Following feedback from the FDA, IMV Inc. and Merck have entered into an agreement to open a phase 2b clinical trial examining the combination of maveropepimut-S and pembrolizumab plus low-dose cyclophosphamide in patients with recurrent/refractory diffuse large B-cell lymphoma.
Following feedback from the FDA, IMV Inc. and Merck have entered into an agreement to open a phase 2b clinical trial examining the combination of maveropepimut-S (DPX-Survivac) and pembrolizumab (Keytruda) plus low-dose cyclophosphamide in patients with recurrent/refractory diffuse large B-cell lymphoma (DLBCL).1
The phase 2b trial will be a 3-arm, randomized, parallel-group, Simon 2-stage study. The combination of DPX-Survivac and pembrolizumab will be evaluated with or without cyclophosphamide, and a third arm will examine DPX-Survivac monotherapy. Investigators are expected to enroll up to 150 patients, all of whom have received 2 or more prior lines of systemic therapy, and who are ineligible for, or have failed, chimeric antigen receptor T-cell therapy or autologous stem cell transplant.
The primary end point will be overall response rate (ORR); additionally, patients will be evaluated for baseline PD-L1 expression to validate it as a possible predictive biomarker for the combination regimen. This is based on data from the phase 2 SPiReL trial (NCT03349450), which evaluated the combination of DPX-Survivac with pembrolizumab and cyclophosphamide.
“We are proud to continue working with Merck to deepen the relationship that was built during our basket trial and the prior SPiReL study in [relapsed/refractory] DLBCL,” said Andrew Hall, chief business officer at IMV. “This new agreement continues to leverage our common vision to save and improve lives by delivering better treatments to patients with unmet medical needs. In this collaboration we look forward to collaborating with Merck, beyond the provision of Keytruda, to ensure clinical and regulatory alignment, thus optimizing our probability of success.”
DPX-Survivac is described as a new class of immunotherapy that generates targeted and has sustained cancer cell killing capabilities in vivo. As a maintenance treatment for patients with advanced ovarian cancer, the agent has previously received Fast Track designation and Orphan Drug designation from the FDA, as well as Orphan Drug designation from the European Medicines Agency.
Previously, IMV announced that the FDA provided feedback regarding the design of the study, which is expected to begin in the second quarter of 2021.2
Data from the SPiReL trial, which was presented at the 2020 ASH Annual Meeting and Exposition, showed promising clinical activity in patients with recurrent or refractory DLBCL. The combination met its primary endpoint. Additionally, an analysis of 7 patients with PD-L1 expression demonstrated a higher median progression-free survival of 230 days compared with 70 days for those who were PD-L1 negative (P = .007). Moreover, patients who had PD-L1–positive disease had an ORR and disease control rate (DCR) of 85.7%.2-4
Additionally, the combination of DPX-Survivac and cyclophosphamide was previously examined in the phase 2 DeCidE1 trial (NCT02785250), and showed prolonged clinical benefit and promising tolerability in patients with advanced recurrent ovarian cancer. According to topline data presented in December 2020, 78.9% of evaluable patients (n = 15/19) demonstrated disease control, 37% of patients (n = 7/19) achieved partial response (PR) or stable disease (SD) lasting more than 6 months, and 26% of patients (n = 5/19) achieved PR or SD lasting more than 1 yeat Moreover, treatment with DPX-Survivac and cyclophosphamide was well tolerated, with most reported adverse effects being grades 1 or 2.
“The guidance from the FDA is an important milestone for the company and we believe it provides us regulatory clarity and confidence to advance our development strategy for our lead immunotherapy in this difficult-to-treat patient population,” stated Frederic Ors, chief executive officer at IMV. “We intend to initiate this trial rapidly and will seek to confirm the promising results obtained in the SPiReL study.”