DCP-001 Yields MRD Responses Leading to Boosts in Survival in Patients With AML

Interim results of the ADVANCE II study of DCP-001 revealed durable measurable residual disease responses in patients with acute myeloid leukemia.

Interim results of the ADVANCE II study (NCT03697707) of DCP-001 (DCOne) revealed durable measurable residual disease (MRD) responses in patients with acute myeloid leukemia (AML). These data were presented in press conference by Immunicum.

MRD responses were seen in 7 (35%) out of the 20 patients in the study. Stable MRD was observed in 7 patients (35%). Five patients (25%) who were CR1– and MRD–positive became MRD–negative. A 10-fold reduction in MRD was seen in 2 patients (20%). Within 32 weeks after vaccination, 6 patients (30%) relapsed.

ADVANCE II is a multicenter, international, open-label, phase 2 study (NCT03697707) designed to confirm DCP-001 as a novel maintenance therapy for AML treatment. Twenty patients were selected based on MRD–positive status and complete remission. Investigators administered 4 biweekly vaccinations at 25 or 50 million cells per vaccination at weeks 0, 2, 4, and 6. Patients were given 2 booster vaccinations at 10 million cells per vaccination at weeks 14 and 18. The study’s primary end points were the effect DCP-001 had on MRD status, the effect on immune responses in patients with the first CR1 who had persistent MRD, and safety. Secondary end points included relapse-free survival (RFS) and overall survival (OS). ADVANCE II is being conducted across 10 centers in the Netherlands, Germany, Sweden, Norway, and Finland.

Investigators evaluated MRD responses after the 4 initial vaccinations with a median time on study less than 14.3 weeks (range, 14-20). MRD responses were durable in 4 of 5 patients who remained MRD–negative to week 32. The median time between the initiation of DCP-001 therapy and chemotherapy for the whole patient population was 295 days.

MRD responses showed a link to prolonged survival. Both median RFS and median OS were not reached. The estimated probability of RFS at 6 months is 83.7% (range, 64%-94%), and the estimated probability of OS at 6 months is 97.0% (range, 79%-99%). Investigators noted that converted MRD patients stayed relapse-free at follow up.

The median age of patients was 60 years (range, 34-79), and half of the patient population was female. These gene expressions were found among the study group: NPM1 (n = 10), CBFC-MYH11 (n = 4), IDH2 (n = 2), RUNX11-RUNX1T1 (n = 2), FAB-M4 (n = 1), and CEBPA (n = 1). European LeukemiaNet risk scores revealed to be favorable in 13 patients, intermediate in 6, and adverse in 1. All patients had MRD–positive status except for 1 at baseline.

DCP-001 vaccinations did not cause any serious adverse events (AEs). Overall, DCP-001 was well tolerated with manageable AEs found at the injections site. Patients reported inflammation at injection site, pruritis, diarrhea, paresthesia, conjunctivitis, headache, and arthralgia.

“MRD as the primary end point in phase 2 studies is of increasing importance for predicting relapse-free and overall survival,” commented principal study investigator Arjan van de Loosdrecht, MD, PhD. “The ADVANCE II study showed that DCP-001 induces sustained MRD conversion in a subset of patients with AML and hence with prolonged RFS and OS as compared to those who did not achieve MRD conversion. These data confirmed the power of MRD as a primary end point as well as immunotherapeutic potential of DCP-001.” Loosdrecth is principal investigator of ADVANCE II and is the lead scientist in myelodysplastic syndromes and AML at Amsterdam University Medical Center.

Based on these data, ADVANCE II will be expected to develop DCP-001 further. Immunicum will also present additional updates to ADVANCE II in the fourth quarter of 2022, focusing on RFS and OS data as well as immunomonitoring data.

REFERENCE

Interim results from ADVANCE II study of DCP-001 for AML maintenance treatment. Press conference. Immunicum; May 16, 2022. Accessed May 17, 2022. https://edge.media-server.com/mmc/p/ik922ghk