LM-101 was well tolerated. The preliminary efficacy signal supports further evaluation of LM-101 plus rituximab in relapsed/refractory lymphoma.

In vivo, RRx-001 significantly inhibits tumor growth, enhances T-cell infiltration, promotes M1 macrophage polarization, downregulates PD-L1 expression, and strengthens anti-tumor immunity through T cell-related pathways. With both metabolic and immunomodulatory effects, RRx-001 provides a basis for novel HCC therapies, and future research could explore its synergistic effects with immune checkpoint inhibitors.

Nanoprodrugs orchestrate a sophisticated cascade of immune activation through four synergistic mechanisms: 1) size-switchable disassembly upon glutathione/ cholesterol exposure for deep tumor penetration; 2) redox imbalance driven by reactive nitrogen species accumulation and glutathione depletion via the synergistic action of oxaliplatin, ferrocene, and RRx-001 for ferroptosis augmentation; 3) immunogenic cell death induction via ferroptosis-apoptosis to initiate tumor immunity cycle, promoting T cell infiltration; and 4) T cell function reinvigoration with the downregulation of programmed cell death protein 1 and T-cell immunoglobulin 3 expression through cholesterol depletion in TME. This integrated approach achieved primary and distant tumor growth suppression, established durable immune memory against recurrence, and systemically enhanced the antitumor immunity. By concurrently targeting tumor immunogenicity, TME immunosuppression, and T cell exhaustion, this multidimensional strategy represents a transformative advancement in cancer immunotherapy.

In conclusion, this study systematically characterizes the clinical and immunological associations of CD47 across multiple cancers and highlights its potential role in pancreatic adenocarcinoma, supporting the further investigation of CD47 as a therapeutic target.

P2, N=28, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed

P1, N=14, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

In this study, we propose a Gas-Metal Synergy Strategy, which integrates immune activation and biosafety, by engineering a pH-responsive manganese-based zeolitic imidazolate framework (named MRPH) nanoplatform co-loaded with the nitric oxide (NO) donor RRX-001...Both in vitro and in vivo studies demonstrate that MRPH significantly enhances gas-amplified metalloimmunotherapy. This work pioneers a low-toxicity paradigm that integrates gas therapy and metal-based immunotherapy, offering a transformative approach to solid tumor immunotherapy.

P1, N=130, Recruiting, Sairopa B.V. | N=90 --> 130 | Trial completion date: Dec 2025 --> Jul 2027 | Trial primary completion date: Dec 2025 --> May 2027

P1, N=20, Terminated, Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd. | N=43 --> 20 | Trial completion date: Feb 2026 --> Jun 2025 | Recruiting --> Terminated | Trial primary completion date: Oct 2025 --> Jun 2025; This study was closed due to business reasons. Closure was not prompted by any safety or efficacy concerns.

P1, N=90, Recruiting, Boehringer Ingelheim | Trial completion date: Mar 2028 --> Jul 2027 | Trial primary completion date: Jul 2027 --> Oct 2026

P1, N=56, Terminated, Bristol-Myers Squibb | Completed --> Terminated; Business objectives have changed

To further counter immune evasion, we encapsulated the CD47/SIRPα inhibitor RRX-001 into reactive oxygen species (ROS)-responsive carriers, yielding RRX@RCD...In CT26 tumor-bearing mice, RRX@RCD achieved superior tumor regression, doubled median survival. Overall, RRX@RCD synchronizes innate and adaptive immune activation, offering a safe and potent nanomedicine strategy for durable antitumor immunity.