Preliminary VITALIZE Results Show CRs to IO Combination in R/R DLBCL

An investigational immunotherapy, maveropepimut-S (MVP-S; DPX-Survivac), combined with pembrolizumab (Keytruda) showed promising efficacy in preliminary results from the phase 2b VITALIZE trial (NCT04920617) of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), reported by IMV Inc.¹

In the VITALIZE trial, 3 out of 6 evaluable patients showed clinical complete responses, with 1 other showing stable disease and 2 with progressive disease.

"VITALIZE is our most advanced and rigorous trial to date, and we are encouraged by the way the data for MVP-S are trending. This is the most refractory population of patients we have treated so far, and to show complete, confirmed clinical responses is notable,” Andrew Hall, MSc, CEO of IMV, said in a press release.

The novel immunotherapy, given as a subcutaneous injection, offers a different mechanism of action based on inducing an immune response to the cancer antigen survivin, which is expressed in DLBCL cells.

The VITALIZE trial is a randomized Simon 2-stage study assessing MVP-S plus pembrolizumab in 2 arms, with arm 1 also including intermittent low-dose cyclophosphamide. Patients must have received at least 2 prior lines of therapy and must be ineligible or progressed after autologous stem cell transplant or chimeric antigen receptor therapy. The first stage is planned to enroll 15 patients in each arm, with an option to expand to up to 102 total patients in the second stage.

Patients in the trial will receive injections of MVP-S on day 7 and day 28, then additional doses every 8 weeks. Pembrolizumab is given at 200 mg every 3 weeks and, in arm 1, 50 mg cyclophosphamide is given twice daily every other week. The primary end point is overall response rate (ORR), with secondary end points including safety, duration of response, and progression-free survival.

Eight patients with an ECOG performance score of 0 or 1 were enrolled in arm 1. Six of these patients were evaluable for responses. Two patients were not evaluable due to poor baseline functionality (ECOG performance score of 2 or greater) and did not stay on the study until the first scan. ORR will be announced when all data on stage 1 patients are available.

There were no adverse safety signals associated with MVP-S, which was consistent with previous clinical trials. In the prior phase 2 SPiReL trial (NCT03349450) of patients with R/R DLBCL who received MVP-S, pembrolizumab, and cyclophosphamide, only 11% of treatment-related adverse events (TRAEs) were grade 3 or higher, and the majority of grade 1 and 2 TRAEs were injection-site reactions to MVP-S.²

MVP-S is also being investigated with low-dose cyclophosphamide in patients with platinum-resistant ovarian cancer in the ongoing single-arm phase 2b AVALON trial (NCT05243524).¹ This trial also has 2 stages, and investigators plan to enroll 41 patients in the first stage and expand to up to 73 patients.

Additionally, it is being investigated a phase 2 trial (NCT03836352) in combination with pembrolizumab and cyclophosphamide in patients with ovarian cancer, hepatocellular carcinoma, non–small cell lung cancer, urothelial cancer, and microsatellite instability–high tumors. A phase 1 trial (NCT04895761) began in 2021 to investigate MVP-S alone, with an aromatase inhibitor, or with radiation therapy as neoadjuvant therapy for patients with hormone receptor–positive, HER2-negative breast cancer.

“These positive initial results, combined with the accelerating recruitment of the AVALON study in platinum resistant ovarian cancer add, we believe, to the growing industry enthusiasm about the potential for MVP-S in multiple tumor settings,” Hall stated in the press release.

_References:

_{1. IMV Inc. presents positive initial results from the MVP-S phase 2B VITALIZE trial. IMV Inc. February 13, 2023. Accessed February 14, 2023. https://bit.ly/3xkyCTs}

_{2. Berinstein NL, Bence-Buckler I, Forward NA, et al. Clinical effectiveness of combination immunotherapy DPX-Survivac, low dose cyclophosphamide, and pembrolizumab in recurrent/refractory DLBCL: the SPiRel study. Blood. 2020;136(suppl_1):16. doi:10.1182/blood-2020-136751}