IMV’s DPX-Survivac promotes anti-cancer responses and boosts the sensitivity of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) to Keytruda (pembrolizumab) combined with chemotherapy, interim data from a Phase 2 study show.
In the trial, three of nine patients attained complete responses to treatment, two had partial responses, and two experienced disease stabilization. In total, this represented a clinical benefit of 77.8%.
“In contrast, both to standard-of-care treatments and other immunotherapeutic approaches in development, to observe this clinical benefit alongside a favorable safety profile highlights DPX-Survivac’s potential to reach this patient population in dire need of better treatment options,” Neil Berinstein, MD, the trial’s lead investigator and a hematologist at Sunnybrook Health Sciences Centre, in Toronto, Canada, said in a press release.
The results were presented by Berinstein in a poster, “Combination of DPX-Survivac, Low Dose Cyclophosphamide, and Pembrolizumab in Recurrent/Refractory DLBCL: The SPiReL Study,” at the 61st American Society of Hematology (ASH) Annual Meeting, held in Orlando, Florida.
DPX-Survivac is a cancer vaccine that helps the immune system target cancer cells producing survivin, a protein found in 60% of DLBCL cases and associated with tumor progression and treatment resistance.
This vaccine was shown to boost the recruitment of T-cells within tumors, increasing PD-L1 levels in cancer cells and, thus, making tumors more sensitive to immune checkpoint inhibitors, such as Keytruda.
Marketed by Merck (known as MSD outside the U.S. and Canada), Keytruda prevents the interaction between the PD-1 receptor on immune T-cells and its ligand PD-L1 in cancer cells — a mechanism often used by cancer cells to evade anti-tumor immune responses. By preventing this interaction, Keytruda boosts the ability of T-cells to detect and fight tumor cells.
The SPiReL Phase 2 trial (NCT03349450) is evaluating the safety and effectiveness of DPX-Survivac, in combination with low-dose cyclophosphamide chemotherapy and Keytruda, in up to 25 relapsed or refractory DLBCL patients whose tumors are positive for survivin. The trial is being sponsored by the Sunnybrook Health Sciences Centre.
Participants, recruited at five clinical sites in Canada, receive two 0.5 mL shots of DPX-Survivac, three weeks apart (followed by up to six 0.1 mL doses every eight weeks), along with twice-daily oral cyclophosphamide (on alternating weeks), and Keytruda injections every three weeks for up to one year or until disease progression. Patients may receive six additional booster vaccinations during the trial.
SPiReL’s primary goal is to determine the patients’ response rate, while secondary goals include duration of response and safety. Investigators will also assess T-cell response and infiltration within the tumor, as well as potential biomarkers of immune and clinical response as exploratory measures.
The study has enrolled 17 patients (11 women and six men), as of Dec. 1, 2019. Participants, with a median age of 75 years, had received a median of two prior treatments (range from one to six).
Results showed that seven patients progressed too fast to receive treatment and be evaluated. Seven out of nine patients (77.8%) with evaluable data showed reduced or stable disease. One patient reached a complete response at the first evaluation following treatment and showed no signs of disease relapse after completing the study.
Survivin-specific T-cell responses were observed in 53% of participants (eight of 15 patients analyzed), including all seven patients who showed a clinical response.
“These data further validate DPX-Survivac’s novel mechanism, extending previously documented results in solid cancers now to survivin-expressing [blood cancers], and support the hypothesis that our lead candidate works well in combination with checkpoint inhibitors,” said Joanne Schindler, MD, IMV’s chief medical officer.
The triple combo was well-tolerated and showed a manageable safety profile, with mild to moderate injection-site reactions as the most common adverse events and few severe to life-threatening adverse events. There were no treatment discontinuations related to side effects.
“Treatment of recurrent/refractory patients with DLBCL is feasible with a very favorable toxicity profile that is well suited for all patients, including older patients, or those with comorbidities [additional conditions],” the researchers wrote in the poster.
Schindler added that the company believes DPX-Survivac’s combo represents “a potentially meaningful alternative to more toxic chemotherapy regimens,” and is planning to launch a clinical study of the combo in relapsed or refractory DLBCL patients this year.
Of note, the current study has disclosed that Berinstein and another researcher have links to Merck.
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