymphoma.

What are you most excited to see for the future of this space?

I believe in the ability of immunotherapy to revolutionize the care of my patients with relapsed large B-cell lymphoma. Five years ago, all we had was cytotoxic chemotherapy, autologous stem cell transplant, occasionally an allogeneic stem cell transplant, but unfortunately, most patients would succumb to the disease relatively quickly despite our best efforts.

We find ourselves coming into a new era of immunotherapy in this space. Treatments such as maveropepimut-S, which offer the hope of highly effective and relatively well tolerated immunotherapeutic interventions, give me hope for a future in which we can do much better for patients.

References:

1. Matasar M, Teti J, Mody K, et al. VITALIZE: A phase IIb, open-label, multicenter, randomized parallel-group, two-stage, study of maveropepimut-S, pembrolizumab, with or without intermittent low-dose cyclophosphamide, in r/r DLBCL. Annals of Oncology. 2022;33 (suppl 7):646TiP. doi:10.1016/annonc/annonc1055

2. DPX-Survivac and pembrolizumab with and without intermittent low-dose cyclophosphamide, in subjects with relapsed/refractory diffuse large b-cell lymphoma (VITALIZE). ClinicalTrials.gov. Updated August 30, 2022. Accessed September 15, 2022. https://bit.ly/3Fvi78K