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The Bi-steric, mTORC1-Selective Inhibitor, RMC-5552, in Advanced Solid Tumors: A Phase 1 Trial

Schram AM, Naqash AR, Haura EB, Riess JW, Ulahannan SV, Ou SI, Munster PN, Cheng ML, Gustafson WC, Bitman B, Friedman R, …, Meyerowitz JG · 2025 · Clinical Cancer Research · Atlas ID SCH2025

What this study shows

First-in-human, open-label dose-escalation trial (n=57, advanced solid tumors, no comparator arm) of a bi-steric mTORC1-selective inhibitor. Treatment-related hyperglycemia was low (4%) and not dose-limiting, alongside a 64% disease control rate. Because the trial was uncontrolled and made no head-to-head comparison against rapamycin or an ATP-site inhibitor, this is encouraging early clinical evidence consistent with the hypothesis that sparing mTORC2 reduces metabolic toxicity -- it does not establish mTORC2 sparing as the cause.

Cited on mTOR drugs in development: RMC-5552

Abstract

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PI3K/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).

Read the full abstract on PubMed →

At a glance

Evidence type H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type2 - Human Clinical Trial
Model systemHuman (Phase 1 dose escalation, n=57, advanced solid tumors, NCT04774952)
JournalClinical Cancer Research
Year2025
Peer reviewedYes
Record last updated2026-07-29
SourceDOI 10.1158/1078-0432.CCR-25-2112 · PMID 41056387 · Free full text (PMC12666311)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

InterventionRMC-5552 (bi-steric mTORC1-selective inhibitor), 1.6-16mg IV weekly
TargetmTORC1 (4E-BP1, S6K1), sparing mTORC2
ModelHuman
Effect64% disease control rate (uncontrolled); low (4%) treatment-related hyperglycemia, consistent with mTORC2 sparing

In the Atlas

Related topics

Bi-steric mTORC1-selective inhibitorsmTORC1mTORC2S6K14E-BP1

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Learn the biology

Want to understand the biology behind this study? → Challenge 02: Why rapamycin does not switch mTORC1 off

Cite this paper

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Schram, A. M., Naqash, A. R., Haura, E. B., Riess, J. W., Ulahannan, S. V., Ou, S. I., Munster, P. N., Cheng, M. L., Gustafson, W. C., Bitman, B., Friedman, R., Penn, R., Kar, S., Seshadri, V., Wang, Z., Tao, L., Yang, Y. C., Singh, M., Burris, H. A., & Meyerowitz, J. G. (2025). The Bi-steric, mTORC1-Selective Inhibitor, RMC-5552, in Advanced Solid Tumors: A Phase 1 Trial. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-25-2112

@article{SCH2025,
  author       = {Schram, A. M. and Naqash, A. R. and Haura, E. B. and Riess, J. W. and Ulahannan, S. V. and Ou, S. I. and Munster, P. N. and Cheng, M. L. and Gustafson, W. C. and Bitman, B. and Friedman, R. and Penn, R. and Kar, S. and Seshadri, V. and Wang, Z. and Tao, L. and Yang, Y. C. and Singh, M. and Burris, H. A. and Meyerowitz, J. G.},
  title        = {{The Bi-steric, mTORC1-Selective Inhibitor, RMC-5552, in Advanced Solid Tumors: A Phase 1 Trial}},
  journal      = {Clinical Cancer Research},
  year         = {2025},
  doi          = {10.1158/1078-0432.CCR-25-2112},
  note         = {PMID: 41056387},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper. 

Barton, O. (2026). Oliver's mTOR Atlas (record SCH2025) [Data set]. https://mtor-atlas.org/study/SCH2025/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SCH2025,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SCH2025},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SCH2025/},
  doi          = {10.5281/zenodo.22059963}
}
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