Generating CAR-T Cells Inside Patients: Phase 1 PICX Trial Launches in Multiple Myeloma

Patients with relapsed or refractory multiple myeloma may experience further disease progression even after multiple lines of treatment. Chongqing Precision Biotech Co., Ltd. has now advanced PICX Injection, an “in vivo–prepared” CAR-T therapy, into human testing in an effort to find a more direct treatment pathway beyond existing cell therapy models.

This Phase 1 trial in China, numbered NCT07715630, uses a prospective, open-label, single-arm design and is expected to enroll 15 adults at a single center. Participants will receive a single intravenous infusion, followed by hospitalization for close observation. The study’s initial aim is to determine tolerable doses and short-term safety, rather than compare efficacy with existing therapies.

Conventional autologous CAR-T therapy generally requires collecting a patient’s T cells, genetically modifying, expanding, and quality-testing them ex vivo, and then infusing them back into the patient. The concept of in vivo–prepared CAR-T is to have the cellular modifications required for treatment occur inside the patient. If feasible, it could shorten the manufacturing process and reduce reliance on specialized cell manufacturing facilities in the future. However, the trial registration has not yet specified which delivery system PICX uses, how the genetic modification is controlled, or its molecular target. It is therefore not currently possible to determine how it substantively differs from existing CAR-T therapies for multiple myeloma.

The trial’s primary observation period is the first 28 days after infusion. Researchers will record dose-limiting toxicities, adverse events, and serious adverse events to estimate the maximum tolerated dose. Subsequent endpoints include objective response rate, minimal residual disease negativity rate, time to response and duration of response, as well as progression-free survival and overall survival. Follow-up will last up to two years, and the primary study phase is expected to be completed in April 2028.

Eligibility criteria include patients whose disease has progressed after at least two standard regimens, who experienced progression within 18 months after first-line treatment, or who have features associated with a high risk of relapse. Patients who previously received CAR-T or other genetically modified cell therapies are excluded. The study also sets restrictions related to infection, recent anticancer treatment, and certain heart diseases to reduce uncertainty during early-stage dose exploration.

The significance of this study is that generating CAR-T cells in vivo is moving from a technical concept toward small-scale clinical validation; it is not yet evidence of a breakthrough in efficacy. A single-center, uncontrolled trial involving only 15 people can primarily determine whether PICX can be administered as planned, whether its short-term toxicity is acceptable, and which doses warrant further study. The durable efficacy, rare risks, manufacturing consistency, and scalability that will ultimately determine its clinical value will require full technical disclosure and larger trials.