February 13, 2023

Kristi Rosa

The combination of maveropepimut-S, pembrolizumab, and intermittent low-dose cyclophosphamide elicited responses in patients with relapsed or refractory diffuse large B-cell lymphoma, according to preliminary findings from the phase 2b VITALIZE trial.

The combination of maveropepimut-S (MVP-S; DPX-Survivac), pembrolizumab (Keytruda), and intermittent low-dose cyclophosphamide elicited responses in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to preliminary findings from the phase 2b VITALIZE trial (NCT04920617).¹

Data showed that of 6 evaluable patients enrolled to arm 1, 3 had confirmed complete responses to the regimen. Moreover, 1 patient was assessed to have stable disease as their best response to treatment, and 2 patients experienced disease progression.

When all the stage I data are available for definitive evaluation, overall response rate (ORR) will be shared, according to a press release issued by IMV Inc.

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

It is known that survivin has an important role in tumor biology because it is linked with tumor cell differentiation, proliferation, invasion, and metastasis. It is hypothesized that the agent can provide continued flow of survivin-targeted T cells expressed on tumor cells, which could result in clinical efficacy. Previously, the agent has been found to elicit strong, sustained, antigen-specific immune response, as well as an acceptable toxicity profile.²

The randomized, parallel-group, Simon 2-stage study was launched to evaluate MVP-S plus pembrolizumab with (arm 1) or without (arm 2) cyclophosphamide.³

To be eligible for enrollment, patients were required to have a pathologically confirmed diagnosis of DLBCL with at least 1 measurable lesion per Lugano criteria; they also needed to be at least 18 years of age, have an ECOG performance status of 0 or 1, and have experienced disease progression after at least 2 previous lines of systemic treatment. Moreover, patients needed to have had autologous stem cell transplant (ASCT) or CAR T-cell therapy fail or have been ineligible to receive those approaches.³

If patients had primary central nervous system (CNS) lymphoma or active secondary CNS involvement and/or lymphomatous meningitis, they were excluded. Patients also could not have received radiotherapy within 2 weeks, ASCT within 100 days, or CAR T-cell therapy within 28 days of day 0.3

For arm 1, patients were given two 0.5-mL doses of MVP-S every 3 weeks and then up to twelve 0.1-mL doses every 8 weeks. Pembrolizumab was given at a flat dose of 200 mg on the first day of every 3-week cycle. Cyclophosphamide was self-administered at a twice daily dose of 50 mg on a 7-days-on/7-days-off scheduled starting on day 0.3

ORR in each of the study arms is the primary outcome measure of the trial. Key secondary outcome measures include rate of toxicities, duration of response, time to response, progression-free survival, disease control rate, complete response rate, and patient-reported outcome assessments.³

Other outcome measures of interest include ORR based on PD-L1 expression, time to next treatment, overall survival, time to second objective disease progression, cell-mediated immune response, and changes in immune cell infiltration in biopsies.³

The combination is slated to be examined in up to 30 patients in stage 1 of the trial (2 arms of 15 patients) with the option to expand to up to 102 total patients in stage 2.¹

“These positive initial results, combined with the accelerating recruitment of the AVALON study [NCT05243524] in platinum-resistant ovarian cancer add, we believe, to the growing industry enthusiasm about the potential for MPV-S in multiple tumor settings,” Hall added.¹

In the open-label, company-sponsored, single-arm, phase 2b AVALON trial, investigators are examining the safety and efficacy of MVP-S and intermittent low-dose cyclophosphamide in patients with platinum-resistant ovarian cancer.⁴

The research leverages a Simon 2-stage design; stage 1 will include up to 41 patients, with the option to expand to 73 total patients in stage 2. Participants will be administered 2 doses of MVP-S subcutaneously every 3 weeks, and then MVP-S every 8 weeks, in combination with low-dose oral cyclophosphamide on a repeating cycle of 1-week-on and 1-week-off. The primary outcome measure for this research is ORR by RECIST v1.1 criteria.⁴

References

1.     IMV Inc. presents positive initial results from the MVP-S phase 2b VITALIZE trial. News release. IMV Inc. February 13, 2023. Accessed February 13, 2023. https://www.imv-inc.com/news-events/press-releases

2.     Maveropepimut-s (DPX-Survivac). IMV Inc website. Accessed February 13, 2023. https://www.imv-inc.com/product-pipeline/maveropepimut-S

3.     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 February 13, 2023. Accessed February 13, 2023. https://clinicaltrials.gov/ct2/show/NCT04920617

4.     Maveropepimut-S (MVP-S) and low-dose CPA in patients with platinum-resistant ovarian cancer (AVALON). ClinicalTrials.gov. Updated December 23, 2022. Accessed February 13, 2023. https://clinicaltrials.gov/ct2/show/NCT05243524