CVT-DC-01 / Medigene - LARVOL DELTA

WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy. (PubMed, Leukemia) - "Oral azacytidine may be used as maintenance treatment in AML in first remission, but can be associated with substantial side effects, and less toxic strategies should be explored. OS at five years was 75% (95% CI: 50-89), with 70% of patients ≥60 years of age being long-term survivors. Maintenance therapy with this DC vaccine was well tolerated in AML patients in CR1 and was accompanied by encouraging 5-year long-term survival."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • PRAME

[VIRTUAL] Consistent high-quality dendritic cell vaccines produced post-chemotherapy in patients with acute myeloid leukemia for use in a Phase I/II trial (SITC 2020) - P1/2 | "DC vaccination was carried out in weeks 1, 2, 3, 4, 6 and monthly thereafter for 2 years. DC vaccines were remarkably consistent, although originating from patients differing in age, AML subtype and receiving varied amounts of standard chemotherapy regimens. Ethics Approval The study was approved by the responsible Norwegian ethics committee, approval number 2014/1677."

Clinical • IO Biomarker • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL10 • IL12A • PRAME

[VIRTUAL] Consistent high-quality dendritic cell vaccines produced post-chemotherapy in patients with acute myeloid leukemia for use in a Phase I/II trial (SITC 2020) - P1/2 | "DC vaccination was carried out in weeks 1, 2, 3, 4, 6 and monthly thereafter for 2 years. DC vaccines were remarkably consistent, although originating from patients differing in age, AML subtype and receiving varied amounts of standard chemotherapy regimens. Ethics Approval The study was approved by the responsible Norwegian ethics committee, approval number 2014/1677."

Clinical • IO Biomarker • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IL10 • IL12A • PRAME

Immune Monitoring of Vaccine Quality and Persistence of Specific T Cell Responses in Five AML Patients Receiving Extended Dendritic Cell Vaccination Under Compassionate Use (ASH 2018) - P1/2; "To replace SCT in non-eligible patients, we designed an autologous dendritic cell (DC) vaccine approach that is given 4 times weekly at the beginning (immunization phase) followed by booster vaccines at week six and then monthly, with the intention to induce immune responses that delay or prevent relapse. The fifth patient was vaccinated for 24 months without signs of relapse but died due to unrelated heart disease. The ongoing clinical study using extended DC vaccination will provide more information whether persistent vaccination against these self-antigens contributes to immune responses that prevent disease relapse in AML patients."

Clinical • PD(L)-1 Biomarker • Acute Myelogenous Leukemia • Biosimilar • Cardiovascular • Heart Failure • Immune Modulation • Inflammation • Leukemia • Melanoma • Oncology • Renal Cell Carcinoma • Transplantation

INTERIM ANALYSIS OF A WT-1 AND PRAME ‘FAST-DC’ VACCINE SHOWS SAFETY AS ACTIVE IMMMUNOTHERAPY FOR THE PREVENTION OF AML RELAPSE (EHA 2019) - P1/2; "AML diagnoses were established with a median of 9.8 months before the first vaccination (range 4.5 to 17.5 months), and the last chemotherapy infusion was performed at a median of 6.9 months (range 2 to 14.8 months).Results The manufacture of the DC vaccine in these chemotherapy-pretreated subjects was feasible for all 20 patients and aliquots of 5 to 10 x 106 cells were used per vaccination. After a 12-months treatment period, the overall survival was 89% (18 of 20 patients, 95% confidence interval: 61 to 97%) and the progression free survival was 60% (12 of 20 patients, 95% confidence interval: 36 to 78%). Most relapses, 5 out of 8, occurred within the first 80 days after the start of the vaccination, out of which the 2 deaths were in patients with relapses on days 45 and 64, which could point to a starting relapse upon entering the study.Conclusion In summary, at a follow up time of 1 year, DC vaccination against WT-1 and PRAME appears to be safe and feasible for use..."

Clinical

Medigene AG: Detailed analysis from Medigene's completed Phase I/II DC vaccine in AML patients presented orally at ASH 2020 (PharmiWeb) - P1/2, N=20; NCT02405338; Sponsor: Medigene AG; "Medigene AG..is excited to announce that an oral presentation of results from the Phase I/II clinical trial of its dendritic cell (DC) vaccine in acute myeloid leukemia (AML) patients was given by the study's Principal Investigator Dr. Yngvar Floisand at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition on Saturday, 5 December 2020... The previously reported topline results showed an excellent safety and feasibility profile and encouraging overall survival (OS: 80% at 2 years, including patients over 60 years of age) and progression free survival (PFS: 55% at 2 years)."

