CREATE Medicines Initiates First In Vivo CAR Therapy Trial in Frontline Gastroesophageal Cancer Treatment
核心洞察
CREATE Medicines (搜索) and Amsterdam University Medical Center (搜索) have dosed the first patient in the SPaCE-MT trial, marking the first clinical evaluation of an in vivo CAR therapy combined with standard frontline treatment for solid tumors.
The trial evaluates MT-302, a TROP2 (搜索)-targeting mRNA-LNP therapy, in combination with capecitabine, oxaliplatin (CAPOX) with or without nivolumab or trastuzumab for advanced gastroesophageal cancer (搜索).
CREATE has generated one of the largest clinical datasets in the in vivo CAR field with over 200 monotherapy doses administered, demonstrating proof-of-mechanism, manageable safety profile, and evidence of activity including a confirmed partial response lasting 16 months.
CREATE Medicines (搜索) Inc, formerly Myeloid Therapeutics Inc, has achieved a significant milestone in cancer immunotherapy by dosing the first patient in a groundbreaking clinical trial that combines in vivo CAR therapy with standard frontline treatment for solid tumors. Amsterdam University Medical Center (搜索) (Amsterdam UMC) administered the first dose in the SPaCE-MT clinical trial, which evaluates CREATE's MT-302 therapy alongside established chemotherapy regimens for advanced gastroesophageal cancer (搜索).
Pioneering In Vivo CAR Therapy Approach
The SPaCE-MT trial represents the first clinical evaluation of an in vivo CAR therapy combined with a standard frontline regimen for solid tumors. MT-302, a TROP2 (搜索)-targeting mRNA-LNP in vivo CAR therapy, will be administered with capecitabine, oxaliplatin (CAPOX) with or without nivolumab or trastuzumab in patients with advanced gastroesophageal cancer (搜索).
"In vivo mRNA CARs represent a new class of programmable medicines, and SPaCE–MT brings this modality into frontline care. The early MT–302 data demonstrate safety and activity that support combination therapy – expanding options and meaningfully improving outcomes for patients," said Daniel Getts, chief executive officer of CREATE Medicines (搜索).
Clinical Validation and Safety Profile
CREATE has distinguished itself by generating one of the largest clinical datasets in the in vivo CAR field across multiple phase 1 studies. The company has demonstrated compelling clinical validation through three key areas:
Proof-of-mechanism: Paired biopsies confirmed CAR+ immune cells infiltrating tumors, with immune remodeling and CD8 T-cell recruitment.
Safety data and repeat dosing: Over 200 monotherapy doses have been administered with a consistent, manageable safety profile and no cumulative toxicities observed to date.
Evidence of activity: CAR expression was detected in circulating immune cells, stable disease was observed in several patients, and a confirmed partial response lasting 16 months was achieved.
Addressing Critical Medical Need
Gastroesophageal cancers represent a significant global health burden, with over 1.3 million new cases diagnosed globally each year. These cancers remain a leading cause of cancer-related mortality worldwide. While progress has been made with chemotherapy, targeted agents, and immune checkpoint inhibitors, outcomes for patients with advanced gastroesophageal cancer (搜索) remain poor, and resistance to frontline therapies is common.
"The initiation of this study underscores the need for innovative treatment strategies in gastroesophageal cancer (搜索), where outcomes still remain very poor," said Matt Maurer, chief medical officer, CREATE Medicines (搜索). "By combining our in vivo CAR therapy with established chemotherapeutic and immunotherapy treatments, we aim to unlock the full potential of a coordinated immune attack against cancer."
Novel Therapeutic Mechanism
MT-302 is a first-in-class, TROP2 (搜索)-FcA-LNP therapy that programs immune cells directly in vivo to attack tumors. TROP2 is overexpressed in most epithelial cancers (搜索), with limited expression in normal tissues. Unlike antibody-drug conjugates, MT-302 elicits a coordinated immune response by engaging innate and adaptive arms, including presentation of tumor neoantigens to T cells.
Professor Hanneke van Laarhoven, leading scientist on the trial and medical oncologist and head of the department of medical oncology at Amsterdam UMC - Cancer Center, recognizes that MT-302 has significant potential to enhance frontline therapy and improve outcomes for patients with advanced esophageal and gastric cancers.
Trial Design and Future Implications
SPaCE-MT (Safety and Preliminary Clinical Efficacy of MT-302 with CAPOX-based Regimens in Metastatic Esophagogastric Cancer, EUCT 2024-520213-45-00) is an open-label, Phase 1/2 investigator-initiated trial. The study evaluates the safety, tolerability, and preliminary efficacy of MT-302 in combination with CAPOX with or without nivolumab or trastuzumab in patients with advanced gastroesophageal cancer (搜索).
In vivo CAR therapies have become one of the most closely watched frontiers in oncology, offering the potential to overcome the manufacturing complexity, cost, and scalability limitations of traditional ex vivo CAR-T approaches. This trial marks a pivotal step in advancing in vivo immune programming to unlock truly scalable, off-the-shelf cell therapies through repeat-dose treatments that expand access and integrate seamlessly with existing standards of care.