ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
The Bi-steric, mTORC1-Selective Inhibitor, RMC-5552, in Advanced Solid Tumors: A Phase 1 Trial.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04774952 (A Phase 1/1b, Open-Label, Multicenter, Dose-Escalation Study of RMC 5552 Monotherapy in Adult Subjects With Relapsed/Refractory Solid Tumors), which is not on this map. Cited by 5 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1/1b, Open-Label, Multicenter, Dose-Escalation Study of RMC 5552 Monotherapy in Adult Subjects With Relapsed/Refractory Solid Tumors
Who cites it
5 citing papers in PubMed.
- A design approach for bitopic kinase inhibitors.Nature · 2026Article
- A renaissance in targeting the PI3K/AKT/mTOR pathway.Nature reviews. Drug discovery · 2026Review
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- RMC-6272, a selective third-generation bi-steric mTORC1 inhibitor, improves cardiac function in pressure overload-induced cardiac hypertrophy.Journal of molecular and cellular cardiology plus · 2026Article
- Viral-host interactions mediated by the mTOR signaling pathway.Cell insight · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
purposePI3K/mTOR pathway activation drives oncogenesis and progression of many cancers. RMC-5552 is a bi-steric, mTOR complex 1 (mTORC1)-selective inhibitor that potently inhibits phosphorylation of key mTORC1 substrates eukaryotic initiation factor 4E-binding protein-1 and S6 kinase and exhibits selectivity for mTORC1 over mTORC2. In this study, we report results from a first-in-human, dose-escalation study of RMC-5552 in patients with advanced solid tumors (NCT04774952). PATIENTS AND
methodsThe safety, tolerability, pharmacokinetics, and preliminary activity of RMC-5552 (1.6-16 mg intravenous infusion weekly) were evaluated in 57 patients.
resultsThe most common treatment-related adverse events were mucositis (49%), nausea (44%), and fatigue (42%). Consistent with mTORC1 selectivity, treatment-related hyperglycemia incidence was generally low (4%) and not dose limiting. Additionally, we tested potential prophylaxis with tacrolimus mouthwash (TM), which was predicted to block the mechanism of action of RMC-5552 locally and alleviate treatment-related oral mucositis. Between 8- and 12-mg dosing, mucositis was 65% without TM versus 31% with TM. In this study, the disease control rate was 64%, and one patient with PTEN- and PIK3CA-altered endometrial cancer had a complete response and treatment was ongoing for >6 months as of the June 2024 data cut. Clearance of PI3K/mTOR pathway variants among ctDNA was observed.
conclusionsThe success of TM-mediated prophylaxis and the clearance of selected variants in ctDNA are concordant with selective, on-mechanism, antitumor activity following RMC-5552 treatment. These data show that RMC-5552, the first bi-steric mTORC1-selective inhibitor in the clinic, is active at tolerable doses and that selective inhibition of mTORC1 alleviates mTORC2-mediated hyperglycemia, overcoming a key limitation of prior mTOR inhibitors.
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