MesoPher (autologous dendritic cell vaccine) / Amphera - LARVOL DELTA

ENSURE: dENdritic Cell Therapy Combined With SURgEry in Mesothelioma (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Erasmus Medical Center | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor

MesoPher Cell Therapy Increases 2-Year RFS Rate in Resected Pancreatic Cancer by 50%; Amphera Announces Publication of Phase II Results in Journal of Clinical Oncology and Orphan Designation Granted by FDA & EMA (Businesswire) - P2 | N=26 | REACTIVE (2018-003222-92) | "Amphera B.V...announces publication of the results of a phase II trial in resected pancreatic cancer (REACTIVE) in the Journal of Clinical Oncology (JCO)....The phase II trial, including 38 patients with resected pancreatic cancer who had completed standard-of-care chemotherapy, met the primary endpoint demonstrating a clinically significant increase in 2-year recurrence-free survival of 64% compared to an expected 40%. This was accompanied with only low grade side effects. The 2-year overall survival rate was 83%. Translational immune-profiling supports an induction of an effective immune-activation against the tumor. Patients in the REACTIVE trial received 3 bi-weekly injections of Amphera’s MesoPher dendritic cell therapy and booster injections at 4 and 7 months."

P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Dendritic cells loaded with allogeneic tumour cell lysate plus best supportive care versus best supportive care alone in patients with pleural mesothelioma as maintenance therapy after chemotherapy (DENIM): a multicentre, open-label, randomised, phase 2/3 study. (PubMed, Lancet Oncol) - P2/3 | "MesoPher did not show improvement in overall survival in patients with pleural mesothelioma. Immune checkpoint therapy is now standard of care in pleural mesothelioma. Further randomised studies are needed of combinations of MesoPher and immune checkpoint therapy, which might increase efficacy without adding major toxicities."

Journal • P2/3 data • Tumor cell • Dermatology • Fatigue • Hematological Disorders • Infectious Disease • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pain • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor

DENIM: DENdritic Cell Immunotherapy for Mesothelioma (clinicaltrials.gov) - P2/3 | N=176 | Completed | Sponsor: Amphera BV | Recruiting ➔ Completed

Trial completion • Mesothelioma • Oncology • Solid Tumor

MesoPher/Mitazalimab-combination Therapy in Metastatic Pancreatic Disease (REACtiVe-2 Trial) (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: Joachim Aerts, MD PhD | Recruiting ➔ Completed | Trial completion date: Oct 2023 ➔ May 2023 | Trial primary completion date: Oct 2023 ➔ May 2023

Combination therapy • IO biomarker • Metastases • Trial completion • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • CD40

Dr Aerts on Results From the DENIM Trial of Dendritic Cell Vaccination in Mesothelioma (OncLive) - P2/3 | N=230 | DENIM (NCT03610360) | Sponsor: Amphera BV | "The phase 3 DENIM trial evaluated the ability of an allogenic dendritic cell vaccine to induce immune responses in patients with mesothelioma when used as maintenance therapy....Results showed that the trial did not meet its primary end point of improved overall survival (OS), Aerts reports, as there was no significant increase in OS with dendritic cell therapy vs BSC alone. The median OS in the dendritic cell arm was 16.9 months (95% CI, 12.4-20.4) compared with vs 18.3 months with BSC alone (HR, 1.10 [0.765-1.572]; 95% CI, 14.3-21.9). Likewise, the median progression-free survival was 166 days (95% CI, 99-178) for the vaccine group and 99 days (95% CI, 93-136) for the BSC group."

P2/3 data • Mesothelioma • Oncology • Solid Tumor

Dendritic Cell Immunotherapy Versus Best Supportive Care as Maintenance Treatment in Patients with Pleural Mesothelioma (IASLC-WCLC 2023) - "The DENIM trial is a randomised phase III study in patients with UPM comparing MesoPher, as a maintenance treatment after completion of first line chemotherapy versus best supportive care (BSC). Eligible patients were non progressing after 4-6 cycles of platinum/pemetrexed. The DENIM study failed to show increased OS with MesoPher. Likely the long interval between chemotherapy and the start of treatment caused that most patients had already disease progression before or during the first 3 DC treatments, prohibiting the induction of an effective immune response. This interval was extended compared to earlier MesoPher studies because randomization and additional sterility tests."

