maveropepimut-S (MVP-S)

SPiReL is a phase II clinical trial evaluating combination immunotherapy, pembrolizumab and cyclophosphamide, with maveropepimut-S, in survivin-expressing relapsed/refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL). High intensity survivin expression is associated with aggressive clinical features supporting a pathobiological role in R/R DLBCL. Future prognostic models incorporating survivin as a clinical biomarker require assessment of intensity, overall expression and should include potential threshold effects of survivin in DLBCL pathobiology.

P1, N=6, Active, not recruiting, Providence Health & Services | Trial primary completion date: Nov 2023 --> Jun 2023

P2, N=47, Active, not recruiting, University Health Network, Toronto | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

Introduction: The SPiReL phase II clinical trial evaluated combination immunotherapy with an immunogenic vaccine formulation to the tumor antigen survivin comprised of maveropepimut-S (MVP-S), pembrolizumab and cyclophosphamide in survivin-expressing relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL). The mean and median percentage of survivin-positive tumor cells for all enrolled participants (n= 25) was 91% and 99%, respectively. At the per participant level, the range of survivin expression was 50-100% of the cellular content. The heterogeneity of survivin expression intensity among participants is shown in Figure 1.

P1, N=6, Active, not recruiting, Providence Health & Services | Recruiting --> Active, not recruiting | N=18 --> 6 | Trial completion date: Jun 2026 --> Sep 2026 | Trial primary completion date: Jun 2023 --> Sep 2023

P2, N=25, Completed, Sunnybrook Health Sciences Centre | Active, not recruiting --> Completed

This immunotherapy combination was found to be active and safe in this clinically challenging patient population.

P2, N=47, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | Trial primary completion date: Feb 2023 --> Dec 2023

MVP-S with intermittent low-dose CPA is well-tolerated, with clinical benefit for patients with recurrent OvCa. Observed responses are irrespective of the platinum status.

These data indicate that treatment of advanced recurrent ovarian cancer patients with MVP-S based therapy induced robust, persistent survivin-specific T cells that were detected in circulation up to 420 days. These de novo elicited T cells were demonstrated to migrate into tumor tissues, where MVP-S therapy promoted reinvigoration of the total T cell population with new highly diverse clones including strong expansion of survivin-specific T cells.

As of now, 21 sites are actively recruiting in US, Canada, Australia, New-Zealand, and France. Enrollment has begun.

P2, N=25, Active, not recruiting, Sunnybrook Health Sciences Centre | Trial completion date: Oct 2022 --> Oct 2023

Treatment with MVP-S and intermittent, low-dose cyclophosphamide (CPA) has shown to increase tumor infiltration of survivin-specific T cells. Accrual: 3 of 6 patients in the MVP-S+ letrozole arm have been enrolled. Arm B and C will enroll after completion of arm A.

The data herein show that the treatment of advanced metastatic bladder cancer with MVP-S plus CPA in combination with pembrolizumab elicits a strong survivin-specific immune cell response in addition to the clinical response as reported previously (AACR 2022). Taken together, the translational data demonstrate that this novel immune oncology approach leads to immune education that is correlated with improved disease control.

P2, N=102, Ongoing, IMV Inc.

Enrollment has begun, with one subject enrolled as of abstract submission date. Results Trial in progress Conclusion Trial in progress

NCT04895761 is phase I trial evaluating the safety and immunologic effects of neoadjuvant MVP-S plus letrozole (arm A, n = 6), with/without tumor-directed MR-guided radiotherapy (arm B, n = 6), or intermittent low-dose cyclophosphamide or CPA (arm C, n = 6). Biomarker objectives are to evaluate for each treatment arm: 1) systemic type I survivin-specific immune response, as measured by IFN-γ ELISPOT; 2) changes in immune environment by GeoMx digital spatial genomic profiling; 3) and changes in tumor infiltrating lymphocytes (TILs) and Ki67. These data will be used to identify the most immunogenic MVP-S combination therapy for study in phase II trial powered to assess clinical outcome (pCR).

P2, N=184, Active, not recruiting, ImmunoVaccine Technologies, Inc. (IMV Inc.) | Recruiting --> Active, not recruiting

P2b, N=102, Recruiting, ImmunoVaccine Technologies, Inc. (IMV Inc.) | N=152 --> 102

P1, N=18, Recruiting, Providence Health & Services | Not yet recruiting --> Recruiting | Initiation date: Jun 2021 --> Sep 2021

P2, N=25, Active, not recruiting, Sunnybrook Health Sciences Centre | Trial completion date: Apr 2022 --> Oct 2022 | Trial primary completion date: Apr 2021 --> Oct 2021

P2b, N=152, Recruiting, ImmunoVaccine Technologies, Inc. (IMV Inc.) | Not yet recruiting --> Recruiting

P2b, N=152, Not yet recruiting, ImmunoVaccine Technologies, Inc. (IMV Inc.)

P1, N=18, Not yet recruiting, Providence Health & Services

P2, N=25, Active, not recruiting, Sunnybrook Health Sciences Centre | Recruiting --> Active, not recruiting

P2, N=184, Recruiting, ImmunoVaccine Technologies, Inc. (IMV Inc.) | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Dec 2023

The primary endpoint of this study has been reached with 7/11 (63.6%) of evaluable subjects achieving an objective response warranting further exploration of DPX-Survivac in this population. Enrollment is continuing to further define the patient population most likely to benefit from this well-tolerated therapy.

P2, N=25, Recruiting, Sunnybrook Health Sciences Centre | Trial completion date: May 2021 --> Apr 2022 | Trial primary completion date: May 2020 --> Apr 2021

DPX-Survivac combination immunotherapy induces the recruitment of CD8+ T cells into tumors, resulting in tumor control in an orthotopic ovarian cancel model.

DPXSurvivac/CPA with pembrolizumab is well tolerated and shows early signs of clinical efficacy and disease control in advanced and metastatic solid tumors. Research Sponsor: IMV Inc.

DPX-Survivac and intermittent low dose CPA shows promising clinical activity in heavily pre-treated patients with recurrent OvCa. The preliminary results, supported by strong translational data, link the observed clinical benefits with the unique MOA of DPX-Survivac. These clinical results suggest that DPX-Survivac/CPA is an active regimen in OvCa and warrant testing in an expanded cohort of patients.

DPX-Survivac stimulates significant clinical anti-tumor responses by inducing strong and sustained survivin-specific T cell responses and increasing infiltration of target-specific T cells into tumors. Clinical trial information: NCT01416038; NCT03332576; NCT02785250. Research Funding: IMV Inc., Pharmaceutical/Biotech Company.

DPX-Survivac stimulates significant clinical anti-tumor responses by inducing strong and sustained survivin-specific T cell responses and increasing infiltration of target-specific T cells into tumors. Clinical trial information: NCT01416038; NCT03332576; NCT02785250. Research Funding: IMV Inc., Pharmaceutical/Biotech Company.

At the time of data cut-off, 23 subjects have been screened and 12 have been enrolled. The demographics of enrolled subjects include: median age is 75.5 years (50-82), with 3 male subjects participating. The median number of prior therapies is 2.5 (1-6), with 4 subjects having previously undergone ASCT.