P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

POSITIVE PHASE I/II TRIAL FEASIBILITY RESULTS - CONSISTENT HIGH-QUALITY DC VACCINES IN AML PATIENTS (MediGene Press Release) - P1/2, N=20; NCT02405338; Sponsor: Medigene; "Medigene AG...is pleased to present production feasibility results from the dendritic cell (DC) vaccine Phase I/II clinical trial completed earlier this year in a poster at the Society for Immunotherapy of Cancer 35th Annual Meeting (SITC 2020) being held virtually on 9-14 November 2020. The poster # 271 will be available in the Virtual Poster Hall from 11-14 November 2020 from 9:00 am - 5:00 pm EST (3:00 pm - 11:00 pm CET), Q&A sessions will be held on Wednesday, 11 November 2020, 5:15 pm - 5:45 pm EST (11:15 pm - 11:45 pm CET) and on Friday, 13 November 2020, 4:40 pm - 5:10 pm EST (10:40 pm - 11:10 pm CET)."

P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

DC Vaccination for Post-remission Therapy in AML (clinicaltrials.gov) - P1/2; N=20; Completed; Sponsor: Medigene AG; Active, not recruiting ➔ Completed; Trial completion date: Dec 2020 ➔ Nov 2019

Clinical • Trial completion • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • PRAME

Positive final 2-year topline data in completed DC vaccine phase I/II trial in AML patients (GlobeNewswire) - P1/2, N=20; NCT02405338; Sponsor: Medigene AG; "The trial’s primary outcome measures assessing 1) the feasibility of DC vaccine manufacturing/administration, and 2) its safety/tolerability over 2 years, were successfully achieved. The secondary outcome measures evaluating key clinical parameters show that after 24 months of treatment overall survival rate (OS) was 80% (16 of 20 patients, 95% confidence interval (CI): 55 to 92%) and progression free survival rate (PFS) was 55% (11 of 20 patients, 95% CI: 31 to 74%)...Patients 60 years of age or olde...accounted for 50% of patients in this trial (risk groups good, intermediate, poor: 4, 4, 2) and an excellent OS of 80% (8 of 10 patients, 95% CI: 41 to 95%) and a PFS of 50% (5 of 10 patients, 95% CI: 18 to 75%) was observed at 24 months."

P1/2 data

DC Vaccination Induces Antigen Specific Immune Responses in AML Patients: A 1-Year Interim Assessment (ASH 2019) - "Based on expression profiles in AML and normal tissues, WT1 and PRAME were selected as target antigens for a DC vaccine, aiming to elicit adaptive and innate immune responses in AML patients. Stable or decreasing levels of WT1 and/or PRAME mRNA in bone marrow of most patients in remission is compatible with the hypothesis that a local response against AML antigens may be ongoing, despite a negative IFN-γ response in peripheral blood. Monitoring of the patients currently in remission may shed some light on the role of DC vaccination on the prevention of AML recurrence."

Clinical • IO Biomarker • IFNG • IL10 • IL12A

Medigene AG: Interim 1-year clinical immune monitoring data from DC vaccine trial in AML presented at ASH 2019 Annual Meeting (MediGene Press Release) - P1/2, N=20; NCT02405338; Sponsor: Medigene AG; “The vaccinations were well tolerated with no serious adverse events (SAEs) related to the treatment. The most common adverse events (AEs) were injection site related, accounting for 35% of all AEs and mild in nature (Grade 1). After a 12-month treatment period, the overall survival was 89% (18 of 20 patients, 95% confidence interval: 61 to 97%) and the progression free survival was 60% (12 of 20 patients, 95% confidence interval: 36 to 78%). Most relapses, 5 out of 8, occurred within the first 80 days after initiation of vaccination, suggesting a possible molecular relapse upon entering the study.”

P1/2 data

Interim analysis from ongoing phase I/II clinical trial with DC vaccines in AML patients presented at EHA (MediGene Press Release) - P1/2, N=20; NCT02405338; Sponsor: Medigene AG; “AML diagnoses had been established with a median of 9.8 months before the first vaccination (range 4.5 to 17.5 months), and the last chemotherapy infusion had been performed at a median of 6.9 months (range 2 to 14.8 months)….The vaccinations were well tolerated with no serious adverse events (SAEs) related to the treatment. The most common adverse events (AEs) were injection site related, accounting for 35% of all AEs and mild in nature (Grade 1).After a 12-months treatment period, the overall survival was 89% (18 of 20 patients, 95% confi-dence interval: 61 to 97%) and the progression free survival was 60% (12 of 20 patients, 95% confidence interval: 36 to 78%). Most relapses, 5 out of 8, occurred within the first 80 days after initiation of vaccination, suggesting a possible molecular relapse upon entering the study.”

P1/2 data