Clinical • IO biomarker • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Sarcoma • Solid Tumor • CD4

Amphera Announces a Positive Opinion of the European Medicines Agency on the Granting of Orphan Medicinal Product Designation for MesoPher in Pancreatic Cancer (Businesswire) - "Amphera B.V....announces that the EMA Committee for Orphan Medicinal Products (COMP) has recommended the granting of orphan medicinal product designation for MesoPher in pancreatic cancer."

European regulatory • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Amphera and Alligator Bioscience reveal mitazalimab-MesoPher update (PharmaTimes) - "Alligator Bioscience and Amphera have announced that the last patient in their REACTIVE-2 phase 1 research has been dosed. The research is evaluating mitazalimab when used in combination with MesoPher among patients with metastatic pancreatic cancer....The REACTIVE-2 study is currently being performed at Erasmus Medical Center in Rotterdam, the Netherlands, while initial results are expected later this year."

Enrollment closed • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

MesoPher/Mitazalimab-combination Therapy in Metastatic Pancreatic Disease (REACtiVe-2 Trial) (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Joachim Aerts, MD PhD

Combination therapy • IO biomarker • New P1 trial • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Immune Modulation • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • CD40

Amphera Announces Clinical Updates of MesoPher Cell Therapy (Businesswire) - P2 | N=38 | "In the phase II Reactive trial, patients with resected pancreatic cancer who had completed standard-of-care chemotherapy received 3 bi-weekly injections of Amphera’s MesoPher dendritic cell therapy and booster injections at 4 and 7 months....The Reactive trial met the primary endpoint with topline safety and efficacy data from two cohorts of in total 38 patients demonstrating a statistically significant 2-year Recurrence Free Survival of 60%....Based on these results, a 2nd cohort of 28 patients was fully enrolled. As established in all MesoPher trials, the safety profile is excellent."

P2 data • Trial status • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Amphera Announces Clinical Updates of MesoPher Cell Therapy (Businesswire) - P2/3 | N= 230 | NCT03610360 | Sponsor: Amphera BV | "In the DENIM trial, mesothelioma patients with stable disease or better after platin-pemetrexed chemotherapy received either MesoPher maintenance treatment or best supportive care (BSC)....The DENIM trial confirmed MesoPher’s excellent safety profile and MesoPher induced a robust T-cell response. The immune response did not translate into clinical benefit, and consequently the primary endpoint of an improvement of Overall Survival (OS) was not met....The majority of patients were already progressive before or during the first 3 bi-weekly injections, as evidenced by the CT scan performed after the third injection. As such, the first injections were administered too late, as MesoPher cannot exert its effects in progressive patients....In addition, both arms performed well with a median OS around 18 months after randomization, potentially due to the second-line therapy with checkpoint inhibitors."

P2/3 data • Mesothelioma • Oncology • Solid Tumor

ENSURE: Dendritic cell therapy (MesoPher) in combination with extended-pleurectomy/decortication after chemotherapy in subjects with resectable mesothelioma: A feasibility study (ESMO 2022) - P1 | "Tumor-specific immune activation will be investigated using both tumor material and peripheral blood samples prior and post DCT with flow cytometry, imaging mass cytometry, and T-cell receptor repertoire analysis. The trial is active at the Erasmus MC, Rotterdam (NL), enrolling patients since January 2022."

Clinical • Combination therapy • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor

Last patient completed follow-up period in Phase II/III study of Amphera’s MesoPher cell therapy in mesothelioma (Businesswire) - "Amphera B.V...announces that the last patient has completed the active follow-up in the Phase II/III DENIM study of MesoPher cell therapy to treat pleural mesothelioma....'We plan to report topline results early in Q4 2022. The results are expected to be the basis for an EMA Marketing Authorization Application in H1 2023, starting the process of bringing this new therapy to mesothelioma patients'....In Q4 2022, Amphera will also present the survival data of the expansion cohort of 28 patients in the Phase II REACtiVe study of MesoPher in resected pancreatic cancer."

