Dataset Information

A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors.

ABSTRACT: Over two decades, most cancer vaccines failed clinical development. Key factors may be the lack of efficient priming with tumor-specific antigens and strong immunostimulatory signals. MVX-ONCO-1, a personalized cell-based cancer immunotherapy, addresses these critical steps utilizing clinical-grade material to replicate a successful combination seen in experimental models: inactivated patient's own tumor cells, providing the widest cancer-specific antigen repertoire and a standardized, sustained, local delivery over days of a potent adjuvant achieved by encapsulated cell technology. We conducted an open-label, single-arm, first-in-human phase I study with MVX-ONCO-1 in patients with advanced refractory solid cancer. MVX-ONCO-1 comprises irradiated autologous tumor cells coimplanted with two macrocapsules containing genetically engineered cells producing granulocyte-macrophage colony-stimulating factor. Patients received six immunizations over 9 weeks without maintenance therapy. Primary objectives were safety, tolerability, and feasibility, whereas secondary objectives focused on efficacy and immune monitoring. Data from 34 patients demonstrated safety and feasibility with minor issues. Adverse events included one serious adverse event possibly related to investigational medicinal product and two moderate-related adverse events. More than 50% of the patients with advanced and mainly nonimmunogenic tumors showed clinical benefits, including partial responses, stable diseases, and prolonged survival. In recurrent/metastatic head and neck squamous cell carcinoma, one patient achieved a partial response, whereas another survived for more than 7 years without anticancer therapy for over 5 years. MVX-ONCO-1 is safe, well tolerated, and beneficial across several tumor types. Ongoing phase IIa trials target patients with advanced recurrent/metastatic head and neck squamous cell carcinoma after initial systemic therapy.

Significance

This first-in-human phase I study introduces a groundbreaking approach to personalized cancer immunotherapy, addressing limitations of traditional strategies. By combining autologous irradiated tumor cells as a source of patient-specific antigens and utilizing encapsulated cell technology for localized, sustained delivery of granulocyte-macrophage colony-stimulating factor as an adjuvant, the study shows a very good safety and feasibility profile. This innovative approach holds the promise of addressing tumor heterogeneity by taking advantage of each patient's antigenic repertoire.

SUBMITTER: Vernet R

PROVIDER: S-EPMC11322805 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors.

Vernet Rémi R Fernandez Eugenio E Migliorini Denis D Ancrenaz Virginie V Charrier Emily E Belkouch Marie-Claude MC Von Rohr Olivier O Urwyler Muriel M De Vito Claudio C Renaux Jessica J Villard Jean J Rubin Olivier O Grogg Julien J Mach Nicolas N

Cancer research communications 20240801 8

Over two decades, most cancer vaccines failed clinical development. Key factors may be the lack of efficient priming with tumor-specific antigens and strong immunostimulatory signals. MVX-ONCO-1, a personalized cell-based cancer immunotherapy, addresses these critical steps utilizing clinical-grade material to replicate a successful combination seen in experimental models: inactivated patient's own tumor cells, providing the widest cancer-specific antigen repertoire and a standardized, sustained ...[more]

PMID: 39041242

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Project description:Definitive management of locoregionally advanced solid tumors presents a major challenge and often consists of a combination of surgical, radiotherapeutic and systemic therapy approaches. Upfront surgical treatment with or without adjuvant radiotherapy carries the risks of significant morbidities and potential complications that could be lasting. In addition, these patients continue to have a high risk of local or distant disease relapse despite the use of standard adjuvant therapy. Preoperative neoadjuvant systemic therapy has the potential to significantly improve clinical outcomes, particularly in this era of expanding immunotherapeutic agents that have transformed the care of patients with metastatic/unresectable malignancies. Tremendous progress has been made with neoadjuvant immunotherapy in the treatment of several locoregionally advanced resectable solid tumors leading to ongoing phase 3 trials and change in clinical practice. The promise of neoadjuvant immunotherapy has been supported by the high pathologic tumor response rates in early trials as well as the durability of these responses making cure a more achievable potential outcome compared with other forms of systemic therapy. Furthermore, neoadjuvant studies allow the assessment of radiologic and pathological responses and the access to biospecimens before and during systemic therapy. Pathological responses may guide future treatment decisions, and biospecimens allow the conduct of mechanistic and biomarker studies that may guide future drug development. On behalf of the National Cancer Institute Early Drug Development Neoadjuvant Immunotherapy Working Group, this article summarizes the current state of neoadjuvant immunotherapy of solid tumors focusing primarily on locoregionally advanced melanoma, gynecologic malignancies, gastrointestinal malignancies, non-small cell lung cancer and head and neck cancer including recent advances and our expert recommendations related to future neoadjuvant trial designs and associated clinical and translational research questions.

Project description:BackgroundRecent genomic and bioinformatic technological advances have made it possible to dissect the immune response to personalized neoantigens encoded by tumor-specific mutations. However, timely and efficient identification of neoantigens is still one of the major obstacles to using personalized neoantigen-based cancer immunotherapy.MethodsTwo different pipelines of neoantigens identification were established in this study: (1) Clinical grade targeted sequencing was performed in patients with refractory solid tumor, and mutant peptides with high variant allele frequency and predicted high HLA-binding affinity were de novo synthesized. (2) An inventory-shared neoantigen peptide library of common solid tumors was constructed, and patients' hotspot mutations were matched to the neoantigen peptide library. The candidate neoepitopes were identified by recalling memory T-cell responses in vitro. Subsequently, neoantigen-loaded dendritic cell vaccines and neoantigen-reactive T cells were generated for personalized immunotherapy in six patients.ResultsImmunogenic neo-epitopes were recognized by autologous T cells in 3 of 4 patients who utilized the de novo synthesis mode and in 6 of 13 patients who performed shared neoantigen peptide library, respectively. A metastatic thymoma patient achieved a complete and durable response beyond 29 months after treatment. Immune-related partial response was observed in another patient with metastatic pancreatic cancer. The remaining four patients achieved the prolonged stabilization of disease with a median PFS of 8.6 months.ConclusionsThe current study provided feasible pipelines for neoantigen identification. Implementing these strategies to individually tailor neoantigens could facilitate the neoantigen-based translational immunotherapy research.TRIAL REGSITRATION. ChiCTR.org ChiCTR-OIC-16010092, ChiCTR-OIC-17011275, ChiCTR-OIC-17011913; ClinicalTrials.gov NCT03171220.FundingThis work was funded by grants from the National Key Research and Development Program of China (Grant No. 2017YFC1308900), the National Major Projects for "Major New Drugs Innovation and Development" (Grant No.2018ZX09301048-003), the National Natural Science Foundation of China (Grant No. 81672367, 81572329, 81572601), and the Key Research and Development Program of Jiangsu Province (No. BE2017607).

Dataset Information

A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors.

Significance

Publications

A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors.

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