European regulatory • P2 data • P2/3 data • Trial status • Gastrointestinal Cancer • Malignant Pleural Mesothelioma • Oncology • Pancreatic Cancer • Solid Tumor

Amphera’s MesoPher Cell Therapy Demonstrates Favourable Safety and Promising Survival in a Phase II Clinical Trial in Resected Pancreatic Cancer (Businesswire) - P2 | N=26 | "Amphera B.V. announces positive REACtiVe Phase 2 study safety and efficacy data from the first cohort of 10 patients receiving Amphera’s MesoPher dendritic cell therapy. Patients, with resected pancreatic cancer who had completed standard-of-care chemotherapy, received 3 bi-weekly injections of MesoPher and booster injections at 4 and 7 months....The latest REACtiVe data showed an average Overall Survival after surgery of approximately 36 months, with 8 of 10 patients alive, which is far beyond expected survival."

P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

ENSURE: dENdritic Cell Therapy Combined With SURgEry in Mesothelioma (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Erasmus Medical Center

Combination therapy • New P1 trial • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor

Amphera progresses two pancreatic cancer programmes after encouraging initial safety and efficacy data in mesothelioma (Businesswire) - "Amphera B.V...announces significant progress in its two clinical programs in pancreatic cancer as well as the full recruitment of all patients in its pivotal Phase II/III study in mesothelioma. Based on a preliminary efficacy analysis of the first cohort of the REACtiVe study in resected pancreatic cancer patients, an expansion cohort has been completed at a remarkable pace with results expected in H2 2022...In addition a study in metastatic pancreatic cancer, REACtiVe-2, has started recruiting patients....Finally, the company announces that the Phase II/III pivotal study DENIM in mesothelioma patients is fully recruited and confirms the readout to be expected in Q4 2022."

Enrollment status • P2/3 data • Gastrointestinal Cancer • Lung Cancer • Mesothelioma • Oncology • Pancreatic Cancer

Alligator Bioscience Announces Commencement of Investigator Initiated Phase I Clinical Trial at Erasmus University Rotterdam - “Alligator Bioscience…announced the initiation of a proof-of-concept Phase Ib clinical trial to assess the safety and efficacy of mitazalimab in combination with MesoPher, an experimental dendritic cell vaccine, in patients with pancreatic cancer. The trial will be led by investigators at Erasmus MC University Medical Center Rotterdam, The Netherlands. The first patient has been dosed in the phase I proof-of-concept study trial, REACtiVe-2, that will enroll up to 18 patients with pancreatic cancer. REACtiVe-2 will assess the safety and efficacy of Alligator´s second generation CD40 agonist, mitazalimab in combination with the investigational cancer vaccine MesoPher, which is comprised of autologous dendritic cells loaded with allogeneic tumor lysate (PheraLys), in patients with progressive metastatic pancreatic cancer.”

Trial status • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

[VIRTUAL] Long-term follow up of patients with mesothelioma treated with dendritic cell therapy in three phase I trials. (ASCO 2021) - P1, P2/3 | "In the first two trials, DCs loaded with autologous tumor lysate were used, while in the third allogeneic tumor lysate was used to load the DCs (Mesopher)... The long-term follow up of MPM patients treated with DC vaccination in the three separate phase 1 trials show a promising signal, with a 2-year OS of over 50% and a 5-year OS of over 20% . In addition, 2 patients are alive after 10 years of treatment . In our opinion, these findings show the potency of DC vaccination therapy in long-term activation of the immune system ."

Clinical • IO biomarker • P1 data • Gastrointestinal Cancer • Hepatology • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pancreatic Cancer • Solid Tumor

DENIM: DENdritic Cell Immunotherapy for Mesothelioma (clinicaltrials.gov) - P2/3; N=230; Recruiting; Sponsor: Amphera BV; Trial completion date: Jan 2021 ➔ Feb 2023; Trial primary completion date: Jan 2021 ➔ Feb 2023

Clinical • Trial completion date • Trial primary completion date • Lung Cancer • Mesothelioma • Oncology • Solid Tumor